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.

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

Objective:To assess the safety and feasibility of selectively preserving the first branch of the right gastro-omental artery using bidirectional dissection in laparoscopic pylorus-preserving gastrectomy (LPPG).Methods:In this retrospective analysis, we studied preoperative, intraoperative, postoperative, and follow-up data of 30 patients with early gastric cancer treated in the Department of Gastric Cancer in Zhejiang Cancer Hospital (28 patients), Department of Gastrointestinal Surgery in Jiaxing Second Hospital (one patient) and Department of Gastrointestinal Surgery in Hangzhou Red Cross Hospital (one patient) who had undergone selective preservation of the first branch of the right gastro-omental artery during LPPG. The main variables studied were as follows: (1) intraoperative preservation of the first branch of the right gastro-omental artery; (2) the overall surgical situation; and (3) postoperative small bowel follow-through and endoscopy findings.Results:LPPG with selective preservation of the right gastro-omental artery vascular branch was achieved in all 30 of the study patients. The mean operation time was (244.3±29.3) minutes and the median intraoperative blood loss 50 (20–200) mL. The median tumor diameter was 1.2 (0.5–3.6) cm and an average of 32.3±11.6 lymph nodes were dissected. The overall median number of positive lymph nodes was 0 (0–6), and of No. 6 lymph nodes 5.1±1.5. Postoperative feeding resumed at an average of 5.2±0.5 days and the postoperative hospital stay averaged 8.4±3.4 days. Pathological stages were as follows: T1a (14 cases), T1b (10 cases), and T2 (6 cases). Small bowel follow-through imaging showed good results in 28 patients 5 days post-surgery, the remaining two exhibiting good results 9 days post-surgery. There were no instances of delayed gastric emptying, and only one patient (3.3%) developed intra-abdominal infection (resolved with conservative treatment).Conclusion:Selective preservation of the right gastro-omental artery during laparoscopic early gastric cancer surgery is a safe and feasible procedure for treating early mid-gastric body cancer with pyloric preservation.

Objective:To assess the safety and feasibility of selectively preserving the first branch of the right gastro-omental artery using bidirectional dissection in laparoscopic pylorus-preserving gastrectomy (LPPG).Methods:In this retrospective analysis, we studied preoperative, intraoperative, postoperative, and follow-up data of 30 patients with early gastric cancer treated in the Department of Gastric Cancer in Zhejiang Cancer Hospital (28 patients), Department of Gastrointestinal Surgery in Jiaxing Second Hospital (one patient) and Department of Gastrointestinal Surgery in Hangzhou Red Cross Hospital (one patient) who had undergone selective preservation of the first branch of the right gastro-omental artery during LPPG. The main variables studied were as follows: (1) intraoperative preservation of the first branch of the right gastro-omental artery; (2) the overall surgical situation; and (3) postoperative small bowel follow-through and endoscopy findings.Results:LPPG with selective preservation of the right gastro-omental artery vascular branch was achieved in all 30 of the study patients. The mean operation time was (244.3±29.3) minutes and the median intraoperative blood loss 50 (20–200) mL. The median tumor diameter was 1.2 (0.5–3.6) cm and an average of 32.3±11.6 lymph nodes were dissected. The overall median number of positive lymph nodes was 0 (0–6), and of No. 6 lymph nodes 5.1±1.5. Postoperative feeding resumed at an average of 5.2±0.5 days and the postoperative hospital stay averaged 8.4±3.4 days. Pathological stages were as follows: T1a (14 cases), T1b (10 cases), and T2 (6 cases). Small bowel follow-through imaging showed good results in 28 patients 5 days post-surgery, the remaining two exhibiting good results 9 days post-surgery. There were no instances of delayed gastric emptying, and only one patient (3.3%) developed intra-abdominal infection (resolved with conservative treatment).Conclusion:Selective preservation of the right gastro-omental artery during laparoscopic early gastric cancer surgery is a safe and feasible procedure for treating early mid-gastric body cancer with pyloric preservation.

At present, there is still a big gap between China and developed countries in the field of high-end medical devices, and the ability of independent innovation needs to be improved. In order to comprehensively cultivate innovative talents in the field of medical devices and promote the development of the field of medical devices, the biomedical engineering major of Chongqing Medical University has put forward a "Trinity" innovative talent training system in the field of medical devices, including the teaching of theoretical knowledge, the improvement of practical skills and the guarantee of the innovation system, and established a four stage curriculum system framework of "Perception-Understanding-Enlightenment-Challenge" to form a characteristic course with ultrasonic treatment equipment as the main line. After three years of practice, the results of this training mode show that the innovative ability, professional connotation construction quality and employment postgraduate entrance examination rate of our college students have been steadily improved. The exploration of this talent training mode has reference significance for the cultivation of innovative talents in the field of medical devices in higher medical colleges and universities in China.

Objective: To explore susceptibility genes for autism spectrum disorders (ASD). Methods: Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates. Results: A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2 (0.8146)] and four medium-confidence genes [ERBB2 (0.1322), LAMC3 (0.1117), PPFIA4 (0.1059), DISC1 (0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes. Conclusion Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Objective:To explore the changes of bone mineral density (BMD) and type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31 hiEmcn hi) in long bone from ovariectomized (OVX) mice compared withSham group. Methods:C57BL/6Jwild-type mice were used for experiments and bone tissuewas collected. Eight-week-old female mice were randomly divided into bilateral ovariectomy (OVX) and a sham operation (Sham). The bilateral ovaries were exposed and removed in the OVX group. In the sham group, the ovaries were only exposed but left intact. After 4weeks, these mice were killed for experiment and the femurs were collected for Micro CT scanning in order to observe the changes of bone mineral density (BMD) and trabecular indexes, including bone volume (BV), total volume of interest (TV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N). The fresh tibia of each mouse was fixed, decalcified, dehydrated and embedded for immunostaining. All experimental data were analyzed with t-test. Results:Mouse femora from two groups were dissected at 4 week time points, and the attached soft tissue was completely removed for Micro CT scanning. BMD in OVX is 0.11±0.01 g/cm 3 and 0.21±0.01 g/cm 3 in Sham, which indicated the BMD in OVX significantly decreased. The results showed significant difference between the groups ( P=0.001). The microarchitecture in trabecular bone changed. BV/TV in OVX is 11.52%±1.77% and 25.87%±1.31% in Sham, which indicated the BV/TV in OVX significantly decreased. The results showed significant difference between the groups ( P<0.05). Tb.N in OVX is 1.67±0.33/mm and 2.95±0.82/mm in Sham, which indicated the Tb.N in OVX slightly decreased. The results showed no significant difference between the groups ( P=0.066). Tb.Th in OVX is 0.06±0.01 mm and 0.07±0.01 mm in Sham, which indicated the Tb.Th in OVX significantly thinned. The results showed significant difference between the groups ( P=0.021). Tb.Sp in OVX is 0.29±0.15 mm and 0.19±0.01 mm in Sham, which indicated the Tb.Sp in OVX significantly increased. The results showed significant difference between the groups ( P<0.05). In the groups BMD decreased and trabecular microstructure was broken. Both BMD and trabecular indexes (BV/TV, Tb. Th, Tb. Sp) showed significant changes in OVX group compared with Sham ( P<0.05) except Tb.N. We next examined the expression of CD31 and EMCN via immunostaining in order to observe the changes of type H vessel.By immunostaining, the percentage of HV/TV in OVX group was 9.14%±0.99% and 29.33%±1.22% in the sham-operated mice. Dramatically decreased type H vessels in the metaphysis of OVX mice were observed compared with that of Sham control mice. The results showed significant difference between the groups ( P<0.05). Conclusion:In this study, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by reduced BMD, which indicatedtype H vessel involved in the occurrence of postmenopausal osteoporosis.