Objective: To investigate the knowledge of hepatitis C prevention and treatment and related factors among two groups of female sex workers (FSW) and men who have sex with men (MSM) in the Xizang Autonomous Region (Xizang) to provide a basis for the subsequent development of Hepatitis C publicity and education strategies. Methods: From August to September 2021, a special survey was conducted among 1 244 FSW and 234 MSM in 5 districts (counties) of 4 regions in Xizang. A one-on-one face-to-face questionnaire survey was adopted, and the χ² test and logistic regression were used to analyze the related factors of awareness of hepatitis C prevention and treatment among FSW and MSM. Results: The awareness rates of hepatitis C prevention and treatment knowledge among FSW and MSM were 35.0% (436/1 244) and 11.1% (26/234), respectively. Multivariate logistic regression analysis revealed that the positive related factors of FSW' awareness of hepatitis C prevention and treatment knowledge among those who had high school or technical secondary school education (aOR=4.72, 95%CI: 3.30-6.74) and college education or above (aOR=2.24, 95%CI: 1.58-3.18), those who experienced self-perceived risk of HCV infection (aOR=1.87, 95%CI: 1.43-2.45), negative related factors included married or cohabiting (aOR=0.58, 95%CI: 0.35-0.95), divorce or windowless (aOR=0.44, 95%CI: 0.27-0.72), no condom was used in the most recent commercial sexual activity (aOR=0.54, 95%CI: 0.43-0.69). The positive related factors of MSM's awareness of hepatitis C prevention and treatment knowledge were over 40 years old (aOR=8.65, 95%CI: 3.19-23.42) and having a self-perceived risk of HCV infection (aOR=6.25, 95%CI: 2.50-15.61). Conclusions: The awareness rate of hepatitis C prevention and treatment among FSW and MSM was relatively low in Xizang in 2021 and urgently needs to be improved. It is necessary to formulate targeted publicity strategies based on the characteristics of these two groups of people, increase publicity efforts, and expand the coverage of knowledge publicity to popularize key points about the clinical manifestations, treatment options, and transmission routes of hepatitis C, and carry out necessary warnings and education.
Humans ; Male ; Hepatitis C/therapy* ; Health Knowledge, Attitudes, Practice ; Surveys and Questionnaires ; Sex Workers/psychology* ; Homosexuality, Male ; Female ; Adult ; China ; Young Adult ; Middle Aged ; Logistic Models

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

This article provides an interpretive review of the "2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation", which was updated and published by the American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) based on the latest clinical evidence. It delves into the classification and management strategies for atrial fibrillation (AF), grounded in the most current evidence-based medical research. The guideline offers significant updates in various aspects such as the definition and staging of AF, clinical evaluation and treatment, modification of risk factors, prevention of thromboembolism, and management of specific populations. Notably, the introduction of a new staging model for AF and corresponding management strategies stands out, underscoring the importance of prevention and early intervention. This article focuses on the three pillars of integrated AF management—stroke risk assessment, modification of risk factors, and management of specific patient groups, in addition to rate and rhythm control, analyzes their substantial significance in clinical practice and guides clinicians in providing more precise treatment.

Meropenem is one of the most widely used special-grade antimicrobial agents in the treatment of neonatal sepsis.However,its irrational use has led to an increasingly severe problem of bacterial multidrug resistance.The guideline was developed following standardized methods and procedures,and provides 12 recommendations specifically addressing 9 clinical issues.The recommendations cover various aspects of meropenem use in neonates,including timing of administration,recommended dosage,extended infusion,monitoring and assessment,antimicrobial adjustment strategies,treatment duration,and treatment strategies for carbapenem-resistant Enterobacteriaceae infections.The aim of the guideline is to provide evidence-based recommendations and guidance for the rational use of meropenem in neonates with sepsis.[Chinese Journal of Contemporary Pediatrics,2024,26(2):107-117]

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective    To compare the in-hospital outcomes of transapical transcatheter aortic valve replacement (TA-TAVR) for bicuspid aortic valve (BAV) patients and tricuspid aortic valve (TAV) patients. Methods    Patients (including BAV and TAV patients) who underwent TA-TAVR with the J-ValveTM in West China Hospital from July 2014 to July 2020 were included consecutively. The clinical outcomes of the patients were analyzed. Results    A total of 354 patients were included in the study, 75 in the BAV group and 279 in the TAV group. There were 229 males and 125 females with a mean age of 72.2±6.0 years. No death occurred during the procedure, and the overall technical success rate was 97.7%. The all-cause in-hospital mortality rate was 1.4%. Twenty (26.7%) patients with BAV and 46 (16.5%) patients with TAV had mild or higher perivalvular leaks immediately after the procedure. No patients with BAV required permanent pacemaker implantation postoperatively, while 13 (4.7%) TAV patients required permanent pacemaker implantation, with an overall pacemaker implantation rate of 3.7%. One (1.3%) BAV patient and 7 (2.5%) TAV patients developed acute kidney injury postoperatively. One (1.3%) BAV patient and 1 (0.4%) TAV patient developed peri-operative myocardial infarction. The average postoperative hospital stay was 7.6±3.6 d for BAV patients and 8.6±6.1 d for TAV patients. There was no statistical difference in primary or secondary in-hospital outcomes between BAV and TAV patients (P>0.05). Conclusion    Compared to TAV patients, BAV patients have similar in-hospital outcomes, with a low incidence of adverse clinical outcomes, which provides preliminary evidence for its implementation in Chinese patients with a high proportion of BAV.