目的 探讨慢性乙肝(CHB)不同免疫自然史阶段肝脂肪变性程度与血清病毒学及肝脏病理的关系.方法 选取2013年10月至2020年9月在浙江省人民医院行肝脏穿刺活检的175例CHB患者为研究对象,根据肝脂肪变性程度分为F0～F1组(无或轻度肝脂肪变性)122例和F2～F4组(中重度肝脂肪变性)53例,比较不同肝脂肪变性程度患者临床资料以及各免疫自然史阶段不同肝脂肪变性程度患者血清病毒学指标.结果 175例CHB患者肝脂肪变性发生率为46.3％.F2～F4组患者BMI、高脂血症占比、血清HBsAg水平均明显高于F0～F1组(均P＜0.05);但两组患者年龄、Hb、PT、ALT、AST、ALP、谷氨酰转肽酶、抗病毒治疗占比、HBVDNA水平、HBeAg水平以及免疫自然史比较,差异均无统计学意义(均P＞0.05).在免疫清除期,G3～G4或S0～S2时F2～F4组血清HBsAg水平均明显高于F0～F1组(均P＜0.05),G3～G4时F2～F4组血清HBeAg水平明显高于F0～F1组(P＜0.05);而G0～G2或S3～S4时不同肝脂肪变性程度患者血清病毒学指标比较,差异均无统计学意义(均P＞0.05).在免疫耐受期、免疫控制期、再活动期,各炎症及纤维化程度分期不同肝脂肪变性程度患者血清病毒学指标比较,差异均无统计学意义(均P＞0.05).结论 在CHB不同免疫自然史阶段,仅发现免疫清除期随着肝脏炎症程度的加重,中重度肝脂肪变性患者血清HBsAg、HBeAg水平明显升高;而随着肝纤维化的加重,中重度肝脂肪变性患者血清HBsAg水平明显降低.

Exosomes, one of three main types of extracellular vesicles, are ~30–100 nm in diameter and have a lipid bilayer membrane. They are widely distributed in almost all body fluids. Exosomes have the potential to regulate unknown cellular and molecular mechanisms in intercellular communication, organ homeostasis, and diseases. They are critical signal carriers that transfer nucleic acids, proteins, lipids, and other substances into recipient cells, participating in cellular signal transduction and material exchange. ncRNAs are non-protein-coding genes that account for over 90% of the genome and include microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). ncRNAs are crucial for physiological and pathological activities in the liver by participating in gene transcription, posttranscriptional epigenetic regulation, and cellular processes through interacting with DNA, RNA, or proteins. Recent evidence from both clinical and preclinical studies indicates that exosome-derived noncoding RNAs (ncRNAs) are highly involved in the progression of acute and chronic liver diseases by regulating hepatic lipid metabolism, innate immunity, viral infection, fibrosis, and cancer. Therefore, exosome-derived ncRNAs have promising potential and clinical implications for the early diagnosis, targeted therapy, and prognosis of liver diseases.

Background The chronic visceral subtype of acid sphingomyelinase deficiency, commonly known as Niemann Pick disease type B (NPDB), is a relatively rare autosomal recessive genetic disorder that is caused by mutations in the SMPD1 gene. NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS), as it lacks specific clinical characteristics. This makes its diagnosis difficult. Case presentation Here, we report a case of NPDB with SBH that was misdiagnosed as BCS for three years. A 20-year-old female with abdominal distension, hepatosplenomegaly, and haematological anomalies was initially diagnosed with BCS based on her imaging finding of a thin hepatic vein and rapid blood flow at the confluence of the hepatic vein and inferior vena cava. Her bone marrow cytology found sea-blue histiocytes. Liver biopsy showed foamy cytoplasm in hepatocytes surrounded by numerous Kupffer cells. Sequencing analysis of the SMPD1 gene led to the finding of two missense mutations in the heterozygous state: C.829 T > C (p.Trp277Arg) in exon 2 (novel) and c.1805G > A (p.Arg602His) in exon 6 (already described). These findings established the diagnosis of NPDB. Conclusion The patient presented with hepatosplenomegaly, haematological anomalies, and dyslipidaemia. Thus, NPDB should be considered following the exclusion of related diseases. The diagnosis of NPDB was suspected by clinical symptoms and routine laboratory tests and was confirmed by liver biopsy and gene sequencing. The novel mutation c.829 T > C in exon 2 of the SMPD1 gene has never been reported and needs to be further investigated.

Objectives: Here, we retrospectively described the diagnosis and treatment of 32 cases diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic. Methods: Clinical information was collected from all the patients. Reverse transcription–PCR and ELISAs were conducted for the detection of COVID-19 using nasal swabs and bronchoalveolar lavage fluid (BALF) samples. Metagenomic next-generation sequencing (mNGS) was performed for the identification of causative pathogens using BALF, peripheral blood and sputum samples. End-point PCR was performed to confirm the mNGS results. Results: All 32 patients showed atypical pneumonia and had infection-like symptoms that were similar to COVID-19. Results of reverse transcription–PCR and ELISAs ruled out COVID-19 infection. mNGS identified C. psittaci as the suspected pathogen in these patients within 48 hours, which was validated by PCR, except for three blood samples. The sequence reads that covered fragments of C. psittaci genome were detected more often in BALF than in sputum or blood samples. All patients received doxycycline-based treatment regimens and showed favorable outcomes. Conclusion: This retrospective study, with the highest number of C. psittaci pneumonia enrolled cases in China so far, suggests that human psittacosis may be underdiagnosed and misdiagnosed clinically, especially in the midst of the COVID-19 pandemic.

BACKGROUND:Liver cancer is one of the most highly malignant cancers, characterized by easy metastasis and chemoradiotherapy resistance. Emerging evidence indicates that long noncoding RNAs (LncRNAs), including Lnc524369, are highly involved in the initiation, progression, radioresistance, and chemoresistance of hepatocellular carcinoma (HCC). However, the function of Lnc524369 remains unclear.AIM:To explore the function of Lnc524369 in HCC.METHODS:To investigate the effect of Lnc524369, tissue from 41 HCC patients were analyzed using CCK8, migration, and invasion assays. Lnc524369 and YWHAZ (also named 14-3-3ζ) mRNA were detected by qPCR, and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues. The Cancer Cell Line Encyclopedia (CCLE) databases, STRING database, Human Protein Atlas database, and the TCGA database were used for bioinformatic analysis.RESULTS:Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues. Overexpression of Lnc524369 was associated with the proliferation, migration, and invasion of liver cancer cells. YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer, which could be attenuated by overexpression of Lnc524369. Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time.CONCLUSION:Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

Abstract Psoas abscess (PA) is an uncommon disease that has been increasingly reported in recent years. We reviewed patients with PA and analysed their clinical characteristics to improve the understanding of this rare disorder. The study retrospectively reviewed the clinical presentations, microbiology, and outcomes of patients with PA between 2011 and 2021 in Zhejiang Provincial People’s Hospital in China. There were 35 cases out of 23057427 hospitalised adult patients; the mean age was 60 years, and 65.7% of the patients were male. Primary symptoms were typically nonspecific. In all, 17 abscesses were considered secondary, and the most common aetiology was infective spondylitis. The most common causative organism for primary PA was Staphylococcus aureus, followed by Escherichia coli, while for secondary abscesses, there were multiple bacterial species. The overall in-hospital mortality rate was 6%. Secondary PA patients had longer hospital stays (mean, 23 vs. 28 days). PAs, as a serious infectious condition, usually present with nonspecific symptoms and laboratory test results, making early diagnosis difficult. The aetiological profiles differed from those reported in our study. Initial clinical status and subsequent imaging studies can lead to favourable outcomes.

BACKGROUNDInborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase (AMACR) gene mutation.The disease is usually found in children with mild to severe liver disease, cholestasis and poor fat-soluble vitamin absorption.At present, there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption. CASE SUMMARYA 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase, bilirubin and bile acid were abnormally increased; and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid, liver protection and vitamin supplementation, and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved. CONCLUSIONWhen adults have recurrent liver function abnormalities, physicians should be alert to genetic diseases and provide timely treatment.

目的 应用随机森林模型和Logistic回归模型分析新型冠状病毒肺炎(COVID-19)发病的影响因素,为COVID-19防治提供依据.方法 选择2020年1月17日—2月17日浙江省6家医院收治的COVID-19疑似病例为研究对象,通过问卷收集人口学资料、既往基础疾病、流行病学史、临床表现、实验室检测指标和肺部影像学表现等,分别建立随机森林模型和Logistic回归模型分析COVID-19发病的影响因素.结果 共纳入786例COVID-19疑似病例,其中确诊病例336例,占42.75％.随机森林模型分析结果显示,COVID-19发病的影响因素重要性排名前十位依次是白细胞计数正常或减少、胸部影像学表现、淋巴细胞计数减少、聚集性发病、发病前14天内接触来自疫区的发热或呼吸道症状患者、乏力、发病前14天内有疫区旅居史、呼吸困难、鼻塞流涕和肌肉酸痛.多因素Logistic回归模型分析结果显示,发病前14天内有疫区旅居史(OR=8.440,95％CI:4.204～16.944)、发病前14天内接触来自疫区的发热或呼吸道症状患者(OR=2.967,95％CI:1.630～5.402)、聚集性发病(OR=25.164,95％CI:11.833～53.516)、乏力(OR=2.710,95％CI:1.490～4.930)、呼吸困难(OR=5.276,95％CI:2.076～13.410)、肌肉酸痛(OR=14.187,95％CI:1.998～100.730)、白细胞计数正常或减少(OR=1.750,95％CI:1.659～1.852)和胸部影像学表现(OR=6.291,95％CI:4.315～9.171)均与COVID-19存在统计学关联.结论 两种模型的分析结果相似,随机森林模型显示各个因素在COVID-19发病中的重要程度,Logistic回归模型可直观解释不同因素的风险度.

Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients. The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China. A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation. The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia. Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

Liver fibrosis is a necessary stage for patients with chronic hepatitis B to progress to liver cirrhosis or even liver cancer. Detection of early-stage fibrosis is of great clinical significance. Liver biopsy is still the gold standard for hepatic fibrosis, but the clinical application is limited since its invasiveness. Therefore, the method of non-invasive evaluation has been widely used in recent years. This article introduces the progress on serological and imaging evaluation methods of hepatic fibrosis in patients with chronic hepatitis B.

BACKGROUND Primary bone lymphoma (PBL) is an uncommon extranodal disease that represents approximately 1%-3% of lymphomas. Anaplastic lymphoma kinase (ALK) positive anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL. The aim of this report is describe the symptoms, diagnosis, and treatment of primary bone ALK-positive ALCL. CASE SUMMARY A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo. After extensive evaluation, positron emission tomography-computed tomography (CT) examination showed multiple osteolytic bone lesions without other sites lesions. CT-guided biopsy of the T10 vertebral body was performed, and the pathology results showed that neoplastic cells were positive for ALK-1, CD30, and CD3. A diagnosis of primary bone ALK positive ALCL was ultimately made. The patient was in partial response after four cycle soft cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy. CONCLUSION Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement, and lymphoma should be considered in the differential diagnosis of primary bone lesions.

Introduction: Pyogenic liver abscess (PLA) is a serious infectious disease of the liver. Pyogenic liver abscess caused by Fusobacterium nucleatum is extremely rare. Here we report the first case of liver abscess caused by F. nucleatum in China. Case Presentation: The case was a 34-year-old female patient admitted to the hospital due to high fever. The diagnosis of liver abscess was confirmed by imaging studies and liver puncture. We finally confirmed the pathogen as F. nucleatum by next-generation sequencing (NGS). After the targeted anti-infective treatment, the patient recovered and discharged. Conclusions: As a new microbial detection method, NGS can still help in clinical practice. In addition, to improve the positive rate of anaerobic bacteria culture, we should pay attention to avoid contact with air in the process of specimen collection when the pathogenic bacteria are suspected to be anaerobic bacteria.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin's lymphoma. R-CHOP is a protocol for long-term chemotherapy for DLBCL patients. Long-term chemotherapy can lead to low immunity and increase the risk of opportunistic pathogen infections in immunocompromised patients. CASE SUMMARY We report a case of coinfection with Pneumocystis jirovecii (P. jirovecii) and Legionella pneumophila (L. pneumophila) in a patient with DLBCL. The patient was a 40-year-old female who was diagnosed with DLBCL and was admitted due to pulmonary infection. P. jirovecii and L. pneumophila were detected in her bronchoalveolar lavage fluid by hexamine silver staining, isothermal amplification and metagenomic sequencing. CONCLUSION To the best of our knowledge, this is the first case of P. jirovecii and L. pneumophila coinfection found in a DLBCL patient. Clinicians should be aware of the risk of complicated infection in patients undergoing long-term chemotherapy.

Nontuberculous mycobacteria infections present mostly pulmonary characteris-tics. However, the incidence of skin and soft tissue infections caused by nontuberculous mycobacteria has increased in part due to the increased popularity of cosmetic and plastic surgery. Here, we report a case of Mycobacterium agri infection. The patient underwent a one-year course of anti-infection therapy. To the best of our knowledge, this is the first report of a previously healthy patient presenting a skin and soft tissue infection caused by Mycobacterium agri. Clinical personnel should be aware of possible causes of persistent skin and soft tissue infection after cosmetic and plastic surgery.