Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective: To investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

Circulating tumor DNA(ctDNA)is a kind of cell-free DNA derived from tumors,which carries comprehensive tumor genetic information;Recent studies have found that ctDNA detection can play a role in the early diagnosis,targeted therapy,and prediction of recurrence in tumors.Human papillomavirus(HPV)-associated gynecological malignancies include most cervical cancer,some vulvar cancer,and vaginal cancer.High-risk HPV long-term infection and integration with cell genome are important causes of these cancers.Studies found that the use of ctDNA detection technology to dynamically monitor changes in HPV-ctDNA can provide valuable information for the clinical management and prognosis of these cancers.Thus,HPV-ctDNA is expected to become an biomarker for HPV-associated tumors.

Objective To construct SpyCatcher-mi3 nanoparticle vaccine delivery vectors,evaluate their role in enhancing the immunogenicity of the ovalbumin CD8+T-cell epitope peptide,OVA257-264,and determine its protective effect in a model which mice were immunized and subcutaneously challenged with E.G7-OVA tumor cells.Methods SpyCatcher-mi3 proteins were expressed by E.coli and purified by affinity chromatography and anion exchange chromatography sequentially.OVA257-264-SpyTag peptide was obtained by synthesis.The OVA257-264-mi3 nanoparticles were produced by the SpyTag/SpyCatcher system.The toxicity of OVA257-264-mi3 was evaluated using hemolysis assay,CCK-8 assay and mouse experiment.A total of 42 female SPF-grade C57BL/6 mice(6～8 weeks old,18～20 g)were randomly divided into OVA257-264-mi3,OVA257-264,and control groups,with 14 mice in each group.Then the mice in each group were immunized on days 0,14 and 28.In 14 d after the last immunization,the amounts of spot-forming cells(SFCs,indicating IFN-γ secreting cells in splenic lymphocytes)were determined using ELISpot assay to evaluate their immunogenicity.After the immunized mice were subcutaneously implanted with E.G7-OVA tumor cells,the antitumor effect of the vaccine in prophylactic xenograft tumor model was evaluate by observing tumor volumes with a caliper and tumor growth with MRI.Results Both SpyCatcher-mi3 and OVA257-264-mi3 could be self-assembled to form homogeneous and stable nanoparticles,with an average particle size of about 43.8 and 91.3 nm,respectively.The OVA257-264-mi3 was safe for in vitro and in vivo toxicity evaluation.The number of IFN--y secreting cells per 1 × 106 splenic lymphocytes reached 253 in the OVA257-264-mi3 group of mice,significantly higher than that in the OVA257-264 group and the Control group(P＜0.05).The tumor volume of mice in the OVA257-264-mi3 group was about 151.1 mm3 on day 22,which was significantly smaller than that of the OVA257-264 group and the Control group(P＜0.05),and the survival rate during the observation period reached 60％,which was significantly higher than that of the OVA257-264 groups(P＜0.05).Conclusion Nanoparticle vaccine OVA257-264-mi3 is successfully constructed,and it shows enhancing effect on the immunogenicity of the antigen epitope peptide,and exerts protective effect on prophylactic xenograft tumor model,providing a theoretical basis for the research of tumor neoantigen vaccines.

Objective:To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain(CIVP)and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase(MAPK)/Ets-like transcription factor 1(ELK1)signaling pathway in the spinal cord. Methods:Clean-grade male Sprague-Dawley rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion(HPM)group,a sham-HPM group,a p38 MAPK inhibitor group,and a dimethyl sulfoxide(DMSO)group.CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50%ethanol.The HPM group was treated with HPM;the sham-HPM group was treated the same as the HPM group,but the moxa cones were not ignited;rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor(SB203580);rats in the DMSO group received L5-L6 intrathecal injection of 2%DMSO.Abdominal withdrawal reflex(AWR),mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were used to observe pain-related behaviors in each group.Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue.Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1(ASK1),MAPK kinase(MKK)3/6,p38 MAPK,ELK1,and mitogen and stress-activated protein kinase 1(MSK1)in the spinal cord. Results:Compared with the normal group,CIVP rats had severe colonic inflammatory injuries,and the pathological injury scores increased significantly,along with increased AWR scores under different colorectal distension(CRD)stimulation pressures and decreased MWT and TWL;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,MSK1,ASK1,MKK3,and MKK6 all increased in the spinal cord(P<0.01).After HPM treatment,the colon injuries were repaired,and the pathological injury scores decreased;under different CRD stimulation pressures,the AWR scores decreased,and the MWT and TWL increased;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,ASK1,and MKK3 in the spinal cord also decreased,with statistically significant differences compared with the model group and the sham-HPM group(P<0.01).There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group(P>0.05),and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion:HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1,MKK3,p38 MAPK,and ELK1 in the spinal cord of CIVP rats.The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Objective:To explore and compare the image quality and radiation dose between the spiral scanning and the axial scanning for skull phantom based on specific conditions.Methods:The position of the orbitomeatal base line(OBL)of the skull phantom was marked,and the different angles of elevation of skull were adjusted.The angles between OBL and bed surface were respectively set as 90°,100°,110° and 120°.The axial scanning and spiral scanning were respective adopted to conduct 24 times of image acquisition when the computed tomography dose index(CTDIvol)of fixed volume were respectively 40,50 and 60 mGy.The cross section of axial scanning was vertical to OBL,and the images of spiral scanning used the reconstructed technique of image quality enhancement(IQE)of removing spiral artifacts to conduct reconstruction along the OBL direction.The CT value(HU)and standard deviation(SD)of the bilateral cerebellum,temporal lobe,frontal lobe and parietal lobe of the phantom were measured,and the signal-to-noise ratio(SNR)of each lobe of the phantom was calculated.The CTDIvol and dose-length product(DLP)were recorded,and the effective dose(ED)of lens was calculated.Results:The differences of the SNR values of cerebellum and occipital lobe(R),cerebellum and occipital lobe(L),temporal lobe(R),temporal lobe(L),frontal lobe(R),frontal lobe(L),parietal lobe(R)and parietal lobe(L)between two kinds of scanning models were significant(F=6.48,5.83,7.00,6.20,7.30,8.26,5.72,5.83,P<0.05),respectively.There was significant difference in lens DLP between the two kinds of scanning models(F=10.96,P<0.05).The spiral scanning and IQE reconstructed technique were used to conduct image acquisition and processing.The SNR value of spiral scanning imaging was better than that of axial scanning,and the reconstructions of coronal and sagittal positions could be conducted,and the radiation doses of lens were similar,but the DLP value of spiral scanning was slightly higher than that of axial scanning at the same CTDIvol.Conclusion:Using the IQE reconstruction technique of spiral scanning can obtain satisfactory CT sectional images of skull under the situations that machine cannot change scanning angle or the scanning of axial position is unable to conduct cooperation.

Objective:To analyze the expression level of hepcidin in urine of patients with type 2 diabetic kidney disease (DKD) in different stages and its relationship with DKD and related indicators.Methods:From June 2022 to December 2023, 139 inpatients with type 2 diabetes mellitus in the Department of Endocrinology, Zhoupu Hospital Affiliated to Shanghai Health Medical College were selected as the research objects. The stage of DKD was judged by urinary albumin/creatinine ratio (UACR): UACR <30 mg/g in stage A1, UACR ≥30 mg/g~≤300 mg/g in stage A2. DKD in stage A3 was UACR >300 mg/g. According to the stage of DKD, there were 50 patients with stage A1 (group A1), 47 patients with stage A2 (group A2), and 42 patients with stage A3 (group A3). Urinary hepcidin was determined by enzyme-linked immunosorbent assay, and fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase (ALT), serum creatinine and hemoglobin A1c (HbA1c) were measured and compared. The correlation between urinary hepcidin and other markers, the risk factors of DKD and the evaluation of diagnostic value were analyzed. Measurement data with normal distribution were expressed as xˉ± s, mean comparison among the three groups, if the variance was homogeneous, the analysis of variance test was used; if the variance was not homogeneous, the Welch test was used; the proportion or rate of enumeration data among the groups was tested by χ2 test; Pearson correlation analysis was used for correlation analysis; binary Logistic regression model was used for multivariate analysis; The value of urinary hepcidin in the diagnosis of DKD was analyzed by receiver operating characteristic curve. Results:Urinary hepcidin was (5.3±1.0) μg/L in group A1, (7.7±2.5) μg/L in group A2, and (10.1±2.7) μg/L in group A3. There was significant difference among the three groups ( F=58.92， P<0.001), and urinary hepcidin increased with the severity of DKD; Urinary Hepcidin was related to UACR ( R=0.684, P<0.001), serum creatinine ( R=0.590, P<0.001), course of disease ( R=0.485, P<0.001), triglyceride ( R=0.264, P=0.002), age ( R=0.235, P<0.001), P=0.005), total cholesterol ( R=0.224, P=0.008), systolic pressure ( R=0.194, P=0.022), glomerular filtration rate ( R=-0.540, P<0.001) and BMI ( R=-0.175, P=0.040); There was no correlation with fasting blood glucose, HbA1c, ALT and diastolic blood pressure (all P>0.05). Secondly, the increase of urinary hepcidin level was a risk factor for DKD by binary Logistic regression analysis ( OR=4.147,95% CI: 2.154-7.984, P<0.001). Finally, receiver operating characteristic curve analysis showed that the optimal cut-off point of urinary hepcidin was 6.35 μg/L, with a sensitivity of 0.831 and a specificity of 0.880. Conclusion:Urinary hepcidin increases with the severity of DKD, which may be a biomarker for early diagnosis of DKD.

Objective To investigate the effect of malignant cerebellar hemorrhage on 3-month prognosis of small spontaneous cerebellar hemorrhage.Methods Clinical data of 380 consecutive patients with spontaneous cerebellar hemorrhage admitted in Emergency Department of the Affil-iated Hospital of Guizhou Medical University,Neurosurgery Department of Jinyang Hospital Af-filiated to Guizhou Medical University,and Neurosurgery Department of the Second Affiliated Hospital of Guizhou Medical University from April 2014 to March 2023 were collected and retro-spectively analyzed,and finally,70 patients who met the requirements of small amount of sponta-neous cerebellar hemorrhage were enrolled in this study.They were assigned into benign cerebel-lar hemorrhage group(43 cases)and malignant cerebellar hemorrhage group(27 cases).Accord-ing to their clinical outcomes in 3 months after onset,they were divided into a good prognosis group(51 cases)and a poor prognosis group(19 cases).General clinical data,imaging data,com-plications,inflammatory indicators and prognosis were collected.After collinear diagnosis was used to exclude factors with collinear influence,the independent correlation between good progno-sis and poor prognosis was analyzed by binary logistic regression model.Finally,ROC curve was plotted to analyze the significant data.Results The maximum diameter of hematoma was signifi-cantly larger in the malignant cerebellar hemorrhage group than the benign group(P=0.021).The patients of the poor prognosis group had larger proportion of malignant cerebellar hemor-rhage,and higher neutrophil percentage,WBC count and NLR than those of the good prognosis group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that malignant cere-bellar hemorrhage was an independent predictor of poor prognosis in 3 months(OR=6.218,95％CI:1.140-17.623,P=0.013).The sensitivity,specificity,positive predictive value,negative pre-dictive value and Youden index of malignant cerebellar hemorrhage in predicting the 3-month prognosis of patients were 63.2％,70.6％,44.4％,83.7％and 0.338,respectively,and the AUC value was 0.669.Conclusion Malignant cerebellar hemorrhage is an independent predictor of 3-month prognosis in patients with small spontaneous cerebellar hemorrhage.The patients with malignant cerebellar hemorrhage have poor prognosis than those with benign cerebellar hemorrhage.

By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.