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 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

AIM:To investigate the effects of exercise preconditioning(EP)combined with electroacupunc-ture(EA)on learning and memory ability of rats with vascular dementia(VD),and to explore role of hippocampal ferrop-tosis in this process.METHODS:Seventy-two male SD rats were randomly divided into non-EP group and EP group,with 36 rats in each group.The rats were subjected to EP,and subsequently to establish the VD model.The rats from non-EP group were randomly divided into sham group,model group(VD group)and VD-EA group,each with 12 rats,while those in EP group were randomly divided into EP-sham group,EP-VD group and EP-VD-EA group,each with 12 rats.All rats in EP group underwent 4 weeks of swimming exercise training,5 d per week,30 min per day.At the end of the 4th week,the rats in VD,EP-VD,EP-VD-EA and VD-EA groups were used to induce the VD model,and the rats in sham and EP-sham groups received a sham surgery to simulate the VD model.On the 7th day after successful modeling,the rats in EP-VD-EA and VD-EA groups were treated with EA for 4 weeks,6 d per week,30 min per day.At the end of the inter-vention,the learning and memory ability of the rats was evaluated using Morris water maze.Neuron morphology in the CA1 area of rat hippocampus was observed through Nissl staining.Ferrous ion(Fe2+),malondialdehyde(MDA)and re-duced glutathione(GSH)contents in the rat hippocampal tissues were quantified using the colorimetric assay.The expres-sion levels of ferroptosis-related proteins,nuclear factor E2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4),in the hippocampal tissues were quantified by Western blot method.RESULTS:Compared with sham group,the rats in VD group exhibited longer mean evasion latency and decreased number of traversals across the plateau(P<0.01).The neurons in the CA1 region of the hippocampus were loose and disorganized,exhibiting an irregular cellular morphology.The hippocampal Fe2+and MDA content was elevated,and the GSH content was reduced(P<0.01).The protein levels of hippocampal Nrf2 and GPX4 were decreased(P<0.01).Compared with VD group,the rats in EP-VD,EP-VD-EA and VD-EA groups showed a shorter average escape latency and an increased number of traversals across the plateau(P<0.05).Neurons in the hippocampal CA1 area were more neatly arranged,showing regular cellular morphology.The hip-pocampal Fe2+and MDA contents of the rats in EP-VD group were significantly reduced(P<0.01),while the GSH content was elevated(P<0.05).Hippocampal Fe2+and MDA contents were significantly reduced and GSH contents were signifi-cantly increased in EP-EA and EA groups(P<0.01).The protein levels of hippocampal Nrf2 and GPX4 in EP-VD,EP-VD-EA and VD-EA groups were significantly increased(P<0.01).CONCLUSION:Exercise preconditioning combined with EA improves learning and memory ability in VD rats by reducing hippocampal intra-neuronal iron overload,maintain-ing organismal redox homeostasis,and inhibiting ferroptosis.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Objective Apply modified bilateral carotid artery ligation to establish a VD rat model to observe changes in cerebral blood flow and expression of angiogenic proteins.Methods Thirty-six SD male rats were randomly divided into a sham group(n = 18)and model group(n = 18).In the sham group,only the bilateral carotid artery was isolated without ligation,whereas in the model group,the bilateral carotid artery was ligated to establish the VD model.The Morris water maze behavior test was applied before and 14 days after modeling.Variation in cerebral blood flow was detected by laser speckle contrast imaging.Protein expression of HIF-1α,VEGF,and HO-1 was detected by Western Blot.IL-4 and IL-10 contents were measured by ELISA.Results At 14 days after modeling,escape latency was significantly prolonged and the frequency of crossing the platform had significantly decreased in the model group compared with the sham group(P<0.05).At 2 hours,3 days,and 7 days after modeling,cerebral blood flow in the model group was significantly lower than that in the sham group(P<0.05).At 14 and 21 days after modeling,no significant difference was found in cerebral blood flow between sham and model groups(P>0.05).In the model group,cerebral blood flow was decreased to a minimum at 2 hours after modeling(P<0.05)and then began to recover.The peak of recovery occurred at 3～7 days after modeling and returned to the level before modeling on day 14 after modeling.At postoperative day 21,expression of HIF-1α,VEGF,and HO-1 proteins in the hippocampus of the model group was increased remarkably(P<0.05)and the serum contents of IL-4 and IL-10 in the model group were significantly increased compared with those in the sham group(P<0.05).Conclusions The variation in cerebral blood flow in the VD rat model established by the modified bilateral carotid artery ligation was dependent on time.At postoperative day 21,HIF-1α,VEGF,and HO-1 in the hippocampus were increased significantly,which was accompanied by increased levels of IL-4 and IL-10.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective:To recognize virus electron microscopic (EM) images automatically with deep learning techniques and to select an appropriate network for virus EM image classification.Methods:Multiple classic convolutional neural networks, such as AlexNet, VGG, ResNet, DenseNet, SqueezeNet, MobileNet, and ShuffleNet, were used to classify the seven classes of virus electron microscope images by increasing the network depth increasing the network depth and adjusting the learning rate, adjusting the learning rate, batch size and other parameters.Results:Overall, DenseNet169 achieved the best performance with 91.9% accuracy, 90.1% sensitivity and 98.6% specificity. In particular, the model performed best in parvovirus recognition. The precision, sensitivity, specificity, and F1 of papilloma virus, herpes virus, pox virus and rotavirus, were above 90%, even close to 100%, but the precision of adenoviruses and the sensitivity of polyomaviruses were not satisfied, leading to corresponding low F1 value. At the same time, Lightweight network ShuffleNet outperformed AlexNet and VGG deep networks with fewer parameters and fewer FLOPs and could achieve comparable result to ResNet with about 15 times fewer parameters and 90 times fewer FLOPs; Compared with DenseNet, Shufflenet sacrificed recognition performance in the acceptable range to achieve about 10 times fewer parameters and 80 times fewer FLOPs.Conclusions:Deep networks DenseNet169 could realize automatic recognition of virus electron microscopic images with the optimal performance and lightweight networks shuffleNet_v2_x0_5 could achieve suboptimal performcane with fewer parameters and FLOPs. In practical applications, tradeoffs can be made between deep networks and lightweight networks based on specific conditions.

Objective To evaluate the effect of sevoflurane on liver injury in a pig model of hemorrhagic shock.Methods Twenty-four Bama miniature pigs of both sexes,weighing 20-25 kg,aged 3-5 months,were equally randomized into 3 groups using a random number table:sham operation group (group S);hemorrhagic shock group (group HS);sevoflurane group (group Sev).Hemorrhagic shock was induced by withdrawing 40％ of blood volume from the right femoral artery within 15 min (30 ml/kg) in HS and Sev groups.The animals inhaled 2％ sevoflurane for 30 min after establishment of the model in group Sev.Before hemorrhagic shock (T0),and at 30,60,90,120,180 and 240 min after hemorrhagic shock (T1-6),blood samples were collected from the femoral artery for determination of plasma alaninc aminotransferase (ALT) and betaine-homocysteine S-methyltransferase (BHMT) concentrations (by enzymelinked immunosorbent assay).After blood sampling at T6,the animals were sacrificed,and the right lobes of livers were removed for examination of the pathological changes with light microscope.Results Compared with group S,the plasma ALT concentrations were significantly increased at T4-6,the plasma BHMT concentrations were significantly increased at T3-6 (P＜0.05),and significant liver pathological changes were observed in HS and Sev groups.Compared with group HS,the plasma ALT concentrations were significantly decreased at T4-6,the plasma BHMT concentrations were significantly decreased at T3-6 (P＜0.05),and the liver pathological changes were significantly attenuated in group Sev.Conclusion Sevoflurane can mitigate liver injury in a pig model of hemorrhagic shock.

To screen interaction proteins of CVB3 VP3 from cDNA library of human heart ,yeast two hybridization was conducted in this study .The bait plasmid pGBKT7-VP3 was constructed ,VP3 fusion protein and its self-activation in AH109 yeast cells was then detected .The positive clones were confirmed by PCR amplification of cDNA inserts ,Alu I digesting ,DNA sequencing ,and Blasting were used to sort positive colonies to eliminate duplicates .Positive clones were confirmed by one-to-one yeast two hybridization ,and them were sequenced and analyzed for homology .Theα-galactosidase assay was performed to detect the interaction strength .Totally ,10 positive proteins interacting with VP3 of CVB3 were obtained by homology analy-sis,namely,EIF4A2,HADHB,GAPDH,ASPG,ACTA1,TNNI3,CKM,LMOD3,ERGIC1,and ALDH2.The strength of interactions between VP3 and 10 candidate proteins were proved byα-galactosidase assay .This study will contribute to explore the CVB3 VP3 function on molecular level and provides some new clues to explain the pathogenic mechanism of myo-carditis and cardiomyopathy .

Objective Measuring the displacement and deformation of the fifth screw under different tensile force before or after adultal internal fixation with compressing steel plate for femoral fractuer by digital speckle correlation method.And analysis of the displacement and deformation after reducing the number of screws.Aimed at providing a theoretical basis for clinical femoral internal fixation with compressing steel plate about the number of screws. Methods Taking the antisepsis femoral specimen of grown-ups, embedding and fixing with tooth powder after removing the soft tissue, producing a fixed model in the 1/2 femur.Fixing steel plate below the lateral femur subperiosteal with five screws through the fourth floor of cortical bone on both sides of the fractures, samples were divided into 10 states, group A-J were measured by orders, under the rally of 400 N,500N , measuring the displayment of the fifth screw with CSS-44100-e-universal test machine for loading rally experiment ,and automatic data processing. Results For analysis of variance, the mean displacement measurements of the fifth screw under rally of 400N,500N, B-J group and A group have significant differences(P<0.05). The mean deformation measurements of the fifth screw under rally of 400N,500N, group A and group F-J group have significant differences(P<0.05);group A and B-E group have no significant differences.Conclusion In a certain range, the fracture displacement and the numuber of the screws show negative correlation. The screws near the fracture line for femoral compression plate internal fixation of femoral fractuer is easily broken because of the too large deformation.