2019 Vol. 10, No. 3

Editorials
Abstract:
Gut microbiota, as a significant exogenous constituent in the human body, has sophisticated reciprocal interactions with the immune system. On the one hand, the symbiosis between microbiota and human hosts relies on the build-up of immune tolerance against microbes. While on the other, the exogenous microbial signals from microbiota tightly regulate the development of gut-associated lymphoid tissues and priming of immune cells. Alterations of the immune system per se might also disrupt the construction of microbiota. Furthermore, dysfunction of the crosstalk between gut microbiota and the immune system could possibly contribute to both local and systemic diseases, including inflammatory diseases, autoimmune diseases, and cancers. Clinical studies have shed light on the therapeutic strategies exploiting microbiota, such as supplementation of probiotics and fecal microbiota transplantation in combination with conventional immunotherapy, which achieved improved outcomes in certain diseases. Hence, a thorough and comprehensive understanding of the immunological function of gut microbiota is becoming increasingly substantial and critical.
Abstract:
Infection with the human immunodeficiency virus (HIV) requires the presence of CD4 receptors and chemokine receptors. Two of the most principal chemokine receptors are C-C chemokine receptor 5 (CCR5) and/or the chemokine (C-X-C motif) receptor 4 (CXCR4). Homozygosity of a 32-bp deletion in the CCR5 allele provides resistance against the cellular entry of CCR5-tropic HIV strains. The successful long-term control of HIV by allogeneic haematopoietic stem cell transplantations (allo-HSCT) from a donor who was homozygous for CCR5 delta32, had been documented as a "Berlin patient" and a "London patient". They bothhad remained without viral recrudescence after transplantation and discontinuation of antiretroviral therapy. However, a wide application of allo-HSCT from donors with homozygous CCR5 delta32 mutation for HIV remission is still quite challenging so far under the condition of a low percentage of homozygous CCR5 delta32 mutation, high risk of allo-HSCT, HIV tropism shift after HSCT, and huge expense. Although the "Berlin patient" and the "London patient" take a new hope to control HIV infection, it is still too early to conclude that the "cure" of HIV infection has been achieved.
Specialist Forum
Abstract:
IgG4-related disease (IRD), a multi-organ involved autoimmune disease, has been newly defined for only about 10 years. It is characterized by elevated serum IgG4, storiform fibrosis, and massive infiltration of IgG4 positive plasma cells in involved organs. Biliary tract is one of the most commonly involved organs. IgG4-related sclerosing cholangitis (IRSC) is the clinical entity of IRD in biliary tract. It always has clinical symptoms similar to biliary-pancreatic malignancy, such as localized biliary wall thickness, dilation of the bile duct, and obstructive jaundice. IRD is sensitive to the treatment of steroids with a satisfactory prognosis and does not warrant surgical treatment. However, in recent years, we met several cases that underwent an operation due to the bile duct stricture and obstructive jaundice, yet with a final pathological report of IRSC. After reviewing these cases, we found that IRSC was seldom considered before surgery. Moreover, there were some cases of biliary malignancy with elevated serum IgG4 that were misdiagnosed to be IRSC, which led to missing the best operative time. Therefore, it is of great clinical importance to widely broadcast the knowledge of IRSC and especially to deepen the understanding of IRSC for the hepatic-biliary-pancreatic surgeons.
Abstract:
The status of mental health and behavior of patients and medical personnel is an important factor affecting the management of patient safety. There is no complete patient safety without the dimension of mental health. However, there is no specific setting about mental health and behavior issue in the management guidelines of patient safety in China and abroad. This paper put forward the viewpoint that "Systematic assessment and intervention of mental health status should be integrated into patient safety management" with reference to the researches in related fields, and suggested that Delph method should be used to carry out exploratory research.
Point/Counterpoint
Abstract:
Fecal microbiota transplantation (FMT) is reported to be a promising therapy for patients with inflammatory bowel disease(IBD). Randomized controlled trials have reported the effectiveness of FMT in the treatment of ulcerative colitis. However, many associated unknowns still remain, such as the preparation, the transplantation route, donor and recipient selection, and potential adverse events including the risk of IBD flare post-FMT. Therefore, FMT should only be administered in patients with IBD in a circumstanced setting, such as clinical trials.
Original Contributions
Abstract:
  Objective  The aim of this study was to analyze the difference of intestinal microbiota in patientswith moderately severe ulcerative colitis (UC) treated with or without glucocorticoid (GC), and explore the predictive value for the response to intravenous GC medication.  Methods  The clinical data of outpatients and inpatients with moderately severe UC treated between November 1, 2016 and June 30, 2018 in the Department of Gastroenterology, Peking Union Medical College Hospital were retrospectively collected and analyzed. Patients were divided into GC-exposed group and non GC-exposed group based on whether they were exposed to GC when the fecal sample was collected. Patients from non GC-exposed group who received a full-dose of intravenous GC treatment were divided into GC-effective group and GC-refractory group according to the response after the 3-day treatment. The intestinal microbiota from fecal samples of the UC patient was detected by 16S rRNA gene amplicon sequencing method. α diversity was estimated using the Shannon index. Metastats analysis was employed in multiple comparisons of the microbiota composition.  Results  Totally 35 moderately severe UC patients were enrolled in this study, among which 20 were non GC-exposed and the other 15 were GC-exposed. Thirteen patients from the non GC-exposed group received a full-dose of intravenous GC treatment after the collection of fecal samples, and 8 of them were GC-effective, while the other 5 were GC-refractory. Patients exposed to GC or not showed little difference in intestinal microbiota α divesity(Shannon index:non GC-exposed group 3.57±0.73, GC-exposed group 3.03±1.15, P=0.123) or microbiota composition. Compared with the GC-effective group (Shannon index 3.69±0.61), the microbiota α diversity of the GC-refractory group (Shannon index 3.15±1.01) was not significantly different (P=0.248). Based on the microbiota composition, the relative abundance of Genus lactobacillus (GC-refractory 0.0015±0.0000, GC-effective 0.0141±0.0002, P=0.010) and Genus bifidobacterium(GC-refractory 0.0178±0.0005, GC-effective 0.1716±0.0382, P=0.011) was significantly lower in the GC-refractory group while that of Genus escherichia-shigella(GC-refractory 0.4161±0.0750, GC-effective 0.1093±0.0173, P=0.008) and Genus prevotella 9 (GC-refractory 0.0176±0.0004, GC-effective 0.0018±0.0000, P=0.044) was significantly higher.  Conclusions  The α diversity or composition of intestinal microbiota of patients with moderately severe UC may not be correlated with GC treatment. It is possible that pre-treated microbiota composition is related to the response to the intravenous GC treatment.
Abstract:
  Objective  The aim of this study was to investigate the difference in the diversity of intestinalmicrobiota of psoriasis patients compared with that of healthy people.  Methods  Fresh fecal samples and clinical data of hospitalized psoriasis patients from May 2017 to June 2018 in the Institute of Dermatology of Chinese Academy of Medical Sciences & Peking Union Medical College were prospectively collected. Healthy people undergoing physical examination during the same period were selected as the healthy control. After DNA extraction of intestinal microbiota and the gene amplification of 16S rDNA, the paired-end 2×300 strategy was used to sequence by Illumina platform. According to Gold database and the similarity-clustering operational taxonomic unit (OUT) > 97%, intestinal microbiota was annotated and classified by Silva database. The species difference of samples at all levels was analyzed using Rank sum test. The main index of α diversity and the analysis of β diversity were calculated using QIIME software. All indexes were analyzed by Welch's t test and P < 0.05 was considered statistically significant. The results were shown by R and GraphPad Prism plotting.  Results  Totally 11 psoriasis patients and 21 healthy controls were eligible for this study. Between the psoriasis group and the healthy group, the ratios of gender, age, and body mass index showed no statistical significance (all P > 0.05). The DNA sequencing showed that coverage index of samples' sequencing was > 0.99. The OTU numbers (278.18±89.75 vs. 722.95±152.81, t=10.36, P < 0.01), Zhao index (433.38±147.47 vs. 1156.08±292.50, t=9.291, P < 0.01), Shannon index (3.56±0.87 vs. 5.73±0.78, t=6.972, P < 0.01), and Simpson index (0.79±0.15 vs. 0.94±0.04, t=3.287, P < 0.01) of the particular species of intestinal microbiota in the psoriasis group were significantly lower than those of the healthy group. The Rank-abundance curve showed that the psoriasis group had a lower evenness of intestinal microbiota. PCoA analysis (unweighted) showed that the first principal component (24.35%) was significantly separated between the two groups; however, Weighted UniFrac analysis showed that it was not clearly distinguished when the samples of the psoriasis group were mixed with the healthy group, which was independent of the subtypes of psoriasis. Through the sample clustering analysis, the intestinal microbiota partly overlapped between the two groups and the special microbiota were less in the psoriasis group. In the phylum level, TM7 could be detected in the healthy group and its relative abundance was 0.000 066 9 (0.000 033 4~0.000 200 5), while it was at micro-level in a few samples of the psoriatic group with a relative abundance of 0(Rank sum test, P < 0.05). On the genus level, the psoriasis group had significantly lower bifidobacterium[0.000 033 4(0.000 016 7~0.000 100 3) vs. 0.000 401 1 (0.000 200 5~0.001 337 0)], brauteria[0.000 467 9 (0.000 183 8~0.000 434 5) vs. 0.002 206 0(0.000 935 9~0.005 582 0)], and fecal coccus[0.000 033 4 (0~0.000 401 1) vs. 0.000 902 5(0.000 334 2~0.005 315 0)] compared to the healthy group. Dialisteria and haemophilus appearing in the healthy group were only found in a few samples in the psoriasis group. Klebsiella existed in a few samples of the two groups but was lower in the psoriasis group (relative abundance was close to 0) (Rank sum test, all P < 0.05). The high abundance analysis of individual samples showed that in some psoriasis samples, the abundance of the taxa related to the metabolism of polysaccharides and short-chain fatty acids was decreased.  Conclusion  Diversity of intestinal microbiota in psoriasis patients is lower than that of healthy people.
Abstract:
  Objective  The aim of this study was to develop a CT image-based evaluation system for systemic lupus erythematosus(SLE)associated with gastrointestinal involvement.  Methods  The clinical data of SLE patients with gastrointestinal(GI) involvement from September 2013 to May 2018 were retrospectively analyzed. The bowel wall thickness and extra-GI organs involvement were recorded by CT imaging. A new CT scoring system was established. Then the relationship between the CT score and the time to GI functional recovery, the length of hospital stay, the systemic lupus erythematosus disease activity index (SLEDAI), and laboratory findingswere analyzed.  Results  A total of 63 SLE patients with GI involvement were enrolled, including 60 females and 3 males with a mean age of (36.7±13.1)years and SLE duration of 4 (1-8) years; 54 patients (85.7%, 54/63) had GI tract thickness/edema; 31 patients (49.2%, 31/63) had extra-GI involvement; the average intestinal wall thickness was (7.8±3.7)mm. CT score was positively correlated with the time of GI functional recovery (r=0.365, P=0.003). Compared to those with a CT score >2, patients with a CT score ≤ 2 had a shorter time of GI recovery[(7.9±6.2)d vs. (15.8±13.8)d, P=0.006)], a shorter length of hospital day[(17.1±9.0)d vs. (25.7±20.5)d, P=0.043)], a lower SLEDAI(7.6±4.4 vs. 12.2±7.2, P=0.004); and were less likely to receive higher dose of corticosteroids (60.7% vs. 88.6%, P=0.010).  Conclusion  The CT scoring system can be used to assess the severity of SLE in patients with GI involvement.
Abstract:
  Objective  The aim of this study was to explore the efficacy and safety of infliximab (IFX) for severe/refractory intestinal Behcet's disease (BD).  Methods  The clinical data of intestinal BD patientstreated with IFX from September 2012 to November 2018 in Peking Union Medical College Hospital were retrospectively collected and analyzed, including clinical manifestations, endoscopic manifestations and pathology, imaging examinations, medication before and after IFX treatment, treatment response and prognosis. The clinical symptoms and endoscopic ulcer healing before and after treatment were analyzed and compared. Meanwhile, the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity index for intestinal BD (DAIBD), and the dosage of glucocorticoid before and after IFX treatment were compared by paired t-test.  Results  Twelve patients (10 males and 2 females) were enrolled, with a mean age of (29.5±10.5) years old; all were active with intestinal BD. The median time between diagnosis of BD and initiation of IFX therapy was 27.0(4.3, 109.5)months. All patients had abdominal pain and gastrointestinal ulcer, in which 8 cases with diarrhea, 11 with gastrointestinal bleeding, 4 with intestinal obstruction, and 3 with intestinal perforation were documented. After using IFX, the symptoms of all the patients were improved; the ulcers gradually healed; the gastrointestinal bleeding stopped. One patient with intestinal perforation was conducted surgery at the same time, and another with colonic stenosis after remission received ileus segmentectomy. The ESR level[4.0(2.0, 6.8)mm/h vs. 28.5(10.3, 52.3)mm/h, P < 0.01], CRP level[0.6(0.5, 1.7)mg/dl vs. 26.8(9.1, 47.1)mg/dl, P < 0.01], DAIBD(37.5±27.3 vs. 126.7±49.0, P < 0.01], and the dosage of glucocorticoid[13.8(1.9, 16.9)mg/d vs. 40.0(16.3, 56.3)mg/d, P < 0.01] were significantly decreased. Furthermore, the types of immunosuppressants being used were gradually decreased or unchanged. No serious infectious and adverse events were observed.  Conclusion  IFX, in combination with corticosteroids and immunosuppressants, is safe, effective, and well tolerated for severe/refractory intestinal BD.
Abstract:
  Objective  To analyze the effects of the receptor-IgG Fc fusion protein of recombinant type Ⅱ human tumor necrosis factor-α(TNF-α) on serum levels of adiponectin (APN), retinol binding protein 4(RBP4), and leptin (LEP) in patients with moderate to severe plaque psoriasis.  Methods  A total of 30patients with moderate to severe plaque psoriasis and 25 healthy volunteers were enrolled in the study. The psoriatic patients were subcutaneously injected with type Ⅱ human TNF-α receptor-IgG Fc fusion protein 50 mg once a week for 12 weeks. The serum levels of APN, RBP4, and LEP were assessed and compared before and after the treatment of 12 weeks, in psoriatic patients, as well as in the controls. Spearman correlation analysis was used to evaluate the linear correlations of baseline serum APN, RBP4, LEP levels with psoriasis area and severity index(PASI) in the treatment group.  Results  Before the treatment, the levels of APN[9.73(6.69, 12.37) vs. 14.25(10.53, 23.28), P < 0.001] and LEP[0.42(0.17, 2.60) vs. 3.90(1.38, 7.20), P=0.002] were lower, RBP4 was higher[12.29(10.62, 21.33) vs. 9.13(7.36, 15.78), P=0.024] in psoriatic patients than those in normal controls. After the treatment, the levels of APN[11.95(8.12, 15.26)vs. 9.73(6.69, 12.37), P=0.027] and LEP[2.84(1.04, 9.34)vs. 0.42(0.17, 2.60), P < 0.001] in the psoriatic patients were markedly increased, while the level of RBP4 showed no significant change(P=0.125). There was no linear correlation of the levels of APN, RBP4, LEP with PASI in the baseline period.  Conclusions  APN, RBP4 and LEP are closely related to the chronic inflammatory state of psoriasis. Anti-TNF-α therapy may improve the metabolic state of patients with psoriasis.
Abstract:
  Objective  The aim of this study was to summarize and analyze the in vitro antimicrobial susceptibility of Ureaplasma species and Mycoplasma hominis and the mechanisms responsible for resistance to quinolones.  Methods  The clinical data of Ureaplasma species and Mycoplasma hominis detected by in vitro culture from September 2012 to April 2017 in Peking Union Medical College Hospital were retrospectively collected and analyzed; their characteristics of antimicrobial susceptibility were also analyzed combined with the information about the patients and species identification. According to the drug-resistance characteristics of quinolone, the target genes were amplified and sequenced by PCR, and the sequencing results were translated into protein sequences. The mutations in DNA gyrase(GyrA/GyrB) and topoisomerase Ⅳ (ParC/ParE) that were related to quinolones resistance were detected by comparing sequences in the NCBI database.  Results  In vitro sensitivity to antibiotics of Ureaplasma species mixed with Mycoplasma hominis was significantly lower than that of Ureaplasma species or Mycoplasma hominis alone. Compared to Mycoplasma hominis, Ureaplasma species was less susceptible to quinolones, tetracycline, josamycin, and primycin, except for macrolides, but the difference was not statistically significant (all P > 0.05). In addition, the susceptibility of Ureaplasma species to azithromycin, erythromycin, clarithromycin, and ofloxacin in female patients was lower than that in male patients (all P < 0.05). Ureaplasma parvum were more susceptible than Ureaplasma urealyticum to most antibiotics, especially tetracycline (98.48% vs. 72.73%; 25.75% discrepancy, P < 0.05). Moreover, twenty-one mutations from sequences of GyrA, GyrB, ParC, and ParE were determined. The mutation in ParC with S83L substitution was the most frequent, 96.22% (51/53); mutations of A136T substitution in ParC, R448K substitution in ParE, and L176F in GyrA combined with S83L in ParC were also detected. This study also found six novel mutations that have not been reported:L540F, R718W, Q767E, S789N, M828I, and I831T amino acid substitutions in ParC protein.  Conclusions  The in vitro antimicrobial susceptibility of Ureaplasma species or Mycoplasma hominis is associated with genus, and the in vitro sensitivity of Ureaplasma species to antibiotics is correlated with species and genders of patients. Sole S83L substitution in ParC might be the major mechanism of resistance to quinolones of Ureaplasma species, while the possible function of the six novel mutations remains further studies.
Reviews
Abstract:
The significance of microbiota in regulating mucosal homeostasis has been addressed intensively in recent years. Meanwhile, research on human microorganism communities and their interaction with the immune system has achieved great advancement. As an essential component of the human microbiota, the gut commensal flora plays a unique role in maintaining a sophisticated balance between host defense and immune tolerance. Dysbiosis of gut microbiota may result in alterations of the innate immune system via multiple strategies. This review summarizes the underlying mechanisms of the interplay between microbiota and the innate immune system, focusing on gut-associated lymphoid tissue, innate lymphoid cells, and phagocytes.
Abstract:
The intestinal microbiota has a profound effect on human health and diseases. It affects the development of the immune system of the host and vice versa. At present, the intestinal microbiota has been found to be involved in many autoimmune diseases. Gastrointestinal tract involvement is common in patients with systemic sclerosis (SSc). Studies found that the gastric and intestinal flora of SSc patients are in disorder, and some of the specific bacteria are related to the severity of gastrointestinal involvement in SSc patients. In this paper, the related research on the intestinal flora of SSc was reviewed, such as changes in intestinal flora, the relationship between the intestinal flora and dyskinesia and fibrosis of the digestive system, and the progress of treatment.
Abstract:
The infection and treatment of Helicobacter pylori(Hp) is a hot topic of global concern. However, in recent years, Hp resistance has increased and the eradication rate has decreased in most regions of the world. Therefore, current first-line therapy to eradicate Hp has been adjusted to the quadruple therapy, using more antibiotics and longer duration than the triple therapy. It has an inevitable effect on the gastrointestinal microecology and causes an imbalance of gastrointestinal flora, changes of the composition of the gastrointestinal micro-ecological system, decrease of dominant flora, overgrowth of the intestinal bacteria, and colonization of Clostridium difficile, etc. The above changes are likely related to the adverse reactions during the eradication of Hp and the recurrence of infection thereafter.
Abstract:
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world. The main treatment is surgery intervention, especially for the early-stage of NSCLC. The pathological lymph node metastasis is closely associated with the staging and prognosis of patients. Among N2 metastasis, skip N2 metastasis is a quite common phenomenon with a better prognosis. The aim of this article is to summarize the clinical pathological features and prognosis of NSCLC with skip N2 metastasis and to guide the clinical decision making.
Abstract:
Fibrosis is the characteristic hallmark of systemic sclerosis (SSc). Although the specific mechanism has been unknown, the role of macrophages in the development of this complex disease through various ways cannot be negligible. Findings during the past 5 years have contributed to more understanding of the relationship between macrophages and SSc. This review is mainly about the progress of research on macrophages in SSc. We discuss whether or not macrophages skew toward the M1-like phenotype from the profibrotic M2-like phenotype. Some biomarkers are also listed. In addition, we elaborate on the association of macrophages with other immune cells and Tall-like receptors.
Clinical Research and Evidence Based Medicine
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In recent years, with the rapid development of information technology and the increasing demand for evidence-based healthcare practice and policy decisions, the value of real-world data has received extensive attention. One of the most important applied areas of real-world data is disease management. Its core concepts lie in the application of rigorous and pre-specified designs to data of large volume, multiple sources, and high quality. By doing so, the high-quality real-world evidence for disease burden, diagnosis, prevention, treatment, and prognosis is generated to inform the development of guidelines, clinical pathways, and technical standards for disease management, which ultimately improves healthcare quality and safety. This paper systematically discussed important issues regarding the use of real-world data for research on disease management.
Clinical Practice Guidelines
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To help clinicians, health policy makers, health administrators, and patients better know the concepts, meaning, and roles of clinical practice guidelines, Medical Journal of Peking Union Medical College Hospital plans to dedicate one special column to publish a series of papers to analysis the status quo, challenges, and opportunities of domestic and international clinical practice guidelines, and then provide recommendations and suggestions on how to improve clinical practice guidelines in China.
Breast Cancer
Abstract:
Elderly patients with breast cancer are often involved in complicated comorbidities. Besides the primary tumor, when formulating effective local therapeutic plans, clinicians should also evaluate the function of important organs and tolerance of elderly patients to the treatment. Compared with other subtypes, triple negative breast cancer(TNBC) is mainly characterized by strong invasiveness and a poor prognosis. The choice of locoregional treatment is more difficult for elderly patients with TNBC and clinically positive axillary lymph nodes. For such a special group, more reasonable individualized treatments need to be explored.
History of Medicine
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The Social Service Department of Peking Union Medical College Hospital was the first department that ever established medical social work in China. It also was the origin of the practice of medical social work in the mainland and Taiwan of China. A brief introduction of the history and working procedure of the department was given to promote a better understanding of it. The author would like to emphasize the importance of paying attention to the social-psychological causes of diseases as well.
2019, 10(3): 299-303. doi: 10.3969/j.issn.1674-9081.2019.03.020
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2019, 10(3): 309-309.
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2019, 10(3): 310-312. doi: 10.3969/j.issn.1674-9081.2019.03.022
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