Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Phage immunoprecipitation sequencing (PhIP-Seq) is a high-throughput and low-cost method for analyzing the specific binding of target proteins to peptide libraries. The method uses oligonucleotide library synthesis (OLS) to encode proteome-scale peptide libraries for display on phages, and then immunoprecipitates these library phages with target proteins (such as antibodies) for subsequent analysis by high-throughput DNA sequencing. PhIP-Seq enables the screening of peptide targets that react specifically with hundreds of proteins or pathogens. PhIP-Seq has been successfully applied in various fields such as disease detection, screening of autoimmune disease biomarkers, vaccine development, and allergen detection, becoming a high-throughput diagnostic technology. This article systematically describes the development, applications, and result evaluation of PhIP-Seq, in order to gain a more comprehensive understanding of the application and future development prospects of this technology in various fields.
Peptide Library ; Humans ; Immunoprecipitation/methods* ; High-Throughput Nucleotide Sequencing/methods* ; Bacteriophages/genetics*

This study investigated the therapeutic effects and mechanisms of medical ozone on sepsis- associated kidney injury (S-AKI) induced by lipopolysaccharide in mice. Using enzyme-linked immunosorbent assay, renal histopathological evaluation, detection of renal function biochemical indicators, immunofluorescence staining, and Western blot analysis, the effects of intraperitoneal injection of ozone on inflammation, coagulation, and renal tissue in mice were systematically detected.The results demonstrated that ozone treatment significantly reduced circulating levels of the specific markers (citrullinated histone H3 and myeloperoxidase-DNA complexes) from neutrophil extracellular traps (NETs) in S-AKI mice, with a suppression on inflammatory and tissue factor expression in renal tissue. Furthermore, ozone effectively improved microcirculation dysfunction, reduced tubular damage and interstitial inflammatory infiltration, thereby alleviating pathological changes of kidneys of S-AKI mice. Mechanistic studies revealed that ozone enhances phagocytic clearance of tissue factor-rich microparticles (TF-MPs) by activating the 5'-monophosphate-activated protein kinase (AMPK) / scavenger receptor (SR)-A1 signaling pathway in macrophages. In Sr-a1-/- mice, renoprotective effect of ozone was completely abolished, confirming the critical role of SR-A1 in this mechanism. In summary, this study demonstrates that medical ozone promotes macrophage clearance of TF-NETs complexes through the AMPK/SR-A1 signaling axis, exerting dual protective effects on mice through anti-inflammatory action and microcirculation improvement, which provides novel intervention targets and therapeutic strategies for S-AKI treatment.

Objective To compare the prognosis of differentiated bladder urothelial carcinoma(BUC)and common BUC.Methods A retrospective study was conducted to select the clinical data of 236 patients with common BUC and 40 patients with differentiated BUC who underwent radical cystectomy for muscular invasive bladder cancer from January 2012 to March 2023 in the Second Hospital of Lanzhou University.A propensity score matching(PSM)method was used to reduce selection bias in observational studies.The Kaplan-Meier method was used to compare overall survival(OS)and disease-specific survival(CSS)between the two groups.The COX propor-tional risk model was used to analyze the effect of differentiated BUC on overall mortality risk(OMR)and cancer-specific mortality risk(CSMR).Results The median follow-up time was 30.5months,ranged from 4months to 134months.Before PSM,there were signifi-cant differences in overall mortality(OM)and cancer-specific mortality(CSM)between the differentiated BUC and the common BUC(P were 0.008,0.011).The Kaplan-Meier survival curve analysis showed the OS(P=0.020)and CSS(P=0.023)of common BUC were better than those of differentiated BUC.Multivariate COX regression analysis showed that the OMR and CSMR of differentiated BUC increased by 75％(P=0.013)and 79％(P=0.029)compared with common BUC.After PSM,there was no significant difference in OM(P=0.217)and CSM(P=0.134)between the two groups.Kaplan-Meier survival curve analysis showed that there was no signifi-cant difference in OS(P=0.510)and CSS(P=0.340)between common BUCand differentiated BUC.Multivariate COX regression a-nalysis showed that there were no significant differences in OMR and CSMR between the two groups(all P＞0.05).Conclusion After PSM,the prognosis of differentiated BUC was not found to be inferior to that of the common BUC.Furthermore,the specific type of differ-entiation was not identified as an individual predictor of a worse prognosis.

Objective To compare the prognosis of differentiated bladder urothelial carcinoma(BUC)and common BUC.Methods A retrospective study was conducted to select the clinical data of 236 patients with common BUC and 40 patients with differentiated BUC who underwent radical cystectomy for muscular invasive bladder cancer from January 2012 to March 2023 in the Second Hospital of Lanzhou University.A propensity score matching(PSM)method was used to reduce selection bias in observational studies.The Kaplan-Meier method was used to compare overall survival(OS)and disease-specific survival(CSS)between the two groups.The COX propor-tional risk model was used to analyze the effect of differentiated BUC on overall mortality risk(OMR)and cancer-specific mortality risk(CSMR).Results The median follow-up time was 30.5months,ranged from 4months to 134months.Before PSM,there were signifi-cant differences in overall mortality(OM)and cancer-specific mortality(CSM)between the differentiated BUC and the common BUC(P were 0.008,0.011).The Kaplan-Meier survival curve analysis showed the OS(P=0.020)and CSS(P=0.023)of common BUC were better than those of differentiated BUC.Multivariate COX regression analysis showed that the OMR and CSMR of differentiated BUC increased by 75％(P=0.013)and 79％(P=0.029)compared with common BUC.After PSM,there was no significant difference in OM(P=0.217)and CSM(P=0.134)between the two groups.Kaplan-Meier survival curve analysis showed that there was no signifi-cant difference in OS(P=0.510)and CSS(P=0.340)between common BUCand differentiated BUC.Multivariate COX regression a-nalysis showed that there were no significant differences in OMR and CSMR between the two groups(all P＞0.05).Conclusion After PSM,the prognosis of differentiated BUC was not found to be inferior to that of the common BUC.Furthermore,the specific type of differ-entiation was not identified as an individual predictor of a worse prognosis.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To optimize the technical parameters used for embryo transfer in golden hamsters,and explore the optimal number and developmental period of transplanted embryos for golden hamster pregnancy recipients.Methods We established a population of true pregnant albino golden hamster embryo transfer recipients and compared the effects of different embryonic developmental stages,recipient embryo reduction,and secondary transfer recipients on litter yield,donor embryo yield,and offspring survival rate.Results Compared with wild-type golden hamster transplant recipients,true pregnancy albino recipients allowed the origin of the offspring to be determined quickly,and were suitable for various reproductive experimental programs based on embryo transfer.The use of fertilized eggs or two-cell embryos had no significant impact on the transfer effect(P＞0.05);however,the rate of donor embryos was significantly increased in the recipient embryo-reduction group(22％,P＜0.05).The second transfer recipient's non-pregnancy rate was significantly increased(42％,P＜0.01).The highest embryo yield rate(27％,P＜0.01)and normal survival rate(89％)occurred with the transfer of 6～10 embryos.Conclusions The transfer of 6～10 donor embryos may improve the yield and survival rate of donor embryos.Here,we successfully established an embryo transfer method using pregnant albino golden hamsters as recipients,thus providing technical support for the application and development of gene modification models in golden hamsters.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective To establish an ideal model of the mitral valve,including the left heart and blood,and study the motion characteristics of the mitral valve in blood flow using the fluid-structure interaction(FSI)simulation.Methods Based on anatomical parameters,models of the mitral valve,left heart,and blood were established.The finite-elements combined immersed boundary method was used for FSI to simulate the motion of the mitral valve using the LS-DYNA software.Morphological,mechanical,and hemodynamic parameters were compared with those obtained from structural simulations.Results The morphological results of the mitral valve from the two simulations differed significantly,and the FSI results matched the ultrasound images.The stress distributions of the leaflets in the FSI and structural simulations were consistent.The maximum first principal stresses calculated by FSI and structural simulations were 1.48 MPa and 1.53 MPa,respectively,with a relative error of 3.27％.The fluid field in the left heart was complex with vortex structures,and the maximum mitral flow velocity was 1.02 m/s during diastole,consistent with the physiological data of healthy humans(0.89±0.15 m/s).Conclusions The morphological results of the mitral valve obtained from the FSI simulation were closer to those in the physiological state.FSI simulations can provide flow patterns that are indispensable for clinical diagnosis.Structural simulations are more efficient for studying leaflet stress distribution.

Objective: To investigate the changes of osteogenic genes and osteogenic capacity after overexpression of bone morphogenetic protein 2(Bmp2) in rat adipose stem cells． Methods: Bmp2 was transfected into rat adipose stem cells by electrotransfection，and the blank group was used as control．The cells were divided into blank group ( Control group) ，empty load group (Vector group) ，osteogenesis induction group (Inducement group) ，and overexpression group (Bmp2 group) ．Western blot，qRT-PCR and immunofluorescence were used to compare the expression of osteogenic genes，and alkaline phosphatase staining and alizarin red staining were used to observe cobalt sulfide precipitation and calcium salt deposition. Results : Western blot and qRT-PCR showed that the expression of Bmp2，Bmp4，OPN，OCN，Runx2，P-Smad1 /5，Dlx2，and BSP was significantly higher compared to the Control group (P ＜0. 05 ) ，while the expression of Smad1 /5 was not statistically different． Immunofluorescence showed that the fluorescence intensity of OPN and Runx2 was significantly higher compared to the Control group (P ＜0. 05) ．The alizarin red staining and alkaline phosphatase staining showed that the Bmp2 group had increased pericellular calcium salt deposition，increased cobalt sulfide precipitation，and enhanced alkaline phosphatase activity compared to the Control group． Conclusion Overexpression of Bmp2 enhances osteogenic gene expression in adipose stem cells and improves their osteogenic ability.