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.

Objective:To investigate the efficacy and safety of tirofiban versus argatroban in the treatment of acute ischemic stroke. Methods:This study was a retrospective cohort study. Sixty-eight patients with acute ischemic stroke who were continuously admitted to Department of Neurology of The Third People's Hospital of Hubei Province from August 2022 to September 2023 were divided into tirofiban group ( n = 33) and argatroban group ( n = 35) according to the treatment regimen. Both groups were treated according to their respective treatment protocols for 7 days. Clinical outcomes were assessed based on the modified Rankin Scale (mRS) scores. The excellent clinical outcome (mRS score 0-1 points), good clinical outcome (mRS score 0-2 points), symptomatic intracranial hemorrhage, and mortality rates were compared between the two groups at 90 days post-treatment. Results:In the tirofiban group, the proportion of excellent clinical outcomes was 30.3% (10/33), which was significantly lower than the 65.7% (23/35) in the argatroban group (χ2 = 8.53, P = 0.003). However, the difference in the proportion of good clinical outcomes between the two groups was not statistically significant [54.5% (18/33) vs. 74.3% (26/35), χ2 = 2.90, P = 0.089]. There were no statistically significant differences between the two groups regarding symptomatic intracranial hemorrhage and mortality rates (both P > 0.05). Conclusion:For patients with acute ischemic stroke, the use of tirofiban or argatroban is effective and safe. Patients treated with argatroban are more likely to achieve excellent clinical outcomes; however, larger randomized controlled trials are needed for further confirmation.

Objective:To investigate the prevalence and risk factors of stroke in residents of Hanzhong community, Wuhan city, Hubei province, and develop subsequent prevention and treatment measures.Methods:A questionnaire survey, physical examination, and laboratory tests were conducted from May 1 to July 31, 2023, among a population of 801 residents aged 40 years and older in Hanzhong community, Wuhan city, Hubei province, using multi-stage whole cluster random sampling.Results:Among the 801 residents surveyed, 28 were found to have suffered from stroke, yielding a prevalence rate of 3.5%. Additionally, there were 255 individuals identified as high-risk, accounting for 31.8% of the population. The risk factors for stroke, ranked from highest to lowest in prevalence, were as follows: hypertension (24.3%), dyslipidemia (23.6%), lack of exercise (17.6%), smoking (13.1%), diabetes (12.0%), family history of stroke (9.0%), obesity or overweight (8.6%), and atrial fibrillation or valvular heart disease (3.0%). The prevalence of stroke is higher in men than in women, and it continues to increase with advancing age (χ 2 = 33.95, P < 0.001). Homocysteine is likely to contribute to the occurrence of stroke through its association with hypertension (χ2 = 42.63, P < 0.001). Additionally, homocysteine levels have emerged as another significant risk factor for stroke among individuals who are at high risk (χ2 = 5.74, P < 0.05). Conclusion:In Hanzhong community, Wuhan city, Hubei province, smoking, hypertension, overweight, and obesity are the major risk factors for stroke among residents aged 40 years and older. Homocysteinemia is closely related to these high-risk factors for stroke. Therefore, screening and prevention of elevated homocysteine levels will be one of the critical indicators for the subsequent screening and prevention of stroke.

Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Objective: To investigate the prevalence of diabetes among individuals at high risk of diabetes in Baoshan District, Shanghai Municipality, so as to provide insights into community-based diabetes management. Methods: Permanent residents at ages of 35 years and older were sampled from Baoshan District using a multistage stratified cluster sampling method, and residents at a high risk of diabetes were screened using the Form for Risk Assessment of Diabetes among Community Residents in Shanghai Municipality. Participants' demographics, disease history and history of medication were collected using questionnaire surveys, and height, body weight, waist circumference, hip circumference, and blood pressure were measured. Diabetes was screened using fasting blood glucose and glucose tolerance test. The factors affecting the development of diabetes were identified among high-risk residents for diabetes using a multivariable logistic regression model. Results: A total of 3 107 residents at a high risk for diabetes were enrolled, including 1 165 men (37.50%) and 1 942 women (62.50%) with a mean age of (63.58±9.77) years. The prevalence of diabetes was 21.69% among the study subjects, and multivariable logistic regression analysis showed that men (OR=1.689, 95%CI: 1.357-2.104), age (40 years-, OR=4.833, 95%CI: 1.036-22.553; 50 years-, OR=2.627, 95%CI: 1.432-4.819; 60 years-, OR=1.551, 95%CI: 1.119-2.150; 70 years and older, OR=1.579, 95%CI: 1.232-2.025); high school/technical secondary school (OR=2.677, 95%CI: 1.636-4.380), overweight/obesity (OR=1.891, 95%CI: 1.447-2.472), hypertension (OR=1.306, 95%CI: 1.049-1.626), dyslipidemia (OR=1.428, 95%CI: 1.114-1.831), history of impaired glucose regulation (OR=15.161, 95%CI: 11.827-19.434) and family history of type 2 diabetes mellitus (OR=2.092, 95%CI: 1.619-2.704) caused an increased risk of diabetes among residents at a high risk diabetes. Conclusions The prevalence of diabetes was 21.69% among high-risk populations of diabetes in Baoshan District. Gender, age, educational level, overweight/obesity, hypertension, dyslipidemia, history of impaired glucose regulation and family history of type 2 diabetes mellitus are factors affecting the development of diabetes among high-risk populations.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Objective::Fish oil (FO) contains omega-3 that inhibits inflammation and blood lipid metabolism, giving it a protective cardiovascular effect. Due to dietary habits, a majority of large-scale clinical trials examining FO and cardiovascular health have been conducted in the Caucasian populations. However, the effects of FO on cardiovascular inflammation indicators and blood lipid metabolism in the Chinese population remain unclear. This study aimed to perform a meta-analysis to elucidate the impact of FO on cardiovascular health in the Chinese population.Methods::Web searches were utilized to locate records of clinical trials related to cardiovascular health and consumption of FO capsules or fish containing omega-3 in several databases, including PubMed, Medline, Embase, Cochrane Library, CNKI, and ClinicalTrial.gov, etc. We obtained lipid metabolism and related proinflammatory markers as the study outcome. We used Review Manager 5.4 and Stata 16 for the statistical analysis. If the I2 ≥ 30%, a random effects model was used, and if the I2 < 30%, a fixed effects model was used. Results::Twenty eligible trials were shortlisted from >1000 records. The meta-analysis revealed that supplementation with eicosapentaenoic acid and docosahexaenoic acid reduced systolic blood pressure by 1.88 mmHg (95% CI: -4.97 to -1.20, P = 0.23), diastolic blood pressure by 0.86 mmHg (95% CI: -1.79 to 0.06, P = 0.07), fasting blood glucose by 0.05 mmol/L (95% CI: -0.16 to 0.06, P = 0.40), and low-density lipoprotein-cholesterol by 0.12 mmol/L (95% CI: -0.23 to -0.01, P = 0.04), when compared to placebo. However, these supplements increased high-density lipoprotein-cholesterol by 0.03 mmol/L (95% CI: 0.01 to 0.05, P < 0.001), when compared to placebo. Dose subgroup analyses examining total cholesterol found that the low-dose group (mean difference = -0.44, 95% CI: -0.55 to -0.34, P < 0.001) demonstrated the best results. Further, results from dose subgroup analyses showed that the all-dose group demonstrated a decrease in tumor necrosis factor (TNF-α) levels among the study subjects, when compared to other groups. Conclusions::Consumption of FO containing omega-3 fatty acids in the Chinese population can improve lipid metabolism and reduce levels of proinflammatory markers. Therefore, it is necessary to vigorously promote the benefits of consuming FO to prevent cardiovascular diseases throughout China.

Objective::Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure (HF). Growth differentiation factor 15 (GDF15) dramatically increases during cardiac hypertrophy and dysfunction, but its functions and mechanisms are barely known. This study aims to elucidate the role and mechanism of GDF15 in HF.Methods::Between January 2017 and August 2018, 57 patients diagnosed with chronic HF (aged >18 years, with left ventricular ejection fraction (LVEF) ≤35%) and 57 non-HF patients (aged >18 years, LVEF >35%) were prospectively enrolled in this study based on the balance of the baseline characteristics. Other acute or chronic diseases and pregnant/lactating women were excluded. The serum concentrations of GDF15 were detected. Isoproterenol (ISO)-induced HF mouse model was established by pumping with ISO (30 mg/(kg·day)) for 4 weeks, and the GDF15 expression in serum and heart tissue was evaluated in vivo. Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage. The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro.Results::After adjusting the baseline characteristic, serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients. Similarly, in the ISO-induced HF mouse model, the significant increase in GDF15 was associated with the process of HF in vivo. Moreover, the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model. Furthermore, using primary cardiomyocytes, we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model. Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress. In contrast, the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage. Conclusions::GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF. These findings indicate that GDF15 may be a potential therapeutic target for HF.

Objective::Fish oil (FO) contains omega-3 that inhibits inflammation and blood lipid metabolism, giving it a protective cardiovascular effect. Due to dietary habits, a majority of large-scale clinical trials examining FO and cardiovascular health have been conducted in the Caucasian populations. However, the effects of FO on cardiovascular inflammation indicators and blood lipid metabolism in the Chinese population remain unclear. This study aimed to perform a meta-analysis to elucidate the impact of FO on cardiovascular health in the Chinese population.Methods::Web searches were utilized to locate records of clinical trials related to cardiovascular health and consumption of FO capsules or fish containing omega-3 in several databases, including PubMed, Medline, Embase, Cochrane Library, CNKI, and ClinicalTrial.gov, etc. We obtained lipid metabolism and related proinflammatory markers as the study outcome. We used Review Manager 5.4 and Stata 16 for the statistical analysis. If the I2 ≥ 30%, a random effects model was used, and if the I2 < 30%, a fixed effects model was used. Results::Twenty eligible trials were shortlisted from >1000 records. The meta-analysis revealed that supplementation with eicosapentaenoic acid and docosahexaenoic acid reduced systolic blood pressure by 1.88 mmHg (95% CI: -4.97 to -1.20, P = 0.23), diastolic blood pressure by 0.86 mmHg (95% CI: -1.79 to 0.06, P = 0.07), fasting blood glucose by 0.05 mmol/L (95% CI: -0.16 to 0.06, P = 0.40), and low-density lipoprotein-cholesterol by 0.12 mmol/L (95% CI: -0.23 to -0.01, P = 0.04), when compared to placebo. However, these supplements increased high-density lipoprotein-cholesterol by 0.03 mmol/L (95% CI: 0.01 to 0.05, P < 0.001), when compared to placebo. Dose subgroup analyses examining total cholesterol found that the low-dose group (mean difference = -0.44, 95% CI: -0.55 to -0.34, P < 0.001) demonstrated the best results. Further, results from dose subgroup analyses showed that the all-dose group demonstrated a decrease in tumor necrosis factor (TNF-α) levels among the study subjects, when compared to other groups. Conclusions::Consumption of FO containing omega-3 fatty acids in the Chinese population can improve lipid metabolism and reduce levels of proinflammatory markers. Therefore, it is necessary to vigorously promote the benefits of consuming FO to prevent cardiovascular diseases throughout China.

Objective::Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure (HF). Growth differentiation factor 15 (GDF15) dramatically increases during cardiac hypertrophy and dysfunction, but its functions and mechanisms are barely known. This study aims to elucidate the role and mechanism of GDF15 in HF.Methods::Between January 2017 and August 2018, 57 patients diagnosed with chronic HF (aged >18 years, with left ventricular ejection fraction (LVEF) ≤35%) and 57 non-HF patients (aged >18 years, LVEF >35%) were prospectively enrolled in this study based on the balance of the baseline characteristics. Other acute or chronic diseases and pregnant/lactating women were excluded. The serum concentrations of GDF15 were detected. Isoproterenol (ISO)-induced HF mouse model was established by pumping with ISO (30 mg/(kg·day)) for 4 weeks, and the GDF15 expression in serum and heart tissue was evaluated in vivo. Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage. The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro.Results::After adjusting the baseline characteristic, serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients. Similarly, in the ISO-induced HF mouse model, the significant increase in GDF15 was associated with the process of HF in vivo. Moreover, the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model. Furthermore, using primary cardiomyocytes, we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model. Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress. In contrast, the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage. Conclusions::GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF. These findings indicate that GDF15 may be a potential therapeutic target for HF.