Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

A family carrying a homozygous variant of DNAJB2 gene C.91C>T (p.His31Tyr) with distal hereditary motor neuropathy (dHMN) associated with early-onset Parkinson′s disease was reported. The patient presented with distal limb weakness and atrophy at the early stage of the disease, and developed Parkinson′s symptoms more than 10 years later. Neuroelectrophysiological examination suggested motor and sensory axonal involvement. This mutation site had not been reported and was considered to be a neogenic mutagenicity of dHMN, excluding other mutations that can cause early-onset Parkinson′s disease.

Objective:To explore the correlation between myocardial damage and vascular endothelial growth factor (VEGF), red blood cell distribution width (RDW), and myocardial enzyme spectrum in children with severe mycoplasma pneumoniae pneumonia.Methods:Sixty children with severe mycoplasma pneumoniae pneumonia and myocardial damage admitted to Jining Medical University from January 2019 to December 2020 were selected as the observation group, and 60 children with severe mycoplasma pneumoniae pneumonia admitted during the same period were selected as the control group. The differences in clinical data and imaging features between the two groups were compared. Pearson correlation analysis was used for correlation analysis; The logistic regression method was applied to analyze the influencing factors of myocardial damage in children with severe mycoplasma pneumoniae pneumonia. The value of VEGF and RDW in predicting myocardial damage in children with severe mycoplasma pneumoniae pneumonia was analyzed using receiver operating characteristic (ROC) curves.Results:The levels of C-reactive protein (CRP), procalcitonin (PCT), VEGF, RDW, creatine kinase isoenzyme (CK-MB), creatine kinase (CK), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH) in the observation group were significantly higher than those in the control group (all P<0.05), and the duration of fever, application of macrolide drugs, and glucocorticoid application time were significantly longer than those in the control group (all P<0.05). There was no statistically significant difference in pulmonary imaging characteristics between the observation group and the control group (all P>0.05). The VEGF and RDW in the observation group were positively correlated with CK-MB and cTnI (all P<0.05). Logistic regression analysis showed that duration of fever, VEGF, RDW, and duration of macrolide drug use were the influencing factors for myocardial damage in children with severe mycoplasma pneumoniae pneumonia (all P<0.05). The area under the ROC curve of VEGF combined with RDW in predicting myocardial damage in children with severe mycoplasma pneumoniae pneumonia was 0.899, significantly higher than that predicted by VEGF and RDW alone (all P<0.05). Conclusions:The serum VEGF and RDW levels in children with severe mycoplasma pneumoniae pneumonia accompanied by myocardial damage are elevated and positively correlated with myocardial enzyme spectrum indicators, which has certain application value in predicting myocardial damage.

Since the outbreak of corona virus disease 2019 (COVID-19), viral strains have mutated and evolved. Vaccine research is the most direct and effective way to control COVID-19. According to different production mechanisms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines included inactivated virus vaccine, live attenuated vaccine, mRNA vaccine, DNA vaccine, viral vector vaccine, virus-like particle vaccine and protein subunit vaccine. Among them, viral protein subunit vaccine has a wide application prospect due to its high safety and effectiveness. Viral nucleocapsid protein has high immunogenicity and low variability which could be a new direction for vaccine production. We summarized the current development of vaccine research by reviewing the current progress, vaccine safety and vaccine immune efficiency. It is hoped that the proposed possible development strategies could provide a reference for epidemic prevention work in future.
Humans ; SARS-CoV-2/genetics* ; COVID-19/prevention & control* ; Protein Subunits ; Vaccines, DNA ; Nucleocapsid Proteins

Neurexin-3α, discovered in 2016, is a new type of autoimmune encephalitis antibody. Anti-neurexin-3α antibody-associated encephalitis is generally associated with prodromal symptoms or mood changes, having main clinical manifestations as seizures, memory disorders, confusion or loss of consciousness, central ventilation insufficiency, abnormal behavior, and speech disorders. This paper reviews the relevant research progress at home and abroad about pathogenesis, diagnosis and differential diagnosis, treatment and prognosis of anti-neurexin-3α antibody-associated encephalitis, so as to expand the understanding of clinicians for this disease.

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

The brain is an important organ in the human body with high metabolic requirements, and epilepsy, as a common neurological disease, also exhibits high metabolic characteristics in its lesion area. At present, controlling seizures caused by drug-resistant epilepsy or specific metabolic defects through metabolic regulation has shown good anti epileptic effects. In recent years, people have become increasingly interested in the relationship between brain metabolism and epileptic seizures. So far, several new anti epileptic therapies targeting metabolic pathways have been proposed, including inhibition of glycolysis, targeted lactate dehydrogenase, and dietary therapy. It is highly promising to intervene in epilepsy by regulating brain metabolism, but currently we still lack a thorough understanding of the role of brain metabolism in controlling epilepsy. This review aims to gain a deeper understanding of energy metabolism in the brain and its correlation with epilepsy, emphasizing the regulation of neuronal excitability through glycolysis, in order to search for effective anti epileptic therapies, in order to better understand the role of glycolysis in epileptic seizures and reveal potential therapeutic targets for epilepsy.

Resilience as a hot topic concept is mostly used in psychological research, and physical resilience is an emerging concept relevant to successful aging.Definitions of physical resilience are varied and uncertain, and there is no unified quantification method for it.Also, there is no consensus on the definition of phenotypes related to physical resilience.Further research into the exact concept of physical resilience may help achieve healthy aging.In this paper, we will review the definition of physical resilience, quantification methods of influencing factors, and various related phenotypes.

Objective:To establish a hydride generation atomic fluorescence method using ammonium persulfate as the digestion reagent for determination of arsenic in urine (hereinafter referred to as this method).Methods:The collected urine samples with ammonium persulfate were heated and digested on the tubular electric heating automatic control constant temperature digester (60 holes), with 5% hydrochloric acid solution as reaction medium and current carrier and 1.5% potassium borohydride solution as reducing agent. Arsenic content was determined with a four-channel atomic fluorescence spectrometer. The arsenic standard solution of 0 - 10 μg/L was prepared to determine the standard curve of this method, and the method was evaluated from the detection limit, linear range, correlation coefficient, precision, standard addition recovery experiment, and urine arsenic quality control sample detection. The standard method "Determination of Arsenic in Urine by Hydride Generation Atomic Fluorescence Spectrometry" (WS/T 474-2015, referred to as the standard method) was used for comparison experiments.Results:When the sampling volume was 1 ml, the detection limit of this method (digest with 1 ml 1.5 mol/L ammonium persulfate) was 0.03 μg/L. In the range of arsenic content from 0 - 10 μg/L, the linear relationship between arsenic content and fluorescence intensity was good, and the correlation coefficients ( r) were all 0.999 9. The relative standard deviations( RSD) of the three replicates of urine samples with different concentrations were 1.00%, 0.89% and 0.49%, respectively. Urine arsenic quality control samples were tested, and the test results were all within the range of public values; the overall average recovery was 102.29%, and the recovery range was 92.10% - 108.15%. Compared with the standard method in the determination results of 20 urine samples, the difference was not statistically significant ( t = - 0.40, P > 0.05). Conclusions:The hydride generation atomic fluorescence spectrometry using ammonium persulfate as digestion reagent for the determination of arsenic in urine has the advantages of low detection limit, good precision, high accuracy, small amount of sampling and digestion reagent, simple operation, and less harmful gas generation in sample pretreatment. It is suitable for rapid determination of arsenic in urine in large quantities.