ObjectiveTo investigate the variation of drug resistance genes in human immunodeficiency virus (HIV)-1 strains in Huzhou City, Zhejiang Province, so as to provide a basis for guiding the adjustment of treatment plans for ADIS patients or patients infected with HIV. MethodsA total of 555 samples were collected from 396 newly diagnosed HIV/AIDS patients who did not receive antiviral treatment from 2021 to 2023, in addition to 159 HIV/AIDS patients who received antiviral treatment for at least twelve months but failed during the same period.Reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (nested PCR) were used to amplify the pol region gene of HIV-1. Lastly, the sequenced data were submitted to the HIV resistance database of Stanford University in the United States for resistance gene mutation analysis. ResultsDrug resistance mutations were detected in samples from 97 newly diagnosed HIV/AIDS patients and 77 patients with failed treatment, with the main subtypes being CRF01AE and CRF07-BC. The mutation rates of drug resistance genes in the patients untreated and patients with failed treatment were 24.49% (97/396) and 48.43% (77/159), respectively. Drug resistance gene mutations against protease inhibitor (PI), nucleotide reverse transcriptase inhibitor (NRTI), and non-nucleoside reverse transcriptase inhibitor (NNRTI) were detected both in the untreated and failed treatment group. The drug resistance rates of untreated and failed treatment patients were 10.61% (42/396) and 45.28% (72/159), respectively. ConclusionThe pre-treatment drug resistance rate of HIV-1 strains in Huzhou City is at a moderate level, and which is at a relatively low level nationwide after antiviral treatment. The resistance genes in the region exhibit diverse and complex characteristics, and the prevalence of drug resistance is in the process of upward and evolution compared to the monitoring results in the previous years. It is necessary to continue to monitor the occurrence and development of drug resistant strains, and to adjust treatment plans in time to prevent the occurrence of transmissible drug resistance.

Objective To summarize the short-term results of valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) in the treatment of bioprosthetic valve failure after aortic valve replacement. Methods We reviewed the clinical data of patients who underwent ViV-TAVI from 2021 to 2022 in the First Affiliated Hospital of Zhengzhou University. The valve function was evaluated by echocardiography before operation, immediately after operation and 3 months after operation. The all-cause death and main complications during hospitalization were analyzed. Results A total of 13 patients were enrolled, including 8 males and 5 females with a mean age of (65.9±8.5) years, and the interval time between aortic valve replacement and ViV-TAVI was (8.5±3.4) years. The Society of Thoracic Surgeons mortality risk score was 10.3%±3.2%. None of the 13 patients had abnormal valve function after operation. The mean transvalvular pressure gradient of aortic valve was decreased (P<0.001), the peak flow velocity of aortic valve was decreased (P<0.001), and the left ventricular ejection fraction was not changed significantly (P=0.480). There were slight perivalvular leakage in 2 patients and slight valve regurgitation in 3 patients. Three months after operation, the mean transvalvular pressure difference and peak flow velocity of aortic valve in 12 patients were significantly decreased compared with those before operation (P≤0.001). Conclusion This study demonstrates that ViV-TAVI for the treatment of bioprosthetic valve failure after aortic valve replacement is associated with favorable clinical and functional cardiovascular benefits, the short-term results are satisfactory.

BACKGROUND: Lead is a persistent inorganic environmental pollutant with global implication for human health. Among the diseases associated with lead exposure, the damage to the central nervous system has received considerable attention. It has been reported that long-term lead exposure increases the risk of meningioma; however, the underlying mechanism remains poorly understood. Clinical studies have indicated that loss-of-function and mutations in the neurofibromin-2 (NF2) gene play a crucial role in promoting meningioma formation. METHODS: The effect of Pb on meningioma were tested in-vitro and in-vivo. Two human meningioma cell lines were used in this study, including NF2-wildtype IOMM-Lee cell and NF2-null CH157-MN cell. Cell viability, cell cycle and cell size were examined after Pb exposure. The expression of Merlin, mammalian sterile 20-like kinases 1 and 2 (MST1/2) and Yes-associated protein (YAP) from these two meningioma cells were analyzed by Western blot. A xenograft mouse model was constructed by subcutaneous injection of IOMM-Lee meningioma cells. RESULTS: This study demonstrated that treatment with lead induce dose-dependent proliferation in IOMM-Lee cell (with an EC₅₀ value of 19.6 µM). Moreover, IOMM-Lee cell exhibited augmented cell size in conjunction with elevated levels of phosphorylated histone H3, indicative of altered cell cycle progression resulting from lead exposure. However, no significant change was observed in the CH157-MN cell. Additionally, the Merlin-Hippo signaling pathway was inactivated with decreased Merlin and phosphorylation levels of MST1/2 and YAP, leading to increased YAP nuclear translocation in IOMM-Lee cells. However, there was no change in the Merlin-Hippo signaling pathway in CH157-MN cells after lead treatment. The administration of Pb resulted in an acceleration of the subcutaneous IOMM-Lee meningioma xenograft growth in mice. CONCLUSIONS Overall, the current study elucidates the potential mechanism by which lead exposure promotes the proliferation of meningioma with NF2 expression for the first time.
Meningioma/genetics* ; Neurofibromin 2/genetics* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Signal Transduction/drug effects* ; Mice ; Hippo Signaling Pathway ; Lead/adverse effects* ; Cell Line, Tumor ; Protein Serine-Threonine Kinases/genetics* ; Meningeal Neoplasms ; Environmental Pollutants/adverse effects* ; Female

ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

Cuproptosis is a new type of cell death that depends on intracellular copper accumulation to trigger the aggregation of mitochondrial lipoacylated protein and the degradation of iron-sulfur cluster protein,with a different mechanism of action from autophagy,ferroptosis,pyroptosis,and necroptosis.Cuproptosis is closely association with the development of liver cancer and resistance to antitumor drugs,as well as the progression of various liver diseases such as hereditary liver diseases,nonalcoholic fatty liver disease,viral hepatitis,and liver cirrhosis.This article summarizes the mechanism of cuproptosis and its role in liver diseases,in order to provide a reference for further research and treatment of liver diseases.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Fetal structural anomalies and birth defects are primarily caused by genetic variants such as chromosomal number abnormalities, copy number variations (CNV), single nucleotide variants (SNV), and small insertions and deletions (indel). Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) as an emerging technology for genetic disease diagnosis can detect the aforementioned types of variants. In recent years, high-depth WGS (> 30×) for prenatal diagnosis has also become available, and proved to be practical for unraveling the genetic etiology of fetal developmental abnormalities. To fascilitate clinical practice, test development and preliminary implementation of WGS for diagnosing fetal structural anomalies, we have formulated a consensus over the application of WGS in prenatal diagnosis by compiling previously published consensuses, guidelines, and research findings to provide a guidance on data analysis, reporting recommendations, and consultation of prenatal WGS results.