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2023 Vol. 14, No. 5

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Editorials
Metagenomic Next-generation Sequencing: Current Status, Challenges and Prospects of Clinical Application
DIAO Zhenli, LI Jinming
2023, 14(5): 905-910. doi: 10.12290/xhyxzz.2023-0089
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Traditional microbial detection methods have difficulty meeting the needs of pathogen detection in the clinic. In recent years, metagenomic next-generation sequencing (mNGS) technology has emerged and been widely used in the diagnosis of various infectious diseases, the etiological analysis of emerging infectious diseases, the detection of drug resistance genes and the analysis of the host immune response. However, the mNGS workflow is complicated, and the variation introduced in each step will influence the accuracy of the detection results. In addition, the absence of standardized methods, the lack of personnel knowledge and ability, and the high cost of instruments and reagents are also creating main obstacles to the clinical application of mNGS. Therefore, standardization and normalization of methods as well as improvement of personnel knowledge and ability are urgently needed for mNGS detection. The integration of pathogen, transcriptome and antibiotic resistance genes information to comprehensively improve the clinical management of patients with infectious diseases is an important direction of mNGS detection.
Castleman Disease in China: State-of-the-art Technology Before the Era of IL-6 Targeted Therapy
ZHANG Lu, LI Jian
2023, 14(5): 911-914. doi: 10.12290/xhyxzz.2023-0227
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Castleman disease (CD) is a group of rare and heterogenous hematological diseases included in the 'Rare disease catalogue' of China. Among the different clinical subtypes of CD, idiopathic multicentric Castleman disease (iMCD) is characterized by symptomatic inflammatory symptoms with poor prognosis. Interleukin-6 (IL-6) targeted therapy (eg. siltuximab) is now considered as the most important treatment option according to international and domestic treatment guidelines and consensus. On July 2022, siltuximab became available in Chinese market, heralding the era of IL-6 targeted therapy in China. Thus, it is a good time point to review the state-of-the-art technology in the field of diagnosis and treatment of CD. We also highlight some of the clinical investigations conducted by Chinese researchers.
Specialist Forum
Mechanism of Bacterial Extracellular Vesicles in Disease Development and Prospects for Application
LUO Xiaoxia, QIN Sihua, WANG Huidi, ZHOU Hongwei, HE Yan
2023, 14(5): 915-924. doi: 10.12290/xhyxzz.2023-0260
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Bacterial extracellular vesicles (BEVs), bacteria-derived extracellular vesicles, are key intermediates of bacteria-bacteria and bacteria-host interactions. They are a "double-edged sword". On one hand, they play a negative role in the onset and progression of various diseases, including intestinal inflammatory disease, neurological disease, liver disease, metabolic disease, autoimmune disease and cancer. On the other hand, they play a positive role as potential biomarkers, vaccines, antitumor agents. The application of BEVs may provide novel strategies for the diagnosis and treatment of diseases. However, research on BEVs is still in its infancy, and challenges remain in vesicle isolation techniques, disease diagnostic specificity, optimization of vesicle storage and transport. Thus rigorously designed clinical studies are required to verify their diagnostic and therapeutic value.
Research Progress on the Mechanism of Infection in Autoimmune Diseases
CHENG Linlin, LI Zhan, LI Yongzhe
2023, 14(5): 925-931. doi: 10.12290/xhyxzz.2023-0268
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The pathogenesis of autoimmune diseases (AID) is a complex process. In recent years, an increasing number of evidence has shown that infection plays a key role in driving the occurrence and progression of AID, particularly in individuals with underlying genetic predisposition. This provides a new and broader perspective for clinical examination of the causes and potential mechanisms of AID. In this review, we aim to summarize the latest research progress on the relationship between pathogenic microorganisms and autoimmunity/AID, with the goal of exploring the etiology and pathogenesis of common AID from an etiological perspective. By integrating existing evidence, we hope to deepen the understanding of AID pathogenesis and provide valuable insights for disease prevention, clinical diagnosis and treatment.
Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug
WANG Na, HAN Xiaohong
2023, 14(5): 932-938. doi: 10.12290/xhyxzz.2023-0212
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Despite the rapid development of antitumor drugs, the limited drug response rate and adverse drug reactions have severely limited their clinical application. In recent years, the concept of "pharmacomicrobiomics" has emerged, and more and more studies have shown thatmicrobiota plays an important role in the treatment of antitumor drugs. Herein, the interaction between microbiota and antitumor drugs is reviewed from the aspects of chemotherapeutics, molecular targeted drugs and immunotherapy drugs. The mechanism involves immune regulation, hormone regulation, metabolite regulation, drug biotransformation and transmembrane transport regulation. The microbiota regulation strategies that can improve the efficacy and reduce adverse reactions of antitumor drugs are reviewed, in order to provide reference for the individualized treatment of clinical antitumor drugs.
The Impact of Gut Microbiota on Vaccine Immune Efficacy and Potential Mechanisms
HUANG Biqing, LI Lanjuan
2023, 14(5): 939-944. doi: 10.12290/xhyxzz.2023-0173
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Vaccine is the most effective method to prevent the spread of communicable diseases, but the immune response it induces varies significantly among individuals and populations in different regions. Recent studies have shown that the composition and function of the gut microbiota play a key role in the immune response following vaccination. This article aims to explain the differences in gut microbiota among different vaccinated populations and animals, discuss how the gut microbiota affects the immune efficacy of the vaccine, and summarize strategies for targeting the gut microbiota to improve vaccine efficacy.
Virological Characteristics of the Omicron Variant: Key Mutations, Pathogenicity, and Immune Escape
CHEN Yuqing, LI Jinming
2023, 14(5): 945-952. doi: 10.12290/xhyxzz.2023-0139
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was first detected in Botswana and subsequently led to a worldwide surge in infections. Until now, Omicron and its lineages, the most highly mutated strains among variants of concern (VOC), have contained at least 50 mutations in the entire genome. Mutations give the virus certain adaptive advantages, such as the enhanced affinity between receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptors leading to enhanced transmission of the virus, and the weakened ability of virus replication leading to mild symptoms in patients with COVID-19. In addition, given its high environmental stability, Omicron can partially escape the host immune response induced by vaccination or prior infection, and is highly resistant tomost therapeutic antibodies.In this paper, key mutations, virological characteristics, pathogenicity, and immune escape of the Omicron variant are summarized, in order to provide scientific reference for coping with the new situation of the pandemic, as well as improving pandemic prevention and control strategy and public health measures.
Research Progress of the Impact of SARS-CoV-2 on Fertility
ZHANG Kezhen, JIN Li
2023, 14(5): 953-958. doi: 10.12290/xhyxzz.2023-0289
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The COVID-19 pandemic caused by SARS-CoV-2 has brought great challenges to all countries. SARS-CoV-2 infection can bring damage to multiple organs of the human body. The impact of SARS-CoV-2 on fertility has become a focus of interest. This article reviews the mechanism of SARS-CoV-2 attacking the human body, and its impact on fertility, pregnancy and assisted reproductive technique, with the hope of providing reference for clinicians.
Guideline and Consensus
Expert Consensus on Nucleic Acid of Amplification Techniques Test for the Diagnosis of Pathogens in Adult Respiratory Tract Infections(2023)
The Committee of Chinese Laboratory Medical Education, Chinese Thoracic Society of the Chinese Medical Association
2023, 14(5): 959-971. doi: 10.12290/xhyxzz.2023-0338
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Respiratory tract infection is one of the most prevalent medical conditions. Rapid and accurate diagnosis of pathogens is crucial for precise and effective treatment. However, the sensitivity of traditional microbiological and immunological techniques for respiratory pathogens detection is low.The development and clinical applications of nucleic acid testing technology have dramatically improved the ability to diagnose respiratory pathogens. The rational usage of appropriate nucleic acid testing techniques, based on the underlying diseases, the type of respiratory tract infections, and pathogen spectrum, as well as the correct understanding of its diagnostic sig- nificance, has become an important clinical challenge. Therefore, the Committee of Chinese Laboratory Medical Education and Chinese Thoracic Society initiated a multi-disciplinary Chinese expert consensus. Based on both the domestic and international guidelines and literature, the expert consensus analyzes the clinical application scenarios, technical characteristics, and performance validation requirements pertaining to real-time fluorescence polymerase chain reaction (PCR), isothermal amplification technology, digital PCR, nucleic acid point-of-care testing, and metagenomics next generation sequencing. Furthermore, it also examines the wide-ranging applications of these techniques in diagnosing and managing respiratory tract infections, including acute upper respiratory tract infections, tracheobronchitis, community-acquired pneumonia, hospital-acquired pneumonia/ventilator-associated pneumonia, acute exacerbation of chronic obstructive pulmonary disease, tuberculosis, and respiratory infections in immunocompromised adults. We hope the consensus will provide helpful reference for clinicians.
Expert Consensus on Clinical Specimen Preservation and Biosafety Protection in the Context of Managing COVID-19 with Measures against Class B Infectious Diseases
Clinical Data and Biobank Committee of China Research Hospital Association, Guangdong Human Genetic Resource Biobanking and Applications Association
2023, 14(5): 972-977. doi: 10.12290/xhyxzz.2023-0258
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During the past three years, the national prevention and control policies for coronavirus disease 2019(COVID-19) have gone from"Class A control" to "Class B control". Therefore, it is necessary to reexamine the biosafety risks, carry out corresponding biosafety protection practices, and formulate management measures for clinical Biobank when conducting sample preservation activities. It is imperative to improve the biosafety protection system in view of the constantly mutating characteristics and potential risks of novel coronavirus. Professional Committee of Clinical Data and Sample Resource Database of China Research Hospital Association and the Human Genetic Resource Conservation and Application Society of Guangdong Province jointly drafted and formulated this consensus. We aim to provide practical guidance on biosafety protection for sample preservation activities, reduce biosafety risks, and ensure the safe and efficient implementation of sample preservation activities.
Standard and Specification
Establishment of the Resident Core Competency Milestone Evaluation System in China Consortium of Elite Teaching Hospitals
China Consortium of Elite Teaching Hospitals
2023, 14(5): 978-982. doi: 10.12290/xhyxzz.2022-0543
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China Consortium of Elite Teaching Hospitals (the Consortium) is dedicated to exploring the reform and development of graduate medical education and promoting the training of high-level medical talents in line with international standards and on the basis of standardized residency training.The Consortium has made in-depth efforts in deepening the collaboration of medical practice and medical education, promoting the commitment of competency-based medical education (CBME) and facilitating the establishment of milestone evaluation system. In this paper, the establishment of the Consortium Consensus on Core Competency Framework and the milestone evaluation system are expounded, and the challenges and prospects of the implementation of the competency framework and milestone evaluation system are analyzed. It is concluded that the establishment and implementation of the milestone framework will help the Consortium play a leading role in CBME and promote the overall medical education level in China.
China Healthcare Big Data
Annual Research Progress of Glioma in China in 2022
CHEN Wenlin, WANG Yuekun, LIU Qianshu, YE Liguo, ZHENG Zhiyao, ZHANG Xin, GONG Le, CAO Yaning, SONG Yixuan, GUO Xiaopeng, WANG Yu, MA Wenbin
2023, 14(5): 983-990. doi: 10.12290/xhyxzz.2023-0321
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Glioma, the most prevalent primary malignant tumor of the adult central nervous system, is highly malignant. Despite the current clinical treatment options including surgical resection, radiotherapy and chemotherapy, the survival period of patients is still relatively short, which poses a serious threat to patients' lives and health. In recent years, the research on glioma has made great progress, and the study on the mechanism of glioma development and the characteristics of the immune microenvironment has also deepened. At the same time, researches on molecular pathological typing of glioma, comprehensive clinical diagnostic and therapeutic programs, novel drug delivery systems and big data clinical translation are also steadily underway. This article reviews the research progress in the field of glioma in China in 2022, with the hope of providing reference for clinical diagnosis and treatment.
Original Contributions
Quantitative Analysis of Mitochondrial Damage in T Lymphocytes from Patients with Autoimmune Diseases and Evaluation of Its Clinical Value
WU Ziyan, FENG Futai, LI Haolong, XU Honglin, ZHANG Shulan, LI Yongzhe
2023, 14(5): 991-998. doi: 10.12290/xhyxzz.2023-0256
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  Objective  To evaluate the mitochondrial damage of peripheral blood T lymphocytes in patients with autoimmune diseases (AID) and provide insights for etiological research.  Methods  Clinical data were retrospectively collected from the AID patients treated at the Peking Union Medical College Hospital from March 2023 to April 2023 and from a population that was physically healthy during the same period. Based on the ratio of peripheral blood helper T cells (Th) to cytotoxic T cells (Tc), the AID patients were divided into an immunodeficiency subgroup and an immunocompetent subgroup. Flow cytometry was used to assess the mitochondrial damage of T lymphocytes in the AID patients, with the percentage of cells showing low mitochondrial membrane potential (MMP-low%) as an indicator of mitochondrial dysfunction, and its correlation with AID was analyzed.  Results  A total of 70 AID patients and 20 healthy individuals who met the inclusion and exclusion criteria were included. Among the AID patients, there were 20 immunodeficient cases (Th/Tc ratio < 0.70) and 50 immunocompetent cases (Th/Tc ratio ≥0.70); 33 patients had systemic lupus erythematosus (SLE), 19 had rheumatoid arthritis (RA), and 18 had Sjögren syndrome (SS). The percentage of CD3+ T lymphocytes showing low mitochondrial membrane potential (T MMP-low%), CD3+CD4+ T lymphocytes showing low mitochondrial membrane potential (Th MMP-low%), and CD3+CD8+ T lymphocytes showing low mitochondrial membrane potential (Tc MMP-low%) in SLE, RA, and SS patients were all lower than those in healthy individuals (all P < 0.05). In the AID patients, the percentages of T MMP-low%, Th MMP-low%, and Tc MMP-low% in both the immunodeficient subgroup and immunocompetent subgroup were lower than those in healthy individuals (P < 0.05). Compared to the immunocompetent subgroup, the immunodeficient subgroup showed a decreasing trend in the percentages of T MMP-low%, Th MMP-low%, and Tc MMP-low%, but the differences were not statistically significant (all P > 0.05). Spearman correlation analysis showed that among the mitochondrial damage indicators, only the Th MMP-low%/Tc MMP-low% ratio was correlated with the immune function (Th/Tc ratio) of the AID patients (r=-0.39, P=0.001). The receiver operating characteristic curve showed that Tc MMP-low%, Tc MMP-low%, and Th MMP-low% all had good performance in identifying AID, with respective areas under the curve of 0.83(95% CI: 0.74-0.92), 0.82(95% CI: 0.73-0.92), and 0.77(95% CI: 0.67-0.88), respectively.  Conclusions  Peripheral blood T lymphocytes in AID patients have varying degrees of mitochondrial damage, especially in immunodeficient individuals. Mitochondrial damage-related indicators of T lymphocytes may serve as molecular markers for auxiliary diagnosis of AID.
In Vitro Activity of Sixteen Drugs Against Staphylococcus Aureus, Enterococcus Faecalis and Enterococcus Faecium: A Multicentre Cross-sectional Study in China
WU Yun, CHEN Jiawei, WANG Tong, LI Jin, ZHANG Ge, KANG Wei, ZHANG Jingjia, SUN Hongli, XU Yingchun, LIU Yali
2023, 14(5): 999-1004. doi: 10.12290/xhyxzz.2023-0070
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  Objective  To evaluate the in vitro antimicrobial activities of 16 common agents against Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis to provide data for the rational clinical use of drugs.  Methods  From 1st January to 31st December in 2019, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis were collected from 24 hospitals in 18 provinces in China. Antimicrobial susceptibility testing was conducted by automated instrumentation method, and WHONET 5.6 software was used to calculate the drug sensitivity results of the strains to 16 antibacterial drugs including vancomycin, norvancomycin, fusidic acid and linezolid.  Results  A total of 255 strains of Staphylococcus aureus, 117 strains of Enterococcus faecalis and 114 strains of Enterococcus faecium were collected. Blood was the most common specimen type (22.2%, 108/486), followed by urine (18.9%, 82/486). According to the drug sensitivity results, vancomycin, norvancomycin, linezolid and teicoplanin maintained high activity to all strains. All Staphylococcus aureus and Enterococcus faecalis were sensitive to vancomycin and teicoplanin, while the resistance rates of vancomycin and teicoplanin against Enterococcus faecium were 4.4% and 2.6%, respectively. The resistance rates of linezolid against Staphylococcus aureus, Eenterococcus faecium and Eenterococcus fascalis were 0, 0 and 4.3%, respectively. Norvancomycin and vancomycin showed similar antibacterial activity against Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis, with 50% minimum inhibitory concentration (MIC50) of 1 mg/L, and MIC90 of 2 mg/L. The isolation rate of methicillin-resistant Staphylococcus aureas(MRSA) was 35.7%, with 13.2% resistance to fusidic acid and 3.0% in methicillin-susceptible Staphylococcus aureas.  Conclusions  The activity of the 16 antimicro-bial drugs against Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis varied considerably. The data will provide reference for the rational use of antimicrobial drugs.
Analysis of the Clinical Value of Metagenomic Next-generation Sequencing in Central Nervous System Infection
LU Minya, GUO Jiayu, ZHANG Dong, SU Huiting, GAO Yi, ZHAO Ying, YANG Qiweng, XU Yingchun
2023, 14(5): 1005-1010. doi: 10.12290/xhyxzz.2023-0293
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  Objective  To evaluate the clinical value of metagenomic next-generation sequencing (mNGS) technology in the central nervous system (CNS) infection.  Methods  Utilizing the Infectious Disease Metagenomic Testing Platform at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, we conducted a retrospective analysis of clinical data, routine laboratory test results, and mNGS results of patients diagnosed with infectious CNS diseases from April to December 2022. The aim was to assess the diagnostic significance of mNGS technology in CNS infection.  Results  Among 39 patients clinically with CNS infection, suspected pathogenic microorganism-specific sequences were detected in 29 cases (74.4%). Among them, 11 cases (37.9%) were positive for bacteria, 13 cases (44.8%) for viruses, 3 cases (10.3%) for fungi, 1 case (3.5%) for both bacteria and viruses, and 1 case (3.5%) for both fungi and viruses, yielding a positivity rate of 74.4%. Ten cases reported negative results, resulting in a false-negative rate of 25.6%. The positivity rate of mNGS was significantly higher than that of conventional clinical pathogen detection methods (including cerebrospinal fluid smears, cultures, pathogen antigens, and nucleic acid polymerase chain reactions), with rates of 74.4% compared to 23.7%, respectively.  Conclusions  Compared to available conventional clinical pathogen detection methods, mNGS technology demonstrates a higher positivity rate in the diagnosis of infectious CNS diseases. This advancement could potentially contribute to the early diagnosis of CNS infection.
Clinical Evaluation of a Fluorescence Immunochromatographic Assay for Interleukin-6 Detection
NING Yating, MAO Leili, LI Wei, XU Jiajun, XU Yingchun, ZHANG Li
2023, 14(5): 1011-1016. doi: 10.12290/xhyxzz.2023-0186
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  Objective  To evaluate the performance of a new fluorescence immunochromatographic assay for interleukin-6 (IL-6) detection.  Methods  A total of 104 serum samples from patients with suspected infections and normal population were collected at Peking Union Medical College Hospital in December, 2021. Assay A (Wanfu biofluorescence immunochromatography assay) and B (Siemens chemiluminescence assay) were used as references to evaluate the equivalence of the Innova assay for detecting serum IL-6. Meanwhile, 39 homologous paired plasma and serum were collected to evaluate the consistency of the Innova assay in detecting IL-6 content in different types of samples.  Results  In quantitative analysis, two samples were excluded because the content was above the limit of detection for method B. Compared with the assay A or B, the regression equations of the Innova assay were Y=-7.0950+1.1924X (R2=0.9448), Y=-2.6143+1.3072X (R2=0.9391), and the Pearson correlation coefficients were 0.9720 and 0.9691, respectively. With assay A or B as reference, the Innova assay showed the Bland-Altman bias values of -3.0 and 8.0, while the expected bias at the medical decision level (7 ng/L) was -1.44 ng/L (95% CI: -5.37 to 2.50), 1.97 ng/L (95% CI: -2.09 to 6.01), respectively, with 95% CI intervals all included permissible errors (±15%, -1.05 to 1.05 ng/L). The qualitative results showed the high total coincidence rate between the Innova assay and assay A (84.6%), and assay B (83.7%). In addition, the consistency of the Innova assay was good for 39 homologous pairs of plasma and serum samples (P < 0.0001). Only one data (2.6%, 1/39) was identified by Bland-Altman bias analysis to be outside the maximum allowable error range.  Conclusions  Compared with the two reference assays with the same or different principles used in clinical practice, the Innova assay for IL-6 detection has good consistency and correlation, and its test results are almost not affected by the type of serum/plasma samples. To a certain extent, the Innova assay meets the needs of rapid detection in clinical practice.
Clinical Resistance of Helicobacter pylori and Its Trend: A 10-year Data Analysis at Peking University People's Hospital
ZHANG Feifei, WANG Qi, LI Shuguang, WANG Zhanwei, LIANG Xinyue, MENG Han, YANG Shuo, WANG Hui
2023, 14(5): 1017-1022. doi: 10.12290/xhyxzz.2023-0063
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  Objective  To study the resistance of Helicobacter pylori(Hp) isolated from Peking University People's Hospital to commonly used antibiotics, in order to provide basis for clinical rational drug use.  Methods  The drug susceptibility test data of Hp strains isolated from gastric mucosal biopsy specimens of outpatients in the Department of Gastroenterology, Peking University People's Hospital from May 2011 to December 2021 were retrospectively collected. The drug resistance rate and dual/multiple drug resistance of Hp to amoxicillin, metronidazole, clarithromycin, levofloxacin and tetracycline were statistically analyzed.  Results  A total of 120 Hp strains isolated from 402 gastric mucosa specimens (120 patients) and cultured positive were included, with a culture positive rate of 29.85%. The resistance rates of Hp to metronidazole (75.0%) and clarithromycin (72.5%) were relatively high, while the resistance rates to levofloxacin (45.8%), amoxicillin (12.5%) and tetracycline (4.2%) were relatively low. The drug resistance of Hp to clarithromycin and amoxicillin was not significantly affected by the age of the patients. The drug resistance rate to metronidazole and levofloxacin increased with the age of the patients, and the drug resistance rate to tetracycline decreased with the age of the patients. The resistance rate of female patients to levofloxacin was higher than that of male patients (56.7% vs. 32.1%, P=0.007). Over time, the resistance rate of Hp to clarithromycin increased gradually, the resistance rate to levofloxacin increased first and then decreased, the resistance rate to metronidazole fluctuated and was high overall, and the resistance rate to amoxicillin and tetracycline was not significantly affected by time and was relatively low overall. No Hp strains resistant to all five kinds of antibiotics were found. Dual drug resistance rate was 25.0%, with the simultaneous resistance of metronidazole and clarithromycin being the most common (20.0%); multiple drug resistance rate was 44.2%, with the simultaneous resistance of metronidazole + clarithromycin + levofloxacin being the most common (32.5%).  Conclusions  The resistance rate of Hp strains isolated from Peking University People's Hospital to metronidazole, clarithromycin and levofloxacin is high, and multiple drug resistance is serious. When carrying out empirical Hp root therapy in clinic, the drug regimen should be reasonably selected, and drug sensitivity test should be conducted when necessary, so as to guide the formulation of treatment regimen.
Prediction Model for In-hospital Death of Patients with Cardiac Arrest
ZHANG Nan, LIN Qingting, ZHU Huadong
2023, 14(5): 1023-1030. doi: 10.12290/xhyxzz.2023-0378
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  Objective  To build a prediction model of the in-hospital death of patients with cardiac arrest.  Methods  This study is a retrospective analysis based on the medical information mart for intensive care-Ⅳ (MIMIC-Ⅳ)2.0. We gathered the information of patients above 18 years old, with cardiac arrest and intensive care unit (ICU) experience. A stepwise multi-variate logistic regression analysis was performed to filter variables, variables with P values < 0.05 were kept and enter as predictors of in-hospital death of patients with cardiac arrest. The model was evaluated with receiver operating characteristic (ROC) curve for discriminative power and with calibration curve for consistency. Finally, an online dynamic nomogram calculator was built to calculate the risk of in-hospital death.  Results  This study included 1772 patients with cardiac arrest. The mean age of those patients was (64.93±16.52) years old, and 963 (54.3%) patients suffered in-hospital death. The factors of the prediction model for in-hospital death of cardiac arrest patients constructed based on multi-variate logistic regression included: potential cardiac disease diagnosis, age adjusted Chalson comorbidity index(CCI), body mass index (BMI), vital signs, lowest lactic acid and lowest Glasgow coma scale (GCS) during the first 24 hours after entering ICU, cardiac ultrasound examination, invasive mechanical ventilation and vasopressin utilization. The sensitivity and specificity of the prediction model were 73.1%(95% CI: 0.702-0.759) and 71.6%(95% CI: 0.683-0.745), respectively. Area under the ROC curve was 0.806(95% CI: 0.786-0.826).  Conclusions  The prediction model built in this study can properly predict the in-hospital death of patients with cardiac arrest.
Comparison of Clinical Efficacy of Different Acupuncture Therapies for Grade C Delayed Gastric Emptying after Pancreaticoduodenectomy: A Retrospective Cohort Study Based on Propensity Score Matching
LI Tianyu, ZHANG Yamin, MI Qindong, LI Zeru, BAO Fei, WANG Weibin
2023, 14(5): 1031-1037. doi: 10.12290/xhyxzz.2023-0088
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  Objective  To investigate the effect of different acupuncture methods on gastric juice drainage in patients with grade C delayed gastric emptying (DGE) after pancreaticoduodenectomy.  Methods  This was a retrospective cohort study of patients with grade C DGE after pancreaticoduodenectomy who received acupuncture treatment from January 2015 to September 2021. According to the acupuncture methods, the patients were divided into body acupuncture group and ear-body acupuncture group. The patients in both groups were matched 1∶1, using propensity score matching based on the baseline gastric fluid drainage. The differences in the primary outcome indicators[short-term (within 3 d) outcome, long-term (within 10 d) outcome] and secondary outcome indicators (length of postoperative hospital stay, proportion of patients discharged with a gastric tube, incidence of adverse events during treatment) were compared between the two groups.  Results  A total of 65 patients with DGE who met the inclusion and exclusion criteria were enrolled, including 34 patients (52.3%) in the ear-body acupuncture group and 31 patients (47.7%) in the body acupuncture group. (1)Short-term efficacy: A total of 23 patients in the ear-body acupuncture group and 23 patients in the body acupuncture group were enrolled after matching by propensity score method. The short-term decrease rate of gastric fluid drainage in the ear-body acupuncture group was higher than that in the body acupuncture group[42.7%(19.6%, 65.1%) vs. 6.5%(-14.7%, 50.6%), P=0.034]. (2) Long-term efficacy and secondary outcome indicators: There were 4 and 6 patients in the body acupuncture group and the ear-body acupuncture group, respectively, who had their gastric tubes successfully removed within 3 d of treatment. Their long-term efficacy of treatment could not be calculated, so they were excluded. After matching the two groups again using the propensity score method, a total of 16 patients in the ear-body acupuncture group and 16 patients in the body acupuncture group were included. There were no adverse events during treatment in both groups, and the rate of long-term gastric drainage decline was higher in the ear-body acupuncture group [49.6% (15.7%, 56.9%) vs. 8.8%(-9.3%, 33.1%), P=0.024] than the body acupuncture group, the postoperative hospital stay[30.0(26.0, 38.5) d vs. 31.0(24.3, 43.8) d, P=0.748] and the proportion of patients discharged with a gastric tube (18.8% vs. 25.0%, P > 0.999) were not significantly different between the two groups.  Conclusion  Compared with body acupuncture alone, auricular acupuncture combined with body acupuncture therapy is more effective in reducing gastric drainage in patients with grade C DGE after pancreaticoduodenectomy, which may be beneficial to patients' postoperative recovery.
Clinical Characteristics and Inflammatory Markers of Omicron BA.5.2 Variant Infection in Hospitalized Patients and Their Predictive Role in Disease Prognosis
LIU Huan, HUANG Xiaoling, DAI Mengying, GUO Jiejie, GAO feng
2023, 14(5): 1038-1045. doi: 10.12290/xhyxzz.2023-0055
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Abstract:
  Objective  To analyze the clinical characteristics and inflammatory indicators of hospitalized patients infected with Omicron BA.5.2 variant, and screen for possible prognostic diagnostic markers.  Methods  We retrospectively collected clinical data from hospitalized patients with Omicron BA.5.2 variant infection admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from August 1 to November 30, 2022. The patients were divided into mild, common, severe, and critically ill patient groups based on the severity of the disease. The differences in clinical data between the four groups were compared, and binary logistic regression was used to analyze inflammation indicators related to the severity of the disease. Multiple logistic regression method and receiver operator characteristic (ROC) curve were used to analyze the correlation between various indicators and patient prognosis, as well as the evaluation value for disease severity and prognosis.  Results  A total of 3006 patients who met the inclusion and exclusion criteria were included, including 1522 males (50.63%) and 1484 females (49.37%), with an average age of (58.72±18.01)(14-96) years. According to the severity of the disease, they were classified into mild (40.98%, 1232/3006), ordinary (52.56%, 1580/3006), severe (4.26%, 128/3006), and critically severe (2.20%, 66/3006) groups.There were a significant differences(all P < 0.01) in the merging of underlying diseases including cardiac disease, diabetes, hypertension, kidney disease, lung disease, malignant tumor, brain disease, viral hepatitis and autoimmune disease among each group. During the hospitalization period, a total of 74 cases (2.43%) died, including 46 cases of severe illness (63.01%), 19 cases of severe illness (26.03%), 7 cases of ordinary illness (9.60%), and 2 cases of mild illness (2.74%). The proportion of death patients aged≥70 years old was 75.68%(56/74), and all deaths were among those with underlying diseases. C-reactive protein(CRP) and albumin levels were independent risk factors for disease severity, and CRP was significantly positively correlated with disease severity(P=0.002), while albumin levels were significantly negatively correlated with disease severity (P < 0.001). CRP, systemic inflammatory response index (SIRI), and systemic immune inflammation index (SII) were independent risk factors for disease prognosis, and CRP(P=0.027) and SIRI(P=0.025) were significantly positively correlated with disease prognosis, while SII was significantly negatively correlated with disease prognosis (P=0.021). CRP, interleukin-6 (IL-6), D-dimer, and neutrophil to lymphocyte ratio (NLR) had high diagnostic value for disease severity classification with the corresponding area under the aurve(AUC) > 7.0, while CRP, IL-6, procalcitonin (PCT), D-dimer, troponin T(TnT), troponin Ⅰ(TnⅠ), NLR, SII, platelet to lymphocyte ratio (PLR), the monocyte to lymphocyte ratio (MLR) had a high prognostic diagnostic value for death or survival with the corresponding AUC > 0.70.  Conclusions  There were significant differences in clinical characteristics among hospitalized patients infected with Omicron BA.5.2 variant strains with different disease severity. Combining CRP, IL-6, D-dimer, PCT, D-dimer, TnT, TnⅠ, NLR, SII, PLR, and MLR prediction models may enable early identification of high-risk populations among hospitalized patients infected with Omicron BA.5.2 variant strains, and provide timely diagnosis and treatment.
Reviews
Recent Advances of Digital Therapeutics in Treatment of Chronic Pain
JI Heyu, CUI Xulei, HUANG Yuguang
2023, 14(5): 1046-1052. doi: 10.12290/xhyxzz.2023-0086
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Chronic pain is characterized by a high incidence and persistent, challenging recovery. It not only significantly troubles patients but also poses substantial challenges for clinical treatment. Digital therapeutics (DTx), an emerging evidence-based therapeutic approach by software programs, provides individualized disease management strategies for patients through digital networks. DTx enhances treatment adherence and facilitates data collection, which can be used as a monotherapy or in combination with other therapies. This review aims to summarize the progress of DTx application in the diagnosis and treatment of chronic pain, with the goal of providing valuable insights for the clinical management of chronic pain.
Advances in Laboratory Diagnosis of Bacterial Vaginosis
WANG Zhe, ZHAO Ying, XU Yingchun
2023, 14(5): 1053-1059. doi: 10.12290/xhyxzz.2022-0677
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Bacterial vaginosis (BV), an imbalance of normal vaginal microecology, is manifested as a mixed infection. It is characterized by a decrease of normal hydrogen peroxide-producing lactobacillus and an overgrowth of anaerobic bacteria (mobiluncus, prevotella) and facultative bacteria (gardnerella vaginalis, atopo vaginalis). BV is a risk factor for pelvic inflammatory disease, infertility, sexually transmitted pathogens (human papillomavirus, human immunodeficiency virus, neisseria gonorrhoeae, chlamydia trachomatis, etc.) infection. In addition, BV during pregnancy can lead to adverse obstetrical outcomes, including early miscarriage, premature delivery, postpartum endometritis, and low birth weight. The pathogens causing BV are diverse and have a high recurrence rate after treatment. About 10% to 50% of BV patients have no clinical symptoms and are easy to miss diagnosis. Rapid and accurate laboratory detection can provide timely diagnosis and treatment for BV patients and avoid adverse outcomes. Therefore, this paper reviews the research progress of diagnostic criteria, vaginal microecological evaluation and novel detection methods for BV, in order to provide reference for clinical diagnosis and treatment of BV.
Advances in Balloon Pulmonary Angioplasty for the Treatment of Chronic Thromboembolic Pulmonary Hypertension
GAO Luyang, LUO Qin, ZHAO Zhihui, ZHAO Qing, LIU Zhihong
2023, 14(5): 1060-1066. doi: 10.12290/xhyxzz.2023-0031
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Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic life-threatening disease caused by organized blood clots that narrow or block the pulmonary arteries, leading to redistributions of blood flow and remodeling of the pulmonary microvascular bed. This progressive increase in pulmonary vascular resistance and pulmonary arterial pressure eventually results in right heart failure or even death. Pulmonary endarterectomy (PEA) is considered the preferred treatment for CTEPH. However, approximately 40% of patients are unable to undergo PEA surgery due to distal lesions or complications. Balloon pulmonary angioplasty (BPA) is an angiographically guided catheter intervention that uses appropriately sized balloons to dilate and open narrowed or occluded pulmonary vessels step by step. BPA holds great promise for offering a new treatment option for these patients. This article reviews the clinical efficacy and predictability of postoperative complications of BPA in treating CTEPH, as well as the advances in combined treatment of BPA with PEA or with riociguat, with the aim to provide reference for clinicians in selecting treatment options for CTEPH patients.
Research Progress of Perioperative Intestinal Function Protection Strategies
HAO Ke, CHENG Baoli
2023, 14(5): 1067-1071. doi: 10.12290/xhyxzz.2023-0113
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Perioperative intestinal function injury, a common complication during postoperative recovery, is associated with preoperative abstinence from food and drink, inflammation and stress, anaesthesia, medication, and prolonged bed rest. It not only affects the digestion, absorption and excretion functions of patients, slows down the postoperative recovery process, leads to a decrease in patient satisfaction and increases the burden of medical care, but also leads to multiple organ insufficiency or even failure in severe cases. Therefore, the prevention and treatment of perioperative intestinal function injury are of great significance in shortening the hospitalisation time and accelerating the postoperative recovery of patients. In this article, we review the factors of perioperative intestinal function injury and the strategies of intestinal function protection, in order to provide a reference for the development of a reasonable intestinal function protection programme in the perioperative period.
Complicated and Rare Disease
A Case Report of Preterm Infant with Kagami-Ogata Syndrome
QUAN Meiying, SUN Zhixing, JIANG Jingjing, JIANG Yulin, LI Zhenghong
2023, 14(5): 1072-1075. doi: 10.12290/xhyxzz.2023-0073
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This paper reports a case of Kagami-Ogata syndrome in a preterm infant with gestational age of 30 weeks. Prenatal ultrasonography suggested excess amniotic fluid, large biparietal diameter and abdominal circumference, and widening of the lateral ventricles, renal pelvis, and intestinal tubes in several places. Postnatal examination showed a small jaw, collapsed nose, and upturned nostrils; the chest was narrow and bell-shaped, and the abdominal wall showed diastasis recti and a bowel pattern. Chest radiographs showed "hanger sign" ribs. Ultrasound showed widening of the lateral ventricles, hydronephrosis in both kidneys and cryptorchidism. Thyroid function tests suggested congenital hypothyroidism. Prenatal amniocentesis results obtained on day 6 after birth revealed the presence of a microdeletion of approximately 268.2 kb in the known genomic imprinted region 14q32.2 from the mother. The diagnosis of Kagami-Ogata syndrome was confirmed on the basis of the prenatal amniocentesis results and the clinical presentation of the infant after birth. The family gave up treatment after the infant was treated with ventilator, nutritional support, and antibiotics without significant improvement. In this paper, we summarize the diagnosis and treatment of this infant and review the literature inorder to enrich the clinical knowledge of this disease.
Clinical Research and Evidence Based Medicine
Public's Knowledge and Experiences Towards Pediatric Clinical Trials: Methodological Characteristics Analysis
REN Yiming, LI Rui, TANG Si, JI Guanghe, QIN Zelin, ZHAO Leying, TONG Jiaxi, CHEN Yuxuan, GAO Jiaqi, YU Mingkun, RONG Hongguo, XIA Ruyu, FEI Yutong
2023, 14(5): 1076-1083. doi: 10.12290/xhyxzz.2022-0620
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  Objective  This study aims to analyze the methodological characteristics of qualitative interview studies investigating the public's knowledge and experiences regarding pediatric clinical trials and to provide reference for the design and implementation of similar research in China.  Methods  We conducted a comprehensive search in CNKI, WanFang Data, Vip Network, PubMed, Embase, APA PsycInfo, CINAHL, and Web of Science databases. We identified all published qualitative interview studies that explored the public's knowledge and experiences related to children's participation in clinical trials up to September 21, 2021. Eight researchers were divided into four groups, with two trained researchers in each group utilizing Note Express(v 3.2) software for pre-screening and data extraction. Literature screening, data extraction, and analysis were performed independently after consistency checks. Disagreements were resolved through team leader decisions after group discussion. The CASP Qualitative Checklist Tool was used to assess study quality, and the extracted data was summarized to develop a classification framework.  Results  A total of 144 English literature (137 studies) were included. The majority of the studies (80.3%, 110/137) exhibited minimal or no quality concerns. Most studies (54.7%, 75/137) were published from 2015 to 2021. Relevant studies were published in 23 countries, with the United States (37.2%, 51/137) and the United Kingdom (26.3%, 36/137) contributing the most. There were 75.9%(104/137) of studies focusing on actual pediatric clinical trials. The main diseases covered were infectious diseases (28.9%, 35/121) and cancer (22.3%, 27/121). Interventions in clinical trials predominantly involved drug therapy (38.6%, 39/101) and vaccines (14.9%, 15/101). Interviews were conducted by medical staff in hospitals or clinics, with participants mainly recruited from clinical trial subjects (43.0%, 49/114). Most interviewees were parents (79.6%, 109/137). Compensation was often provided in the form of vouchers (46.7%, 21/45). The content of included studies largely centered on parents' perspectives and perceptions of pediatric clinical trial knowledge and processes (27.5%, 78/284). Interviews were mainly performed as semi-structured interviews (75.2%, 103/137) and face-to-face interviews (88.3%, 121/137). Thematic analysis (47.2%, 51/108) and NVivo software (77.6%, 52/67) were commonly used for data analysis. Independent multi-person analysis (46.4%, 52/112) and content verification (77.8%, 21/27) were employed to ensure reliability and credibility.  Conclusions  Semi-structured in-depth interviews with parents and children using thematic analysis are a prominent research approach. Qualitative interview studies emphasize the clinical characteristics of diseases, including disease types and interventions. Specific attention should be given to perspectives and experiences of children and parents with poor adherence or clinical outcomes. Analyzing potential participants' knowledge, attitudes, and experiences can provide references for improving future trial design and quality.
Application of Delphi Method in the Development and Revision of Clinical Practice Guidelines of Traditional Chinese Medicine: Process and Suggestions
LIANG Changhao, YIN Guanxiang, WANG Yaqi, LIU Siqi, GAO Yicheng, LIU Pengwei, SU Xiangfei, FEI Yutong
2023, 14(5): 1084-1090. doi: 10.12290/xhyxzz.2022-0649
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In the process of developing clinical practice guidelines, consensus method is essential to determine clinical problems and recommendations, among which Delphi method and modified Delphi method are the most common. Therefore, scientific and standardized application of Delphi method to reach a consensus (such as expert selection, process design) has become an important topic in urgent need of study. In the process of using Delphi method, it is necessary to refer to mature methodological suggestions to make theconsensus process structured and transparent. This article focuses on the key elements of Delphi method in the development of clinical practice guidelines, and elaborates its basic methods and processes, including the number, composition, standards and selection methods of the "expert group", as well as the key points of patients' participation. In terms of technical points, anonymity, consensus threshold and time control are described. Furthermore, the limitations of Delphi method and the highlights of the report are presented, in order to promote the standardized application of Delphi method in the development of the guidelines.
Clinical Practice Guidelines
Methods for Developing Patient and Public Versions of Guidelines: Progress and Case Studies
LIU Hui, YAO Yuanyuan, LUO Xufei, LEI Ruobing, YANG Nan, ZHAO Junxian, ZHANG Hairong, XUN Yangqin, LIU Xingrong, CHEN Yaolong
2023, 14(5): 1091-1095. doi: 10.12290/xhyxzz.2023-0356
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Patient and public versions of guidelines (PVG) have attracted increasing attention in China, and their number is also on the rise. This article explores the methods for the development of PVG, introduces and compares different development methods, and incorporates case studies for interpretation, with the aim of providing reference for the developers of PVG and further promoting the development of PVG in China.
Clinical Case Analysis
Recurrent Rhabdomyolysis and Renal Insufficiency in a Patient with Hemochromatosis
ZHOU Menglan, ZHANG Lei, YE Wenling, GAO Ruitong
2023, 14(5): 1096-1100. doi: 10.12290/xhyxzz.2023-0107
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Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, an autosomal recessive inherited disease, can be classified into three types. Type 3 VLCAD deficiency, also named as delayed intermittent myopathy, is the most common type, which can be manifested as recurrent rhabdomyolysis induced by exercise, infection or hunger. We reported the first case of recurrent rhabdomyolysis since childhood, with renal insufficiency and a history of hemochromatosis. Whole exon sequencing revealed a compound heterozygous mutation of ACADVL gene, consistent with the diagnosis of type 3 VLCAD deficiency. Further, we performed a renal biopsy to clarify the causes of the patient's renal insufficiency, which showed a tubulointerstitial injury with no lipid or iron deposition. Through reviewing the diagnosis and treatment process of this case and literature review, we hope to provide insights for the differential diagnosis of common clinical renal insufficiency induced by rare causes.
Case Report
Locally Advanced Cervical Cancer Treated with Online Adaptive Radiotherapy: A Case Report
WANG Guangyu, YAN Junfang, WANG Zhiqun, ZHANG Yu, SUN Xiansong, LI Jing, LI Wenbo, YANG Bo, ZHANG Fuquan
2023, 14(5): 1101-1105. doi: 10.12290/xhyxzz.2023-0076
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Online adaptive radiotherapy(OART)is considered to be a revolutionary technology after intensity-modulated radiotherapy. The first Chinese OART platform based on iterative cone beam computed tomography (iCBCT)has been applied in clinical treatment in Peking Union Medical College Hospital. This article reports the workflow and efficacy of first case with cervical cancer who received radical OART. After treatment, the patient achieved clinical complete remission with only a grade 1 radiation toxicity in the lower gastrointestinal tract. This article analyzes and discusses the clinical treatment process and follow-up data of this patient, aiming to provide clinical evidence for the subsequent large-scale application of artificial intelligence-driven iCBCT-guided OART technology.
Teaching and Research
Exploration and Application of Microsurgical Training in Young Neurosurgeons at Peking Union Medical College Hospital
GUO Xiaopeng, ZHANG Xiao, XING Hao, WANG Shishuai, YAO Yong, WEI junji, MA Wenbin, WANG Yu, GAO Jun
2023, 14(5): 1106-1110. doi: 10.12290/xhyxzz.2022-0529
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Microsurgical technique is essential for neurosurgeons, which demands good hand-eye coordination and fine motor skills. It is therefore necessary to provide systematic microsurgical training for young doctors with limited clinical experience. However, there is currently a lack of unified training programs in China. Based on clinical needs, the Neurosurgery Department of Peking Union Medical College Hospital has developed an integrated, immersive, and high-intensity microsurgical training course that covers training closely related to clinical practice, such as the use of microsurgical instruments, suture of gauze holes, anastomosis of artificial blood vessels, anastomosis of middle cerebral artery, and the use of micro drills. Since March 2022, six training sessions have been completed with a total of 12 trainees, and all have passed the assessment. Four of them have been recognized as microsurgical main surgeons. Preliminary data shows that this training course has helped to improve the microsurgical skills of young neurosurgeons, providing a reference for future microsurgical training programs.
Integrating Education of School History into Teaching of Clinical Courses and Developing Professional Courses with PUMC Characteristics: Taking Diabetes Teaching in Internal Medicine as an Example
LI Wei, XU Lingling, HU Yingli, ZHU Huijuan, LI Yuxiu, XIA Weibo
2023, 14(5): 1111-1115. doi: 10.12290/xhyxzz.2023-0148
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  Objective  To explore how to integrate the history of Peking Union Medical College (PUMC) into the teaching of diabetes in internal medicine, in order to develop an ideological and political theory-based course with PUMC characteristics.  Methods  The students in "4+4" medical doctor program of PUMC were enrolled into this study. Diabetes mellitus course combined with ideological and political theories course (including the history of insulin development, the life and contribution of Prof. WU Xian and Prof. LIN Kesheng, and the contributions of Prof. CHI Zhisheng, Prof. PAN Xiaoren and Prof. XIANG Hongding to the prevention and treatment of diabetes) was used for the teaching. Feedback (including the level of the political teaching knowledge before and after the course, the effectiveness of the political teaching by students after the course) was collected by questionnaire online, and statistical analysis was conducted.  Results  A total of 62 students (32 in grade 2020 and 30 in grade 2021) were included in the "4+4" pilot class of clinical medicine at PUMC. A total of 58 questionnaires were collected (30 in grade 2020 and 28 in grade 2021), with a rate of 93.5%(58/62). Before teaching, 55.2%~100% of the students had no knowledge of the course, and after teaching, all students had a general understanding, with the level of understanding significantly better than before (P < 0.001). According to the survey, 82.8% of the students thought that the course increased their interest in learning, 86.2% of the students were satisfied with the overall effect of the course, 89.7% thought that it allowed them to better understand the history of PUMC, 77.6% thought it deepened their understanding of the spirit of medical science, 82.8% thought it increased their understanding of the spirit of professional service to the country and patriotism, and 72.4% thought it increased their sense of social responsibility.  Conclusions  Integrating the history of PUMC into clinical medicine education is the unique advantage of PUMC medical education. It is conducive to students understanding of ideological and political theories, inculcation of correct values, method ology and humanistic qualities, and cultivation of the truth-seeking and pragmatic spirit of medical science.
Medical Ethics
Ethical Arguments for Withdrawing Life-sustaining Medical Intervention
ZHANG Di, NING Xiaohong
2023, 14(5): 1116-1122. doi: 10.12290/xhyxzz.2022-0332
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Decision to withdraw life-sustaining medical intervention(LSMI) is a common ethical issue in clinical practice. This paper reviews and analyzes the ethical arguments for withdrawing LSMI from three aspects: respect for autonomy, medical futility and patients' best interests. The authors argue that withdrawal of LSMI can be ethically justified when any of the following conditions is met: when patient gives valid consent, LSMI is judged to be medically futile, or it is in the patients' best interests. This paper proposes practical suggestions for the withdrawal of LSMI in clinical practice, and presents several policy suggestions. Finally, the authors identify several challenges of withdrawing LSMI in practice and possible approaches to addressing them.
The Story of Stethoscope
ZOU Hai
2023, 14(5): 1123-1124. doi: 10.12290/xhyxzz.2023-0368
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Abstract:
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