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.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 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 Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated 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 therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

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.

Extensive tissue and organ defects caused by major trauma and burns are common problems in clinical practice. Recombinant human collagen biomaterials, with advantages including impeccable biocompatibility, customization, stable amino acid sequence, low immunogenicity, and inherent biodegradation, have been widely used in the field of tissue engineering and have broad clinical application prospects. This paper briefly summarizes the design and preparation methods, processing techniques of recombinant human collagen biomaterials and their application in the field of tissue engineering, as well as the latest research advances.

Objective:To prepare the bacterial outer membrane vesicles(OMV)that can express programmed death ligand 1(PD-L1)nanobody on surface,and to discuss its structural characteristics,cell compatibility,intracellular distribution,and its blocking effect on the programmed cell death protein-1(PD-1)/PD-L1 signaling axis.Methods:The pET28a-ClyA-PD-L1nb prokaryotic expression vector was constructed and transformed into Escherichia coli BL21(DE3)competent cells;the OMV was isolated from the BL21(DE3)monoclonal colonies transformed with the PD-L1nb expression vector by ultracentrifugation;the protein purification was performed using the histidine(His)tag;transmission electron microscope and nanoparticle size analyzer were used to analyze and identify the OMV;the OMV isolated from the BL21(DE3)monoclonal colonies transformed with the PD-L1nb expression vector was used as experimental group;the OMV isolated from the untransformed BL21(DE3)monoclonal colonies was used as control group;Western blotting method was used to detect the expression levels of ClyA-PD-L1nb fusion protein in the OMV in two groups;cell counting kit-8(CCK-8)assay was used to detect the activities of mouse macrophage RAW 264.7 cells,mouse triple-negative breast cancer 4T1 cells,and human embryonic kidney HEK293T cells after treated with OMV;fluorescence imaging technology was used to observe the tumor cell endocytosis of OMV;flow cytometry was used to detect the binding effect of OMV to the PD-L1 on surface of the tumor cells in PBS group,OMV-PD-L1nb group,and aPD-L1+OMV-PD-L1nb group.Results:The sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)results showed that after induction of Escherichia coli,significantly thickened protein bands appeared near the predicted relative molecular mass(about 49 000),and after purification,no obvious impurity proteins existed in the lanes;the OMV-PD-L1nb with a size of about 120 nm was isolated by ultracentrifugation,and it presented a uniform spherical structure under transmission electron microscope;the Western blotting results showed that the specific band of ClyA-PD-L1nb was detected in the OMV in experimental group;the CCK-8 assay results showed that after treated with different concentrations of OMV,the viabilities of the RAW 264.7 cells,4T1 cells,and HEK293T cells were all close to 100％;the fluorescence imaging results showed that OMV-PD-L1nb was endocytosed by 4T1 cells and dispersed in the cytoplasm;compared with OMV-PD-L1nb group,the average fluorescence intensity in the cells in aPD-L1+OMV-PD-L1nb group was significantly decreased(P＜0.001).Conclusion:The OMV surface-displaying PD-L1nb,OMV-PD-L1nb,is successfully prepared and isolated;OMV-PD-L1nb shows good compatibility on mouse macrophage cells,tumor cells,and human embryonic kidney cells,can be endocytosed by tumor cells,and successfully blocks the PD-1/PD-L1 signaling pathway.

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.

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.

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.

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.