Uncontrollable noncompressible bleeding has always been a major cause of death and disability among civilians and military personnel. Herein, a biodegradable, self-gelling protease-grafted alginate dressing was developed for efficient noncompressible bleeding control. The hemostatic dressing was fabricated through a high-degree sodium ion exchange of calcium alginate fibers, followed by covalent grafting of trypsin via carbodiimide chemistry. This design confers exceptional swelling capacity and rapid gelation within seconds upon blood contact, forming a physical barrier. The grafted trypsin establishes an artificial coagulation pathway independent of endogenous factors, significantly shortening in vitro clotting times. Moreover, it promotes adhesion and aggregation of red blood cells and platelets, accelerating clot formation and increasing the clot strength. In a rabbit liver injury model, the dressing achieved hemostasis within 70 s, significantly reducing blood loss and promoting wound healing compared to commercial SURGICEL while demonstrating excellent biocompatibility and biodegradability. The protease-grafted alginate dressing exhibited high robustness against high-temperature treatment, maintaining its high procoagulant activity in vitro for over 55 days at 47 °C.

Rapid and effective bleeding control is essential for saving lives from severe hemorrhage. Currently, expandable hemostatic materials are in urgent demand for narrow and deep wounds because they can be quickly packed into a wound cavity and expand internally to generate pressure that promotes hemostasis. In this work, a zeolite-poly(vinyl alcohol) (PVA) composite sponge was first prepared by decorating zeolite powders onto a commercial medical PVA sponge, and it was further fabricated into small tablets in a compressed state. The small tablets can be easily loaded inside a syringe-like applicator for rapidly injecting into deep wounds in less than 3 s, and they can quickly expand six times in less than 30 s when they come into contact with blood. This material shows outstanding hemostatic efficiency and excellent biosafety. In a New Zealand rabbit severe femoral artery hemorrhage model, the short average hemostasis time (123 s) and the small total blood loss (9.9 g) for the zeolite-PVA sponge group clearly demonstrate its outstanding hemostatic efficiency, compared to the commercial Celox sponge group (220 s and 22.9 g) and the gauze group (333 s and 28.5 g). Consequently, the timely and effective hemostasis led to a 100% survival rate for the zeolite-PVA sponge group in this severe femoral artery hemorrhage model. On the contrary, the survival rates of the gauze group and the Celox sponge group were only 67% and 83%, respectively. This rapidly expandable zeolite-PVA sponge material provides a promising solution for meeting the challenge of massive hemorrhage in narrow and deep wounds.

As immunotherapy gains increasing attention and clinical application, the immune modulation therapy has been widely used in the treatment of infectious and critical diseases. Clinical evidence has been accumulated for application of thymosin alpha 1 (T alpha 1), a classical immune modulator, in related domains. The National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases and other institutions invited multidisciplinary experts to develop this expert consensus on clinical application of T alpha 1 in infectious diseases and critical care medicine. Based on the latest domestic and international research findings and considering relevant factors, including economics, patient preferences and values, tradeoffs, accessibility, fairness and acceptability, the consensus assesses the quality levels of current evidence and forms 10 recommendations on the application of T alpha 1 in treatment of liver diseases, viral infections, bacterial infections and critical illnesses. This consensus aims to enhance understanding of T alpha 1 and improving its standardized application for clinicians.

Wound treatment is a complex and lengthy process that involves rapid hemostasis in the early stage and the prevention of bacterial infection in the later stage. Generally, these two functions are separately achieved by different materials or medicines, thereby causing a lot of inconvenience and pain to patients. In this work, four calcium-copper-based zeolites (CaCuZ) with zeolite P, Y, X, and A structures were fabricated from corresponding sodium-based zeolites via ion exchange. Among these materials, the material with a zeolite P structure possesses better hemostatic performance than those with zeolite X and zeolite Y structures, and it shows improved antibacterial performance compared with the materials containing zeolite A and zeolite X structures. When the copper content of the CaCuZ material with the zeolite P structure is in the range of 0.64-6.30 mg g-1, the clotting time of blood plasma is less than 2.5 min, the bacteriostasis rates against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are higher than 95%, and there is no obvious cytotoxicity towards 3T3 cells. A satisfactory balance in the clotting time, bacteriostasis, and cytotoxicity is achieved in this material, and the material integrates excellent hemostatic and antibacterial properties, offering great application prospects in wound treatment.

This work aims to explore the long-term prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). In this prospective study, eligible inpatients with HBV-ACLF are enrolled and followed up from December 2012 to February 2023, for clinical events, laboratory tests at least every 6 months. Overall, the survival rates at 28 days, 90 days, 1 year, 5 years, and 8 years are 64.7%, 48.8%, 46.1%, 43.8%, and 42.2%, respectively. Among the 8-year mortality and liver transplant cases, ACLF survivors (who survived over 90 days) accounted for 7.8% (9/115). Among 101 patients who survived for more than 90 days, 97.9% of patients achieve virologic response at 1 year. For HBeAg-positive patients, the HBeAg seroconversion are 25.5%, 63.6%, and 76.9% at 1, 5, and 8 years, respectively. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR, white blood cell count, and albumin levels gradually improve within the first year. Fibrosis biomarkers APRI, FIB-4 and Chitinase-3-like protein 1 (CHI3L1) levels decreases within the first 5 years. The Cox proportional hazards regression reveal that high total bilirubin (HR = 1.008, p = 0.021) is the independent risk factor for 8-year survival of ALCF survivors. The 90-day period following of HBV-ACLF represented a critical juncture for long-term prognosis, revealing favorable outcomes beyond this timeframe.

Achieving timely and effective hemorrhage control is imperative for the survival of individuals with severe bleeding. Hemostatic materials, by enhancing the natural cell-based coagulation response, are essential tools in modern and military medical practice for controlling bleeding, especially in emergency and surgical settings. Here, we report a new type of composite hemostatic material with two different aluminosilicate-based components, kaolin and zeolite, which synergistically work together in different stages of the coagulation cascade reactions. Kaolin can effectively activate the clotting factor FXII in the early stage, and zeolite can accumulate and assemble FXa and FVa on its surface and thereafter lead to the formation of highly active thrombin in the later stage. The synergistic action mechanism between kaolin and zeolite significantly boosts the levels of FXIIa and FXa, and it also greatly enhances plateau thrombin activity. For practical application, a kaolin-modified zeolite gauze is fabricated, and it demonstrates excellent hemostatic effectiveness. Compared to the combat gauze currently used in front-line treatment, it reduces blood loss by 75% and shortens hemostasis time by 33% in a rabbit femoral artery injury model. In addition, this kaolin-zeolite gauze has no heat release problem and a nearly zero particle shedding rate, which greatly decreases the safety risk compared to current commercial inorganic-based hemostatic gauzes.

Objective:To investigate the long-term safety and efficacy of autologous peripheral blood stem cell transplantation (APBSCT) in treating decompensated hepatitis B cirrhosis.Methods:In this study, a retrospective analysis was conducted on a cohort of 84 patients diagnosed with decompensated hepatitis B cirrhosis between January 2011 and December 2012. The patients were categorized into two groups based on their treatment approach: the transplantation group, consisting of 34 cases who received APBSCT in addition to medical treatment, and the comprehensive medical treatment (CMT) group, comprising 50 cases who solely received CMT. EPI Data software was used for data input and verification. Survival curves were drawn by Kaplan-Meier method and analyzed by log-rank test. Paired t test and independent sample t test were used for intra-group and inter-group mean comparison of measurement data, respectively. The Mann-Whitney U test is used for non-normally distributed data.Results:After the ten-year follow-up period, it was found that overall survival (OS) in the transplantation group was markedly higher than that in the CMT (56% vs. 16%, P < .001). Albumin (ALB), prothrombin time (PT), and indocyanine green retention at 15 min (ICG R15) were significantly improved in sequence at 4 to 12 weeks of early treatment in APBSCT group; subsequently, the Acoustic radiation force impulse (ARFI) index and spleen length significantly decreased at 48 weeks. Compared with the CMT group, ALB and PT levels in the APBSCT group continued to recover and eventually stabilize at normal or low-risk levels at subsequent follow-ups up to 8 years. The ten-year prevalence of hepatocellular carcinoma (HCC) in the APBSCT group was markedly lower than that in the CMT group (26% vs. 62%; P = .025). Moreover, APBSCT significantly reduced ascites (χ2 = 6.997, P = .041) and was not associated with any significant adverse events during APBSCT. Based on clinical evidence, APBSCT is a safe and effective treatment for decompensated hepatitis B cirrhosis, resulting in a favorable long-term prognosis with no significant adverse events.Conclusions:APBSCT is a relatively safe and effective treatment for decompensated hepatitis B cirrhosis.

Acute-on-chronic liver failure (ACLF) is a critical illness with high mortality. Herein, we developed and validated a new and simple prognostic nomogram to predict 90-day mortality in hepatitis B virus-related ACLF (HBV-ACLF) patients. This single-center retrospective study collected data from 181 HBV-ACLF patients treated between June 2018 and March 2020. The correlation between clinical data and 90-day mortality in patients with HBV-ACLF was assessed using univariate and multivariate logistic regression analyses. Multivariate logistic regression analysis showed that age (p = 0.011), hepatic encephalopathy (p = 0.001), total bilirubin (p = 0.007), international normalized ratio (p = 0.006), and high-density lipoprotein cholesterol (p = 0.011) were independent predictors of 90-day mortality in HBV-ACLF patients. A nomogram was created to predict 90-day mortality using these risk factors. The C-index for the prognostic nomogram was calculated as 0.866, and confirmed to be 0.854 via bootstrapping verification. The area under the curve was 0.870 in the external validation cohort. The predictive value of the nomogram was similar to that of the Chinese Group on the Study of Severe Hepatitis B score, and exceeded the performance of other prognostic scores. The prognostic nomogram constructed using the factors identified in multivariate regression analysis might serve as a beneficial tool to predict 90-day mortality in HBV-ACLF patients.

Objective:To compare the efficacy and safety of omacycline with meropenem plus linezolid in the treatment of patients with pulmonary infection.Methods:The clinical data of 58 patients with pulmonary infection admitted to the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou Red Cross Hospital and Jiande First People’s Hospital from December 2021 to May 2022 were retrospectively analyzed. The patients were divided into the omacycline group ( n=29) and the meropenem combined with linezolid group (combined group, n=29). The omacycline group was given intravenous omacycline 200 mg or 100 mg, q. d, and the combined group was given intravenous meropenem (1 000 mg, t.i.d) and linezolid (600 mg, b. i.d). The clinical efficacy and drug-related adverse events of two groups were observed. SPSS 22.0 statistical software was used for data analysis. Results:In the omacycline group, 8 cases (27.6%, 8/29) were cured, 19 cases (65.5%, 19/29) were improved, and 2 cases (6.9%, 2/29) were worsened. In the combined group, 1 case (3.4%, 1/29) was cured, 26 cases (89.7%, 26/29) were improved, and 2 cases (6.9%, 2/29) died. There was a statistically significant difference between the two groups ( χ2=6.533, P=0.038). The respiratory failure occurred in 3 cases (10.3%, 3/29) of the omacycline group and 5 cases (17.2%, 5/29) of the combined group ( χ2=0.580, P=0.446). In those patients who were cured or improved, the median time from treatment initiation to disease remission was 3.0 (2.0, 5.5) d in the omacycline group and 5.0 (4.0, 6.0) d in the combined group ( Z=-2.122, P=0.034). There was no significant difference in the incidence of adverse reactions between the two groups [6.9% (2/29) vs. 13.8% (4/29), χ2=0.744, P=0.389]. Conclusion:Omacycline exhibits a good efficacy and safety in the treatment of patients with pulmonary infection, which may be prioritized for the treatment of pulmonary infections.

肝衰竭是多种因素引起的严重肝脏损害,导致合成、解毒、代谢和生物转化功能严重障碍或失代偿,出现以黄疸、凝血功能障碍、肝肾综合征、肝性脑病、腹水等为主要表现的一组临床症候群.我国引起肝衰竭的主要病因是肝炎病毒(尤其是HBV),其次是药物及肝毒性物质(如酒精、化学制剂等).儿童肝衰竭还可见于遗传代谢性疾病.

Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decom-pensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4％)patients with ACLF-1,64(30.2％)with ACLF-2,and 73(34.4％)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8％),followed by hepatic encephalopathy(57.1％),bacterial infections(48.1％),hepatorenal syndrome(22.2％)and gastrointestinal bleeding(11.3％).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P＜0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P＜0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic mod-els(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.

血吸虫病是由血吸虫寄生于人体所致的一类严重寄生虫病,危害人类的身体健康和生命安全.经过数十年、几代人的努力,目前在我国,日本血吸虫病的流行表现为低度感染,但由于传染源、传播途径和易感人群的普遍存在,在全国范围内彻底消灭血吸虫病仍然任重而道远.因此,本文将主要从"国内诊治"和"外防输入"两个方面对血吸虫病的诊治和预防进行综述,以期引起广大人民群众的重视,为血吸虫病的防控工作提供借鉴.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.

ABSTRACT Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a critical disease with high mortality risk. Low triiodothyronine syndrome (LT3S) is associated with various severe acute and chronic diseases. We investigated the relationship between LT3S and poor prognosis in patients with HBV-ACLF. Research design and methods A total of 198 patients with HBV-ACLF were enrolled between January 2018 and March 2019. We screened for independent risk factors for 28-day mortality using univariate and multivariate logistic regression analyses. Spearman’s correlation analysis was used to evaluate the correlation between LT3S and the poor prognostic parameters of HBV-ACLF. Results LT3S was an independent risk factor for 28-day mortality in HBV-ACLF patients (odds ratio: 4.035, 95% confidence interval 1.117–14.579; p = 0.033). The death group had a lower serum FT3 level (Z-value = 2639.000, p < 0.001). Serum FT3 levels were negatively correlated with age, C-reactive protein, international normalized ratio, and neutrophil count but positively correlated with lymphocyte count. A negative correlation between FT3 and various prognostic scores was observed, indicating that a low FT3 level was closely related to a poor prognosis. Conclusions LT3S was an independent risk factor for 28-day mortality and was correlated with poor prognosis in patients with HBV-ACLF.

白蛋白是人体血浆中含量最高的蛋白质,其胶体功能及非胶体功能对于机体具有多方面调节作用.终末期肝病患者体内因白蛋白合成减少、丢失、功能异常而导致的病情恶化及相关并发症在使用人血白蛋白治疗后大多可获得一定程度的缓解,甚至好转.本文结合近期国内外的研究,探讨了人血白蛋白在终末期肝病中的应用及临床疗效,提出有效白蛋白含量监测有可能成为终末期肝病预后及治疗的新指标.

Objective:To investigate the clinical characteristic of patients infected with influenza A virus, and evaluate the influencing factors of influenza A pneumonia.Methods:The clinical characteristics and treatment of 160 inpatients with influenza A virus infection from 2016 to 2020 in the First Affiliated Hospital of Zhengjiang University School of Medicine were retrospectively analyzed, and the influencing factors of influenza A pneumonia were analyzed by multiple Logistic regression.Results:The main symptom of influenza A patients was fever (159 cases, 99.38%). There were 121 cases(75.63%) complicated with influenza A pneumonia and 157 cases(98.13%) treated with antiviral therapy. The factors influencing the complications of pneumonia in patients with influenza A were lactate dehydrogenase(LDH) ( OR=1.010, 95% CI: 1.003-1.017) and C-reactive protein(CRP) ( OR=1.091, 95% CI:1.034-1.150). Conclusions:Fever is the most common symptom of influenza A, and viral pneumomia is a common complication. CRP and LDH can be used as reference indexes to evaluate the severity of influenza A patients.

ABSTRACT Changes in intestinal flora affect the health and cause metabolic diseases of the host. The extent to which the impact of different changes in intestinal flora would have on the metabolism of an individual has not been reported. This study aims to investigate the effect of different changes in intestinal flora on the metabolism of Sprague–Dawley (SD) normal rats’ individuals. Forty-eight SD rats were randomly divided into 6 groups (8 rats per group), which were treated with normal saline, probiotics, nonpathogenic Escherichia coli, Salmonella enteritidis, gentamicin, and magnesium sulfate, respectively. After 7 days, the ileum of each group of rats was collected and real-time polymerase chain reaction was used to analyze the composition of intestinal flora. And gas chromatography/mass spectrometry (GC/MS) was used to analyze plasma metabolic profile. The results revealed that the decrease in alanine content in the probiotics group was statistically significant, while the alanine content in the nonpathogenic Escherichia group increased significantly. Alanine, leucine, isoleucine, and serine decreased significantly in the Salmonella group. Proline and butyric acid decreased significantly in the gentamicin group. The principal component analysis showed significant differences in the Salmonella group compared with other test groups. Overall, the most significant metabolic changes were observed in SD rats in the Salmonella group, while a great similarity was observed in the probiotics, Escherichia group, and gentamicin groups compared with the normal group. Changes in intestinal flora had a certain impact on the metabolism in SD rats, especially on amino acid levels.

Objective Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. Methods Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). Results The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. Conclusions This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

To the Editor : Cirrhotic patients usually require multiple hospitalizations due to upper gastrointestinal hemorrhage, abdominal infection, and hepatic encephalopathy. These patients need long-term hospital stay, and long-term application of proton pump inhibitors and antibiotics, which may result in Clostridium difficile infection（CDI） [1]. To our best knowledge, Clostridium difficile colonization（CDC） is the major risk factor for the pathogenesis of CDI.

Background: Cholestasis may lead to hepatic cirrhosis and a longer hospital stay. A part of the patients with cholestasis requires liver transplantation. However, most of the treatment efficiency of cholestatic hepatitis (CH) is not satisfactory. For the patients with severe CH after artificial liver support, there was a lack of systemic evaluation on the treatment efficiency of double plasma molecular absorption system (DPMAS) for acute severe CH. Objective: We aim to investigate the treatment efficiency of DPMAS on acute severe CH. Methods: This retrospective study involved 309 cases diagnosed with acute severe CH admitted to the First Affiliated Hospital, Zhejiang University. We compared the prognosis of patients received standard medical therapy (SMT) and SMT + DPMAS. Besides, the effects of DPMAS on total bilirubin (TBIL) and prothrombin time (PT) were investigated. Results: DPMAS could significantly reduce the requirements for liver transplantation in the CH patients. After DPMAS therapy, significant decline was noticed in the TBIL, direct bilirubin (DBIL), total bile acid, and cholesterol. The baseline ratio of neutrophil showed significant elevation in the patients received 4 or more DPMAS compared with those received less DPMAS. Conclusions: DPMAS could significantly eliminate the necessity of liver transplantation. The artificial liver support system should be conducted to bring down the bilirubin level and the ratio of cases with severe conditions. In general, DPMAS should be preferred as an artificial liver support therapy for the patients with acute severe CH.