莫拉菌属是需氧革兰阴性球菌,包括7种:亚特兰大莫拉菌、犬莫拉菌、卡他莫拉菌,腔隙莫拉菌、林氏莫拉菌、非液化莫拉菌和奥斯陆莫拉菌.奥斯陆莫拉菌是人类皮肤、黏膜和呼吸道正常菌群的一部分,奥斯陆莫拉菌引起的感染包括菌血症、导管相关血流感染(catheter related blood stream infection,CRBSI)、感染性心内膜炎、脑膜炎、腹膜炎、眼内炎、化脓性关节炎[～12],仅有2例由奥斯陆莫拉菌引起的单部位骨髓炎的相关报道[4,8].本文报道1例不明原因发热,最后确诊为奥斯陆莫拉菌引起的多发性骨髓炎病例.

Background Carbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease. Methods Stool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates. Results The total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF ( P = 0.018), the history of pulmonary infection within past 3 months ( P = 0.001) and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months ( P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. bla KPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered. Conclusions The present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.

患者,男,42 岁,因"皮肤巩膜黄染 30 余年加重 1 年"于2017 年8 月16 日入院. 患者 30 余年前无明显诱因出现皮肤巩膜黄染和尿色加深,不伴发热、乏力、纳差、皮肤瘙痒和大便颜色变浅,未诊治.

Klebsiella pneumoniae is an important Gram-negative opportunistic pathogen that is responsible for a variety of nosocomial and community-acquired infections. Klebsiella pneumoniae has become a major public health issue owing to the rapid global spread of extensively-drug resistant (XDR) and hypervirulent strains. Biofilm formation is an important virulence trait of K. pneumoniae. A biofilm is an aggregate of microorganisms attached to an inert or living surface by a self-produced exo-polymeric matrix that includes proteins, polysaccharides and extracellular DNA. Bacteria within the biofilm are shielded from antibiotics treatments and host immune responses, making it more difficult to eradicate K. pneumoniae-induced infection. However, the detailed mechanisms of biofilm formation in K. pneumoniae are still not clear. Here, we review the factors involved in the biofilm formation of K. pneumoniae, which might provide new clues to address this clinical challenge.

Abstract Background Follow-up study of coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. Methods A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. Results 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. Conclusions Physiological, laboratory, radiological, or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, and liver functions are common in patients who recovered from coronavirus disease 2019 (COVID-19) up to 12 months post-discharge.

Abstract. Background:. Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces. Methods:. In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality. Results:. The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively. Conclusions:. We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.

Introduction. Macrophages polarization is essential in infection control. Llipopolysaccharide (LPS) plays an essential role in host innate immune system–pathogen interaction. The LPS structure of Pseudomonas aeruginosa modifies in the adaptation of this pathogen to biofilm-related chronic infection. Gap statement. There have been several studies on LPS induced polarization of human and mouse macrophages with different results. And it was reported that the lipid A structure of the LPS derived from biofilm-forming Pseudomonas aeruginosa strain PAO1 was modified. Aim. This study aimed to investigate the effect and the involved pathway of LPS from biofilm-forming PAO1 on human and murine macrophage polarization. Methodology. LPS was isolated from biofilm-forming and planktonic PAO1 and quantified. Then the LPS was added to PMA-differentiated human macrophage THP-1 cells and Raw264.7 murine macrophage cells. The expression of iNOS, Arg-1, IL4, TNF-α, CCL3, and CCL22 was analysed in the different cell lines. The expression of TICAM-1 and MyD88 in human THP-1 macrophages was quantified by Western blot. PAO1 infected macrophages at different polarization states, and the intracellular bacterial growth in macrophages was evaluated. Results. LPS from biofilm-forming PAO1 induced more marked hyperinflammatory responses in THP-1 and Raw264.7 macrophages than LPS derived from planktonic PAO1, and these responses were related to the up-regulation of MyD88. Intracellular growth of PAO1 was significantly increased in THP-1 macrophages polarized by LPS from biofilm-forming PAO1, but decreased both in THP-1 and Raw264.7 macrophages polarized by LPS from planktonic PAO1. Conclusion. The presented in vitro study indicates that LPS derived from biofilm-forming PAO1 induces enhanced M1 polarization in human and murine macrophage cell lines than LPS from planktonic PAO1.

Carbapenems are important antibiotics for the treatment of severe infection by Gram-negative bacteria, especially for Enterobacteriaceae infection. With the widespread use of carbapenem antibiotics, carbapenem-resistant Enterobacteriaceae (CRE) has become increased year by year, which has multiple transmissible mechanism, fast spread, high mortality and undesirable clinical therapeutic effect. CRE colonization is a risk factor for CRE infection and increases mortality of critically ill patients and economic burden of society. In order to control colonization of CRE, the main strategies include performing active screening, strengthening prevention and control measures of nosocomial infections and decolonization. CRE decolonization can reduce colonization rate to some extent. It is still controversial if it can reduce the mortality of patients and the social economic burden. In this article, the epidemiology of CRE colonization, active screening, prevention and control measures of nosocomial infections and methods of decolonization are summarized.

目的 探讨肝胆胰疾病多学科团队(multi-disciplinary team,MDT)单中心开展的7年总体情况和效果,为国内同行提供参考.方法 收集华中科技大学同济医学院附属同济医院肝胆胰疾病MDT病例的基本信息.对MDT工作开展的总体情况,包括病人的地域分布、疾病归类、专家到场情况、讨论结果以及落实情况等进行统计分析.结果 成功开展188期,讨论病例数共689例次,按病种分类,肝脏原发疾病占31.2％,肝转移瘤占27.6％,胆道疾病占19.2％,胰腺疾病占16.3％,腹膜后肿瘤占5.8％;按疾病的性质分类,良性疾病占19.0％,恶性肿瘤占81.0％.专家到场参加M D T讨论的平均出场率为92.3％,首席专家及执行组长出场率为83.2％.单例讨论时间由最初的(26.4±11.7)min降至目前的(12.2±4.5)min.讨论结果的落实率为76.5％,反馈率为35.7％.结论 稳定的组织框架和长效工作机制是保证MDT高效持续开展的重点.MDT开展过程中,讨论结果的落实以及病人持续性的反馈是工作的难点.

Multidrug-resistant bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as "the last treatment option." In this study, we isolated a clinical CRKP strain named as K. pneumoniae R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS4 family ISKpn72 element into the colistin-resistance associated mgrB gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of ISKpn72 containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of ISKpn72 could be inserted into the mgrB gene to cause colistin-resistance, though the plasmid-derived ISKpn72 without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive K. pneumoniae strain transferred with the ISKpn72 element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the ISKpn72-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.

Objective: To establish and evaluate a rapid nucleic acid detection method for SARS-CoV-2 based on COYOTE® Flash20 real-time fluorescent quantitative PCR instrument. Methods: A rapid reaction system was constructed by using specific primer and probe sets targeting ORF1ab and N gene of SARS-CoV-2, and the sensitivity and specificity of the system were verified. At the same time, 108 clinical samples of COVID-19 were used to evaluate the application of this method. Results: The detection method did not require nucleic acid extraction, and the manual operation time was only one minute. After the sample was sent to the system, the test could be completed in 30 minutes. The detection limit of this method was 4×102 copies/ml. It had no cross-reactivity with other human coronaviruses (including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV and MERS-CoV) and other respiratory viruses. The evaluation of clinical sample application showed that the total coincidence rate with the conventional RT-qPCR which required nucleic acid extraction was 98.15%. Conclusions: Through the application evaluation of the rapid fluorescent quantitative PCR method of SARS-CoV-2, it was found that the method was simple, fast, specific and sensitive, and it was suitable for real-time and rapid detection needs in varieties of situations. Copyright © 2021 by the Chinese Medical Association.

时光荏苒，岁月如梭，伴随着仍然肆虐全球的重大传染病新冠肺炎疫情防控的常态化，不平凡的2020年将载入历史。本文回顾了2020年度感染（传染）病学部分领域的研究和进展，既有发病机制的新突破，也有相关临床诊疗方案的新跨越，重点关注了重大感染（传染）病新冠肺炎、病毒性肝炎/肝衰竭、病毒性肝炎合并脂肪肝、结核病、艾滋病、耐药菌感染等领域。星海拾贝，难免挂一漏万，仅供参考。

To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID-19). A total of 27 patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin-1 beta (IL-1 beta), IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF)-alpha, C-reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL-1 beta, IL-2R, IL-6, IL-8, IL-10, CRP, and serum ferritin) between male and female patients. Levels of IL-2R, IL-6, TNF-alpha, and CRP decreased significantly after treatment, followed by IL-8, IL-10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL-1 beta was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID-19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro-inflammatory response and decreased level of T lymphocytes were associated with severe COVID-19.

目的 比较不同临床分型的新型冠状病毒肺炎患者实验室检查结果与病情严重程度的相关性.方法 以2020年2月1日至2020年2月21日在华中科技大学同济医学院附属同济医院发热病房住院的50例确诊新型冠状病毒肺炎患者为研究对象,根据国家卫生健康委员会的诊断标准,该50例患者被分为危重型(8例)、重型(32例)、普通型(10例),比较不同型别患者的血常规、血生化、凝血常规结果和炎症因子的表达水平,分析上述指标的变化规律及其与临床分型的关系.结果 危重型患者白细胞和中性粒细胞计数明显高于重型和普通型患者(P<0.05);危重型和重型患者淋巴细胞计数下降较普通型患者更明显(P<0.05);危重型患者较重型和普通型患者乳酸脱氢酶水平升高,肾功能损害、凝血功能异常更明显(均P<0.05);危重型患者的降钙素原、超敏C反应蛋白、IL-6和TNF-α水平升高较重型和普通型患者更明显(均P<0.05);超敏C反应蛋白水平在重型和普通型患者之间的差异也具有统计学意义(P<0.05).结论 危重型新型冠状病毒肺炎患者更易合并细菌感染和多器官功能损害;超敏C反应蛋白、IL-6、TNF-α表达水平可灵敏反映患者全身炎症反应程度,有助于疾病临床分型.

Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression.

Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.

"感染病学"是临床医学重要课程之一,当前的临床教学存在临床教学时间短、带教老师时间少、学生学习目标不明确、兴趣缺乏等问题.本研究就建构主义理论结合网络平台引入该课程临床教学中的必要性、优势及实施方式作一探讨,以期为"感染病学"的临床教学改进提供参考.

Objectives To construct Moloney murine leukemia virus (MLV) and human immunodeficiency virus (HIV) integrase and Brd2 eukaryotic expression plasmids and label them with a fluorescent protein to study the basis for interaction between Brd2 and MLV and HIV integrases using laser confocal microscopy. Methods Prr88-MLV, HIV plasmid pNL4-3, and a Brd2-containing plasmid were used to amplify MLV-IN, HIV-IN, and Brd2 fragments with PCR.An enzyme digestion reaction system was used to construct the plasmids psectag2 A-GFP-mIN, psectag2 A-GFPhIN, and pDsred2-N1-Brd2.All plasmids were recovered using 0.8％agarose gel electrophoresis and sent out for sequencing.The recombinant plasmids were transfected into 293 Tcells, and transgene expression was tested using Western blotting.Expression of the transfected plasmid was determined by observing the corresponding fluorescence. ResultsThe HIV and MLV integrase plasmids psectag2 A-GFP-hIN and psectag2 A-GFP-mIN and the Brd2 plasmid pDsred2-N1-Brd2 were constructed.Results of sequencing and enzyme digestion matched expectations according to a comparison of NCBI blast modules and agarose gel electrophoresis.Each plasmid was transfected into 293 Tcells, and the expression of the transfected plasmid was detected by observing fluorescence with laser confocal microscopy and corresponding proteins with Western blotting. Conclusion HIV and MLV integrase plasmids have been successfully constructed and labeled with green fluorescent protein.A Brd2 plasmid was also successfully constructed and labeled with red fluorescent protein, though the Brd2 plasmid expressed rather weak fluorescence.However, this work is crucial to future research on Brd2 interaction.