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Background The triglyceride–glucose (TyG) index, which is a reliable surrogate marker of insulin resistance (IR), has been associated with cardiovascular diseases. However, evidence of the impact of the TyG index on the severity of coronary artery disease (CAD) is limited. This study investigated the relationship between the TyG index and CAD severity of individuals with different glucose metabolic statuses. Methods This study enrolled 2792 participants with CAD in China between January 1, 2018 and December 31, 2021. All participants were divided into groups according to the tertiles of the TyG index as follows: T1 group, TyG index < 6.87; T2 group, TyG index ≥ 6.87 to < 7.38; and T3 group, TyG index ≥ 7.38. The glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus (pre-DM), and diabetes mellitus according to the standards of the American Diabetes Association. CAD severity was determined by the number of stenotic vessels (single-vessel CAD versus multi-vessel CAD). Results We observed a significant relationship between the TyG index and incidence of multi-vessel CAD. After adjusting for sex, age, body mass index, smoking habits, alcohol consumption, hypertension, estimated glomerular filtration rate, antiplatelet drug use, antilipidemic drug use, and antihypertensive drug use in the logistic regression model, the TyG index was still an independent risk factor for multi-vessel CAD. Additionally, the highest tertile of the TyG group (T3 group) was correlated with a 1.496-fold risk of multi-vessel CAD compared with the lowest tertile of the TyG group (T1 group) (odds ratio [OR], 1.496; 95% confidence interval [CI], 1.183–1.893; P < 0.001) in the multivariable logistic regression model. Furthermore, a dose–response relationship was observed between the TyG index and CAD severity (non-linear P = 0.314). In the subgroup analysis of different glucose metabolic statuses, the T3 group (OR, 1.541; 95% CI 1.013–2.344; P = 0.043) were associated with a significantly higher risk of multi-vessel CAD in individuals with pre-DM. Conclusions An increased TyG index was associated with a higher risk of multi-vessel CAD. Our study indicated that TyG as an estimation index for evaluating IR could be a valuable predictor of CAD severity, especially for individuals with pre-DM.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 (COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial ( NCT04892459 ). Adults who had received two doses of CoronaVac in the past 3–6 months were vaccinated with Convidecia ( n  = 96) or CoronaVac ( n  = 102). Adults who had received one dose of CoronaVac in the past 1–3 months were also vaccinated with Convidecia ( n  = 51) or CoronaVac ( n  = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting. Heterologous vaccination with Convidecia, a recombinant adenovirus type 5-vectored COVID-19 vaccine, after one or two doses of CoronaVac, an inactivated SARS-CoV-2 vaccine, is more reactogenic but elicits significantly higher levels of neutralizing antibodies than homologous vaccination.

Long short-term memory (LSTM) networks are widely used in biomechanical data analysis but have the significant limitations in interpretability and decision transparency. Combining graph neural networks (GNN) with gate recurrent units (GRU) may offer a better solution. This study proposes and validates a hybrid GNN-GRU model for predicting baseball pitching speed and enhancing its interpretability using layer-wise relevance propagation (LRP). C3D data from 53 baseball athletes were downloaded from a public dataset. Kinematic features of 9 joints and pitching speed during the pitching process were calculated using Visual3D, resulting in a total of 208 valid pitches. The feature data were input into both LSTM and GNN-GRU hybrid models, with hyperparameters tuned using particle swarm optimization. LRP was employed to obtain the contribution rate changes of kinematic features to the prediction results throughout the pitching cycle. The prediction accuracy of the models was evaluated using mean absolute error (MAE), mean squared error (MSE), and R-squared (R 2 ). The results showed that there were the significant statistical differences in the MAE and R 2 metrics between the LSTM model and the GNN-GRU model in predicting pitching speed on the test set. The MAE ( P  = 0.000, Z = − 5.170, Cohen’s d  = 1.514) and R 2 ( P  = 0.000, Z = − 2.981, Cohen’s d  = 2.314) of the LSTM model were significantly lower than those of the GNN-GRU model. Compared to LSTM, the GNN-GRU model achieved better prediction accuracy but was potentially more susceptible to the influence of data variability. Moreover, the GNN-GRU-based model demonstrated the better interpretability and decision transparency.

Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data. Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines. Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101.

Background Edaravone dexborneol and dl-3-n-butylphthalide are two innovative brain cytoprotective drugs from China that have been approved and widely prescribed for acute ischemic stroke, and the cost of the two drugs are partially paid by the Chinese medical insurance system. This study aimed to investigate and compare the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke from the Chinese healthcare system’s perspective. Methods A model combining a short-term decision tree model with 90 days and a long-term Markov model with a life-time horizon (40 years) was developed to simulate the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke over a lifetime horizon. Since the absence of a head-to-head clinical comparison of two therapies, an unanchored matching-adjusted indirect comparison (MAIC) was conducted by adjusting the patient characteristics using individual patient data from pivotal phase III trial of edaravone dexborneol and published aggregated data of dl-3-n-butylphthalide. Health outcomes were measured in quality-adjusted life years (QALYs). Utilities and costs (Chinese Yuan, CNY) were derived from publications and open-access database. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of results. Results Compared with patients in dl-3-n-butylphthalide arm, edaravone dexborneol arm was found to be cost-effective in 90 days and highly cost-effective as the study horizons extended. With a similar direct medical cost, patients in edaravone dexborneol arm slightly gained an additional 0.1615 QALYs in life-time. In the long term (40 years), patients in edaravone dexborneol arm and dl-3-n-butylphthalide arm yielded 8.0351 and 7.8736 QALYs with the overall direct medical cost of CNY 29,185.23 and CNY 29,940.28, respectively. The one-way sensitivity analysis suggested that the incremental cost-effectiveness ratio was most sensitive to the price of edaravone dexborneol and dl-3-n-butylphthalide. Conclusion Edaravone dexborneol is a cost-effective alternative compared with dl-3-n-butylphthalide for acute ischemic stroke patients in current medical setting of China.

This study examines global trends in cardiovascular disease (CVD) associated with kidney dysfunction (KD) from 1990 to 2021 and projects future trends through 2050. This study analyzed the 2021 Global Burden of Disease (GBD) database, focusing on age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years rate (ASDR), absolute numbers, estimated annual percentage change, and average annual percent change. A Bayesian age-period-cohort model was employed to project global trends from 2022 to 2050. Variables included age, gender, national levels, and Socio-demographic Index (SDI) regions. From 1990 to 2021, the CVD burden from KD increased, with deaths rising from 1,312,393 to 2,095,800 and DALYs from 27,382,767 to 41,589,861. However, the ASMR decreased from 40.58 per 100,000 in 1990 to 25.55 in 2021, while ASDR fell from 742.17 to 489.81 during the same period. The burden was higher in men, peaking at ages 70-74 and in women at ages 85-89. Regions with lower-middle and low SDI recorded the highest CVD burden, inversely related to SDI levels. Geographically, Central Asia and Eastern Europe recorded the highest rates, while high-income Asia Pacific and Southern Latin America had the lowest. Projections suggest a sustained decline in global CVD burden due to KD from 2022 to 2050, although disparities between sexes are expected to persist, with men bearing a heavier burden. CVD attributable to KD remains a major global public health challenge, especially for men, the elderly, and low SDI regions. These spatial and temporal variations highlight the need for region-specific healthcare strategies.

Background Drug shortages significantly threaten public health and medical service provision worldwide. Research evidence on the complete picture of drug shortages is currently scant in China. This study aimed to provide a descriptive overview and a reference for alleviating of drug shortages in China. Methods National and provincial lists of drug shortages issued in China from 2018 to 2021 were collected and summarized. The information on essential medicines, medical insurance drugs, emergency drugs, and volume-based purchasing drugs was then matched with a drug shortage list to analyse the characteristics, proportion and incidence of drug shortage on each list based on the analysis of information such as dosage form, shortage frequency, and Anatomical Therapeutic Chemical (ATC) classification of the drugs in shortage. Results A total of 24 provinces issued drug shortages lists involving 408 drugs from 2018 to 2021. All 58 drugs in the national drug list were included on the provincial drug shortage list. Among all the drugs in shortage, the most significant shortage involved injections, accounting for 45.3% (185/408). Ninety-five drugs (23.3%) were in shortage 5 times (annual shortage > 1 time) or more in the provincial lists, and 199 drugs (48.8%) were on the shortage list only once. In terms of therapeutic property, nearly all categories of drugs had been reported in shortage, among which cardiovascular drugs, nervous system drugs, anti-tumor and immunomodulatory drugs, and blood and hematopoietic organ drugs accounted for more than 10%. There is no significant difference in drug shortage among economic regions. Comparing drugs in shortage and various lists, 81.9% (334/408), 51.0% (208/408) and 67.9% (277/408) fell on the National Medical Insurance Drug List, National Essential Medicines List, and WHO Model List of Essential Medicines, respectively, while the volume-based purchasing drugs accounted for 3.4% (14 drugs). The incidence of drug shortages on NEML, WHO Model List of Essential Medicines and medical insurance category A was significantly higher than that of medical insurance category B and volume-based purchasing drugs (P < 0.05). Of the Emergency Drugs List, 72.0% (36/50) also experienced shortages, significantly higher than all the above categories (P < 0.05). Conclusions In China, drug shortages were severe and complicated. Drug shortages vary among economic regions but are not significant. In comparison, the national procurement pattern of volume-based drug purchasing may be conducive to alleviating the drug shortage problem. Collaboration of all partners was recommended to ensure the supply of clinically necessary drugs.

This longitudinal cohort study aimed to evaluate the associations of proton pump inhibitor (PPI) use and estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) risk, all-cause mortality, and cardiovascular mortality. We analysed data from 30,362 National Health and Nutrition Examination Survey participants (mean age: 49.3 ± 17.6 years; 51.1% women) between 2003 and 2018. Participants were categorised into eight subgroups based on PPI use and eGFR categories. CVD risk was assessed using survey-weighted multivariable logistic regression, while mortality was evaluated with Cox proportional hazards models over a median follow-up of 91 months. Analyses were adjusted for numerous potential confounders, with sensitivity analyses validating the results. Compared to nonusers with normal eGFR, PPI users with eGFR < 30 had the highest odds ratio (OR = 9.29, 95% CI: 3.34-25.81,  < 0.001). Furthermore, in a longitudinal follow-up of 30,329 participants, PPI users with eGFR < 30 exhibited the highest hazard ratio for all-cause mortality (HR = 2.75, 95% CI: 1.42-5.44,  = 0.003). For cardiovascular mortality, elevated risk was identified in PPI users with an eGFR < 60 (HR = 2.80, 95% CI: 1.77-4.41,  < 0.001), and this association remained robust using Fine-Gray competing risk models. This study reveals a strong, graded association between PPI use, reduced eGFR, and an increased risk of CVD, all-cause mortality, and cardiovascular mortality. We recommend integrating eGFR into risk-benefit assessments before initiating PPI therapy.

Objectives Drug-induced thrombocytopenia has been reported for numerous drugs. Vancomycin-induced thrombocytopenia (VIT) is infrequently and often under-recognized. VIT can lead to the serious consequences of some life-threatening bleeding, especially in high-risk population. However, few studies have focused on VIT. This study aimed to describe the occurrence and manifestation of VIT and evaluate its risk factors in real-world settings. Methods A retrospective case-control study of patients treated with intravenous vancomycin was conducted between January 2018 and December 2023. Results Among the 1269 identified patients, the incidence of thrombocytopenia was 3.3% (42/1269) after a medium of 9 days (range, 2 to 22) of the initiation of vancomycin therapy. Twenty-four patients experienced platelet recovery, and all recovered after discontinuing vancomycin, with a mean duration of 9 days (range, 1 to 35) after vancomycin cessation. The severity of thrombocytopenia varied among these patients, with 45.2% (19/42) experiencing Grade 3 to Grade 4 thrombocytopenia. Multivariate analysis indicated that risk factors for VIT were qSOFA score ≥ 2, underlying renal diseases, duration of vancomycin therapy ≥ 8 days, PLT ≤ 150 × 10 9 /L, and BUN ≥ 12 mmol/L. In the retrospective cohort, among patients with 0–5 risk factors, the incidence rates of VIT were 0.2% (1/556), 1.6% (7/439), 5.8% (10/173), 14.9% (11/74), 42.1% (8/19), and 62.5% (5/8) respectively. Conclusion It is crucial for medical staff to remain vigilant and carefully observe any signs of potential bleeding throughout vancomycin therapy, especially in those with more than 3 combined risk factors.

In response to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, over 200 vaccine candidates against coronavirus disease 2019 (COVID-2019) are under development and currently moving forward at an unparalleled speed. The availability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates, which is crucial to control COVID-19 pandemic. Several phase 3 efficacy trials of COVID-19 vaccine candidates are under way, which provide opportunities for the determination of COVID-19 correlates of protection. In this paper, we review current knowledge for existence of COVID-19 correlates of protection, methods for assessment of immune correlates of protection and issues related to COVID-19 correlates of protection.