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.

Objective:To develop a nomogram model utilizing serological indicators for predicting in-hospital major adverse cardiovascular events(MACE)in elderly patients diagnosed with acute coronary syndrome(ACS).Methods:This study involved a retrospective analysis of clinical data from 1, 818 elderly patients with ACS who were treated at the First Medical Center of the General Hospital of the People's Liberation Army from January 2022 to May 2024.The patients were randomly assigned to a training set(1, 272 cases)and a validation set(546 cases)in a 7: 3 ratio.Following a comparison of the two groups, the training set was further categorized into non-MACE and MACE groups based on the occurrence of endpoint events.Univariate analysis, Lasso regression, and multivariate logistic regression analyses were sequentially employed to identify factors influencing in-hospital MACE and to construct the nomogram model.The performance of the model was assessed using receiver operating characteristic(ROC)curves, calibration curves, and decision curves.Results:Among the 1, 818 ACS patients, the mean age was 67 years(interquartile range: 61.0 to 73.0), with 70.4% being male.Almost all indicators(except platelet count)exhibited no statistically significant differences between the training and validation sets(all P>0.05).However, statistically significant differences(all P<0.05)were observed in age, body mass index, neutrophil count, lymphocyte count, monocyte count, white blood cell count, hemoglobin, red blood cell distribution width, mean platelet volume, C-reactive protein(CRP), fibrinogen, D-dimer, albumin, direct bilirubin, troponin T(TnT), fasting blood glucose(FBG), estimated glomerular filtration rate(eGFR), uric acid, N-terminal pro-B-type natriuretic peptide(NT-proBNP), glycated hemoglobin(HbA1c), and high-density lipoprotein cholesterol(HDL-C)between the non-MACE and MACE groups in the training set.Ultimately, seven variables—neutrophil count, hemoglobin, red blood cell distribution width, CRP, TnT, FBG, and NT-proBNP—were selected to construct the nomogram model.The model demonstrated high discrimination in both the training and validation sets, with an area under the curve of 0.86(95% CI: 0.82-0.90)for the training set and 0.85(95% CI: 0.81-0.90)for the validation set.Furthermore, the calibration curves for both cohorts indicated a close agreement between predicted and actual risk estimates, suggesting improved model calibration.Decision curve analysis indicated that the predictive model has notable clinical utility. Conclusions:The constructed nomogram enhances the accuracy of predicting in-hospital MACE in elderly patients with ACS, thereby offering a valuable reference for clinical practice.

Objective To investigate the relationship of TyG index and IC.Methods A cross-sectional study was conducted with 1000 older adults living in Wanshou Road Community from May to December 2023.Finally 820 participants were enrolled,and based on the TyG index,they were divided into lower TyG index group(≤7.349,404 cases)and higher TyG index group(＞7.349,416 cases).After PSM,there were only 522 participants subjected,including 261 individuals in the lower TyG index group 1 (≤7.349)and 416 ones in the higher TyG index group 2(＞7.349).Univariate and multivariate logistic regression analyses were used to assess the correlation between IC and the TyG index as both continuous and categorical variables.PSM was employed to eliminate the confounding effects of covariates to identify the relationship between TyG index and IC in different categories.Results Before PSM,the neutrophil count,WBC count,and Hcy,FPG,TC,TG and HbA1c levels were significantly lower,and lymphocyte count,monocyte count,and AST level were obviously higher in the low TyG index group than the high TyG index group(P＜0.05,P＜0.01).After PSM,the low TyG index group still had notably lower FPG,TG and HbA1c than the high TyG index group(P＜0.05,P＜0.01).ROC curve analysis revealed that the cutoff value of TyG index was 7.349.Taking 7.349 as the cutoff value and TyG index as the cate-gorical variable,multivariate logistic regression analysis displayed that TyG index was correlated with IC[OR=3.921,95％CI:2.800-5.491,P=0.001(Model 1);OR=2.744,95％CI:1.739-4.329,P=0.001(Model 2);OR=2.744,95％CI:1.805-4.171,P=0.001(Model 3);OR=2.722,95％CI:1.530-4.843,P=0.001(after PSM)],indicating that TyG index remains an independent risk factor for IC.Conclusion IC is still correlated with TyG index in community-dwelling elderly individuals under different baseline conditions after adjusting for relevant laboratory indicators.As an indicator generated from routine blood test,TyG index has advantages in terms of cost and time.With further validation,TyG may provide a direction for studying IC prediction.

Objective To investigate the regulatory effects of liraglutide(Lira)on adipocyte brown-ing and its underlying molecular mechanisms.Methods Adipose-derived mesenchymal stem cells were induced to differentiate with palmitic acid(PA)simulating a high-fat environment and lenti-viral transfection to silence the expression of PGC1α.The cell groups included control,Lira(100 nmol/L),PA(200 nmol/L),PA+Lira,scrambled siRNA,scrambled siRNA+Lira,siRNA PGC1α,and siRNA PGC1α+Lira groups(n=3).After corresponding treatments were given,quantitative PCR and Western blotting were employed to detect the mRNA and protein expres-sion levels of UCP-1,Prdm16,Agt,and adiponectin,as well as AMPK and p-AMPK.Results Compared to the control group,the PA group had significantly increased expression of Agt and adiponectin but decreased UCP-1 and Prdm16 at protein and mRNA levels,and the Lira group showed obviously increased protein and mRNA levels of UCP-1 and Prdm16 but decreased Agt and adiponectin levels(P＜0.05).Addition of Lira treatment resulted in increments in UCP-1 and Prdm16 while declines Agt and adiponectin at both mRNA and protein levels when compared with the levels in the PA group(P＜0.05).In comparison to the scrambled siRNA group,the siRNA PGC1α group showed decreases in UCP-1 and Prdm16 expression,accompanied by increa-ses in Agt and adiponectin levels(P＜0.05),similar results were observed in the scrambled siRNA+Lira group(P＜0.05).The p-AMPK/AMPK ratio was significantly increased in the scrambled siRNA+Lira group(1.415±0.176 vs 0.837±0.049,P＜0.05),but decreased in the siRNA PGC1α group(0.534±0.035 vs 0.837±0.049,P＜0.01)when compared with the scram-bled siRNA group.Conclusion Lira promotes adipocyte browning and improves lipid metabolism disorders in a high-fat environment by activating the AMPK/PGC1α signaling pathway.

Objective:To observe the morphological characteristics of dome-shaped macula (DSM) and macular hole (MH) in high myopia by optical coherence tomography (OCT), to further explore the correlation between DSM and MH.Methods:A retrospective case-control study. From April 2021 to December 2023, 963 eyes of 503 patients with high myopia (myopic diopter ≥6.00 D) in Department of Ophthalmology of the Fourth Hospital of Hebei Medical University were enrolled in the study. The age of patients ranged from 5 to 89 years old, with the mean age of (48.91±16.69) years. Diopter was -6.00 to -26.00 (-10.49±3.15) D. All eyes were examined by OCT. The width and height of DSM, subfoveal choroidal thickness (SFCT), inner port diameter and base diameter of MH were measured by software on OCT. According to the OCT image features, DSM was divided into horizontal and vertical oval-shaped DSM, and symmetrical round DSM. According to the presence or absence of DSM, the eyes were divided into DSM group and non-DSM group. Then, the affected eyes with MH were divided into DSM with MH group and non-DSM with MH group. The incidence of DSM, the incidence of MH in the DSM group and the non-DSM group, the inner port diameter of MH, the base diameter of MH, SFCT, and the location of retinoschisis (RS) in the DSM with MH group and the non-DSM with MH group were observed. Independent sample t test or non-parametric Mann-Whitney U test was used for comparison between groups. Pearson correlation analysis was used to analyze the related factors of MH inner port diameter, base diameter and DSM width, height, height/width ratio. Results:Among the 963 eyes, the DSM group and the non-DSM group were 266 (27.6%, 266/963) and 697 (72.4%, 697/963) eyes. Compared with the non-DSM group, patients in the DSM group were older ( Z=-11.302), had higher degree of myopia ( Z=-8.944), thinner SFCT ( Z=-16.244), and higher incidence of MH ( χ2=8.828), and the differences were statistically significant ( P<0.05). Compared with non-DSM with MH group, the patients in DSM with MH group were older ( t=2.610), higher myopia diopter ( t=3.593), and thinner SFCT ( t=3.505), the differences were statistically significant ( P<0.05). There was no significant difference in the number of eyes in the epiretinal membrane between the two groups ( χ2=0.119, P=0.730). In the DSM with MH group, RS mostly occurred in the outer retina with a large range, while in the non-DSM with MH group, RS mostly occurred in the outer and inner retina with a small range. There was a statistically significant difference in the number of eyes at different positions of RS between the two groups ( χ2=25.131, P<0.05). The results of correlation analysis showed that there was no correlation between the inner port and base diameter of MH and the width, height, height/width ratio of DSM ( P>0.05). Conclusions:Compared with high myopia patients without DSM, patients with DSM are older, have more severe myopia and thinner SFCT. In DSM patients with MH, RS often occurs in the outer retina and has a large range. There was no significant association between DSM morphology and MH size.

Objective To explore the correlation between triglyceride glucose(TyG)index and per-cutaneous coronary intervention(PCI)following drug treatment in elderly patients with unstable angina pectoris(UAP).Methods A total of 221 elderly UAP patients admitted to the Hyperbaric Oxygen Department of the First Medical Center of Chinese PLA General Hospital from March 2016 to March 2024 were enrolled,and based on the tertiles of the TyG index,they were divided into low,medium and high TyG index groups(the index:≤8.48,8.49-8.92,＞8.92;with 74,74 and 73 cases,respectively).Clinical data of all patients were collected,and whether undergoing PCI after discharge was defined as the endpoint event.The follow-up ended on May 10,2024.The clini-cal data were compared in the three groups.Kaplan-Meier survival curves were plotted to compare the survival rates among the groups,and Cox proportional hazards regression model was em-ployed to analyze the influencing factors for occurrence of endpoint event.Results There were significant differences in the three groups in terms of TyG index,BMI,diabetes,FPG,TC,TG,LDL-C,HDL-C,HbA1c,NT-proBNP,and incidence of endpoint event(P＜0.05,P＜0.01).Univa-riate Cox proportional hazards regression analysis showed that the TyG index,diabetes,and HbA1c were risk factors for endpoint events in elderly patients with UAP(HR=2.523,95％CI:1.593-3.996;HR=2.543,95％CI:1.263-5.118;HR=1.434,95％CI:1.159-1.774).Further multivariate Cox proportional hazards regression analysis showed that,after adjusting for diabetes and HbA1c,the TyG index was an independent risk factor for PCI after discharge in UAP patients(HR=2.023,95％CI:1.209-3.384).Conclusion In elderly UAP patients receiving drug treat-ment,a high TyG index is positively correlated with undergoing PCI after discharge,and the index is an independent risk factor for PCI in them.

Objective:To establish an arsenic free fully automatic online digestion iodine analyzer detection method for urinary iodine (hereinafter referred to as the method).Methods:Based on the principle of iodine catalyzed antimony cerium redox reaction, a fully automatic online digestion iodine analyzer was used to determine the iodine content in urine. The effectiveness of the method in terms of detection limit, precision, accuracy (determination of urinary iodine primary standard reference materials GBW09108z and GBW09110f and spiked recovery experiment), and interference experiments was validated. The method was compared with the arsenic cerium catalytic spectrophotometry method recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:The linear range of the method was 0 - 300 μg/L, with a correlation coefficient │ r│> 0.999 5. The qualitative and quantitative detection limits were 7.41 and 18.01 μg/L, respectively. The relative standard deviation ( RSD) of urine samples with different iodine concentrations ranged from 1.0% to 1.7%. The results of the determination of iodine concentrations in urine using standard substances GBW09108z and GBW09110f were within the given standard range, with RSD < 2.5%. The range of spiked recovery rates for urine samples with different iodine concentrations was 101.3% to 104.8%, with an overall average spiked recovery rate of 103.0%. The average concentration of the baseline iodine standard solution was determined to be 116.21 μg/L, and the relative error of the concentration determination with the addition of interfering substances was less than 5.0%. The comparison results showed that there was no statistically significant difference in the measurement results between the two methods ( t = - 0.06, P = 0.952). Conclusions:The method adopts automated detection, which is simple to operate, labor-saving, and does not require the use of arsenic trioxide. It has high precision and accuracy, and is suitable for detection of large quantities of samples.

The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.

The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.