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Objective:To investigate liver histologic disease in chronic hepatitis B (CHB) patients with normal ALT (Methods:We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtain their 1-year follow up data to establish a predict model of 1-year HBVDNA clearance rate through Logistic regression. Results:The proportion of patient with significant histological disease (significant liver necroinflammation or fibrosis) in the high nALT group was significantly higher than that in the low nALT group (56.43% vs 43.82%, p < 0.001, Table 1). HbeAg negative, GGT and ALT value (OR 0.024, 95% CI 0.011–0.055, p < 0.001; OR 1.027, 95% CI 1.006–1.050, p = 0.013; OR 1.993,95% CI 1.115–3.560, p = 0.020, Table 4) were independent predict factors. High normal ALT is an indicator of 1-year HBVDNA clearance after antiviral treatment. Conclusion: CHB patients with high-normal ALT have significantly higher histological disease rates, and these patients may benefit better from antiviral therapy. We suggest should undergo histological evaluation of liver disease as soon as possible. We also propose these patients should be offered antiviral therapy when feasible.

Background: Talaromycosis is a serious fungal infection which is rare in immunocompetent people. Since its clinical manifestations lack specificity, it is easy to escape diagnosis or be misdiagnosed leading to high mortality and poor prognosis. It is necessary to be alert to the disease when broad-spectrum antibiotics do not work well in immunocompetent patients.Case Presentation: A 79-year-old man was admitted to our Infectious Diseases Department for recurrent fever and cough. Before admission he has been treated with piperacillin-tazobactam, moxifloxacin followed by antituberculous agents in other hospitals while his symptoms were not thoroughly eased. During the first hospitalization in another hospital, he has been ordered a series of examination including radionuclide whole body bone imaging, transbronchial needle aspiration for subcarinal nodes. However, the results were negative showing no neoplasm. After being admitted to our hospital, he underwent various routine examinations. The initial diagnosis was bacterial pneumonia, and he was given meropenem injection and tigecycline injection successively, but there were no improvement of symptoms and inflammatory indicators. In the end, the main pathogen Talaromyces marneffei was confirmed using Metagenomic Next-Generation Sequencing (mNGS), and his clinical symptoms gradually relieved after targeted antifungal treatment using voriconazole.Conclusion: When empirical anti-infective treatment is ineffective, it is necessary to consider the possibility of opportunistic fungal infections on immunocompetent patients. mNGS, as a new generation of pathogenic testing methods, can often detect pathogenic bacteria faster than traditional methods, providing important help for clinical decision-making.

To the Editor,In early December 2019, a novel coronavirus (SARS-CoV-2) was identified in Wuhan. It has been named COVID-19 and to date it has spread to more than 120 countries. It has become a glob...

ObjectivesNo data were available about in-flight transmission of SARS-CoV-2. Here, we report an in-flight transmission cluster of COVID-19 and describe the clinical characteristics of these patients.MethodsAfter a flight, laboratory-confirmed COVID-19 was reported in 12 patients. Ten patients were admitted to the designated hospital. Data were collected from 25th January to 28th February 2020. Clinical information was retrospectively collected.ResultsAll patients are passengers without flight attendants. The median age was 33 years, and 70% were females. None was admitted to intensive care unit, and no patients succumbed through 28th February. The median incubation period was 3.0 days and from illness onset to hospital admission was 2 days. The most common symptom was fever. Two patients were asymptomatic and negative for chest CT scan throughout the disease courses. On admission, initial RT-PCR were positive in 9 patients, however initial chest CT were positive in only half patients. The median lung “total severity score” of chest CT was 6. Notably, “Crazy-Paving” pattern, pleural effusion, and ground-glass nodules were also seen.ConclusionIt is potential for COVID-19 transmission by airplane, but the symptoms are mild. Passengers and attendants must be protected during the flight.

Background Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, Hubei. Aim This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China. Design This study was a retrospective case series. Methods Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. Results and discussion Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5–57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3–8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1–2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia. Conclusions Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.

Nephronectin (NPNT) is a novel extracellular matrix protein and a new ligand of integrin α8β1. Recent studies showed that NPNT is highly expressed in kidney, lung, thyroid, etc, and it may play an important role in many pathological conditions. NPNT is involved in the process of kidney development and acute kidney injury, regulates proliferation and differentiation of osteoblast, and induces the vasculogenesis in vitro. NPNT may play a key role in pathological osteoporosis and therefore be a new therapeutic target of bone diseases. NPNT gene variants are not only associated with lung function, but also potentially implicated in chronic airway diseases development. Moreover, NPNT is also an important factor that mediates pathology of cardiac, epidermis, breast, liver and teeth diseases. In this paper, we reviewed some research progresses on the structure, distribution, physiological and pathophysiological functions of NPNT.

// Naibin Yang 1 , Shanshan Li 2 , Guoxiang Li 1 , Shengguo Zhang 2 , Xinyue Tang 2 , Shunlan Ni 2 , Xiaomin Jian 3 , Cunlai Xu 4 , Jiayin Zhu 5 and Mingqin Lu 2 1 Department of Infection and Liver Diseases, Ningbo First Hospital, Ningbo, China 2 Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China 3 Department of The First Clinical Medical, Wenzhou Medical University, Wenzhou, China 4 Department of Respiration, Lishui People’s Hospital of Wenzhou Medical University, Lishui, China 5 Laboratory Animal Center, Wenzhou Medical University, Wenzhou, China Correspondence to: Mingqin Lu, email: // Keywords : extracellular vesicles, exosomes, miRNA, hepatocellular carcinoma, MSCs Received : April 28, 2016 Accepted : September 28, 2016 Published : October 04, 2016 Abstract Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC. Exosomal miRNAs derived from HCC cells can enhance transformed cell growth in recipient cells by modulating the expression of transforming growth factor-β activated kinase-1(TAK1) and downstream signaling molecules. Furthermore, vacuolar protein sortin 4 homolog A(VPS4A) and insulin-like growth factor(IGF)-1 regulate exosome-mediated miRNAs transfer. Immune cells- derived EVs containing integrin αMβ2 or CD147 may facilitate HCC metastasis. In addition, EVs-mediated shuttle of long non-coding RNAs (lncRNAs), specifically linc- VLDLR and linc-ROR promote chemoresistance of malignant cells. Heat shock proteins (HSPs)-harboring exosomes derived from HCC tumor cells increase the antitumor effect of natural killer (NK) cells, thus enhancing HCC immunotherapy. Indeed, inhibition of HCC tumor growth has been associated with tumor cell-derived exosomes (TEX)-pulsed dentritic cells (DCs). Exosomes are also essential in liver metastasis during colorectal carcinoma (CRC) and pancreatic ductal adenocarcinomas (PDAC). Therefore, as nucleic acid and drug delivery vehicles, EVs show a tremendous potential for effective treatment against HCC.

We report a family cluster of coronavirus disease 2019 (COVID-19) caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a 6-year-old child had no evidence of infection. Among the 8 patients, 1 adult and a 13-month-old infant were asymptomatic, and 1 adult was diagnosed as having severe pneumonia.

Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/ d -galactosamine induced acute liver failure via inhibition of TLR4 pathway.

Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months. Then acute liver injury was induced by combined D-galactosamine and lipopolysaccharide. Six time points were examined before or after acute induction. Liver samples were performed with hematoxylin-eosin and Masson staining; circulatory Treg and Th17 cell frequencies were determined using flow cytometry assays; serum levels of alanine aminotransferase, aspartate aminotransferase, interleukin-10 (IL-10), and interferon-γ (IFN-γ) were examined. Results. In group ACLF, both Th17 cell proportion and IFN-γ level presented upgrade firstly and then descend latter tendency; the trends of Treg cell proportion and IL-10 level were observed to gradually decrease and became stable. Conclusion. The Treg cells played an important role in the immunologic mechanism during the process of ACLF. And the function of Treg cells in ACLF was defective.

Delaminating of composite is one of keys for composite structures. An energy method was used to analyze the fundamental frequency of HT3/5224 carbon fiber reinforced laminated plate in this paper. Different delaminated situations are considered in analysis on vibration of composite based on Kirchhoff theory. The results show that delaminations have a great influence on the fundamental frequency of laminated plate. The discussion shows inner delaminations have more influence on composite laminates than surface delaminations. Different kinds of delaminations can interact each other and the interaction can increase the influence on frequency.

Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF.

Laboratory animals and animal experiments are foundations and important support conditions for life sciences, especially for medical research. The animal experiments have drawn extensive attention from the society because of the ethical issue. This paper takes Wenzhou Medical University as an example to give a brief introduction to the ethical review about laboratory animals in the university so as to further draw attention and concerns from the public about the ethical issue of laboratory animals. We successively introduce its scientific projects, nurturing environment and ethical review of laboratory animals.

Activation of hepatic stellate cells (HSCs) is a pivotal event during hepatic fibrogenesis. Activated HSCs are the main source of collagen and other extracellular matrix (ECM) components, and emerging antifibrotic therapies are aimed at preventing ECM synthesis and deposition. MicroRNAs (miRNAs) have been demonstrated to exert regulatory effects on HSC activation and ECM synthesis. In the present study, the HSC‑T6 rat hepatic stellate cell line was transiently transfected with a miRNA (miR)‑203 mimic, which is an artificial miRNA that enhances the function of miR‑203, with a miR‑203 inhibitor or with a scramble miRNA negative control. mRNA and protein expression levels of collagen (COL) 1A1, COL3A1, α‑smooth muscle actin (α‑SMA) and mothers against decapentaplegic homolog 3 (SMAD3) were assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The interaction between miR‑203 and the 3'‑untranslated region (UTR) of SMAD3 mRNA was examined using a dual‑luciferase reporter assay. The proliferative capabilities of activated HSCs were measured using an MTT assay. The present results demonstrated that the mRNA and protein expression levels of COL1A1, COL3A1, α‑SMA and SMAD3 were significantly upregulated following transfection of HSC‑T6 cells with the miR‑203 inhibitor. Conversely, COL1A1, COL3A1, α‑SMA, and SMAD3 mRNA and protein expression appeared to be downregulated in rat HSCs transfected with miR‑203 mimics. Notably, the inhibition of miR‑203 expression was revealed to promote HSC proliferation, whereas increased miR‑203 expression suppressed the proliferative capabilities of HSC‑T6 cells. Furthermore, SMAD3 was revealed to be a direct target of miR‑203. The present study suggested that miR‑203 may function to prevent the synthesis and deposition of ECM components, including COL1A1, COL3A1 and α‑SMA, and to inhibit the proliferation of HSCs through a SMAD3‑dependent mechanism. Therefore, it may be hypothesized that miR‑203 has potential as a novel target for the development of alternative therapeutic strategies for the treatment of patients with hepatic fibrosis in clinical practice.

To the EditorWe read with interest the recent article in this journal by Yao et al. [1] on cryptococcal meningitis (CM). In their study, the response rate to voriconazole was more favourable than t...

It has been reported that hypereosinophilic syndrome may be induced by antituberculosis drugs. We herein report the case of a 43-year-old man who had been on antituberculosis drugs for two months to treat tuberculous meningitis. During therapy, he suffered from drug rash with eosinophilia and systemic symptoms (DRESS) presenting as acute eosinophilic myocarditis, as confirmed on a histopathologic examination. According to the patient's medication history, clinical features and accessory examination findings, the eosinophilic myocarditis was thought to be possibly induced by isoniazid. Although further investigations are needed to confirm causality, isoniazid may be added to the list of drugs with the potential to cause DRESS syndrome.

The aim of this study was to elucidate the effects of zedoary turmeric oil (ZTO) on P450 activities (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) in rats with liver cirrhosis induced by thioacetamide (TAA). For the induction of liver cirrhosis, rats were given TAA in their drinking water at a concentration of 0.03% for consecutive 5 weeks and then 0.04% for the next consecutive 5 weeks throughout the establishment of cirrhosis. Then the cirrhotic rats were ip given saline, ZTO 100, 200 and 400 mg/kg, respectively, once daily for 2 weeks. When cirrhosis model was established at week 10, all rats of five groups were administered intragastrically with 15 mg/kg phenacetin, 0.6 mg/kg tolbutamide, 15 mg/kg omeprazole, 15 mg/kg bupropion, 15 mg/kg metoprolol, and 10 mg/kg midazolam. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The degree of liver cirrhosis was assessed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the model group increased by approximately 4-fold, and a decreased level of albumin (Alb) was also observed, as compared to the control group (P < 0.05). However, ZTO was found to reverse those changes of serum levels observed in the model group, and the 200 mg/kg ZTO treatment group showed the most obvious reverse tendency with significantly decreased ALT, AST and increased Alb levels (P < 0.05). The results indicated that ZTO with the dose of 100 mg/kg could inhibit the activities of CYP450 isoforms CYP2C9 and CYP2D6 in vivo in cirrhotic rats induced by TAA, while ZTO with the dose of 400 mg/kg could induce the activity of CYP2C19 in vivo in cirrhotic rats induced by TAA. However, ZTO showed no influence on cirrhotic rat hepatic CYP1A2, CYP2B6 and CYP3A4 activity in vivo. This has certain guiding significance to clinical treatment.