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 compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

In order to understand the epidemic situation of European porcine reproductive and re-spiratory syndrome virus 1(PRRSV1)in Henan Province,molecular epidemiological investigation and virus identification were conducted on clinical specimens from some large-scale pig farms in Henan Province.RT-PCR detection and sequencing were carried out using specific primers for PRRSVI ORF5 gene.As a result,eight PRRSV1 positive samples were detected with six ORF5 gene sequences and one full gene sequence obtained.A strain of PRRSVI named as HENZMD-10 was successfully isolated using PAM cells.Based on the genetic variation analysis,the six ORF5 genes obtained were all PRRSVI.The isolated strains have relatively large ORF5 gene genetic vari-ation,belonging to different branches on the genetic evolution tree.Among them,HENJZ-11,HENJY-7,and HENJY-8 were relatively close in genetic evolution and belonged to the same branch.The genome length of HENZMD-10 isolate was 15 071 bp.Alignment analysis showed that HENZMD-10 strain shared an 89.1％of nucleotide sequence with the LV strain;62.1％and 61.5％with PRRSV2 ATCC-VR2332 strain and the American NADC30 strain,respectively.The nucleotide similarity of HENZMD-10 strain with the domestic JXA1 strain was 61.6％.The phylo-genetic analysis using complete genome sequence showed that HENZMD-10 strain was relatively close to the domestic isolated PRRSV1 NVDC-NM1-2011,LNEU12 and FJEU13 strains.The suc-cessful isolation of one PRRSV1 strain in Henan Province provides the basis for understanding the epidemic dynamics and prevention and control of PRRSV1 in China.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.

Objective To develop a rapid and accurate ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for the detection of etomidate,metomidate,propoxate,and isopropoxate in human hair.Methods Hair samples containing etomidate,metomidate,propoxate,and isopropoxate were extracted with methanol containing the internal standard orthoxine,filtered with a 0.22 μm organic filter membrane and detected vio UPLC-MS/MS.All components were separated by using a gradient elution procedure consisting of 0.01％formic acid(1 mmol/L ammonium acetate)and acetonitrile.Positive electrospray ionization was performed using multiple reaction monitoring(MRM)mode.Results The linear relationships of etomidate,metomidate,propoxate,and isopropoxate were good in the range of 0.01～1 ng/mg(r ≥ 0.997 9),with recovery rates ranging from 87.9％to 101.5％.The accuracy was between 80.0％and 110.0％.The intra-day and inter-day relative standard deviations(RSD)were 2.9％～9.6％and 3.6％～19.9％.Conclusion This method is easy to operate and has high recovery efficiencies.It is sufficiently simple and sensitive to be applied to detect etomidate,metomidate,propoxate,and isopropoxate in hair.

Objective To evaluate the efficacy and safety of amoxicillin-clavulanate(10∶1)for injection in the treatment of community-acquired pneumonia(CAP)in adult patients.Methods Eligible patients were randomized to receive amoxicillin-clavulanate(10∶1)2.2 g or ampicillin-sulbactam(2∶1)3.0 g via intravenous infusion q12h or q8h for 7 to 14 days.The primary endpoint was to the clinical efficacy 7-14 days after discontinuation of treatment.The secondary endpoints included microbiological efficacy and safety.Results All enrolled patients(n=324)were included in the full analysis set(FAS),specifically 165 patients receiving amoxicillin sodium-clavulanate potassium(10∶1)and 159 patients receiving ampicillin sodium-sulbactam sodium(2∶1).The clinical cure rate was 78.8％(130/165)for amoxicillin-clavulanate(10∶1)and 77.4％(123/159)for ampicillin-sulbactam 7-14 days after end of treatment(P＞0.05).The clinical cure rate was 87.5％(126/144)for amoxicillin-clavulanate(10∶1)and 87.4％(111/127)for ampicillin-sulbactam(2∶1)in per protocol set(P＞0.05).Therefore,amoxicillin-clavulanate(10∶1)was non-inferior to ampicillin-sulbactam in the primary endpoint in the treatment of CAP in adult patients.The overall bacterial eradication rate was 94.4％(34/36)for amoxicillin-clavulanate(10∶1)and 89.3％(25/28)for ampicillin-sulbactam(P＞0.05).The common study drug-related clinical adverse event were abnormalities of hepatic function in both the amoxicillin-clavulanate(10∶1)group(4.8％,8/165)and ampicillin-sulbactam group(3.1％,5/159)(P＞0.05).Conclusions Amoxicillin-clavulanate(10∶1)2.2 g Ⅳ infusion q12h or q8h for 7-14 days was noninferior to ampicillin-sulbactam in terms of clinical and microbiological efficacy in the treatment of CAP in adult patients.The safety of the two dosing regimens was comparable.

Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.