BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Perceptual decision making refers to the process by which individuals make choices and judgments based on sensory information, serving as a fundamental ability for human adaptation to complex environments. While traditional research has focused on perceptual decision making in isolated contexts, growing evidence highlights the profound influence of social contexts prevalent in real-world scenarios. As a crucial factor supporting individual survival and development, social context not only provides rich information sources but also shapes perceptual decision making through top-down processing mechanisms, prompting researchers to recognize the inherently social nature of human decisions. Empirical studies have demonstrated that social information, such as others’ choices or group norms, can systematically bias individuals’ perceptual decisions, often manifesting as conformity behaviors. Social influence can also facilitate performance under certain conditions, particularly when individuals can accurately identify and adopt high-quality social information. The impact of social context on perceptual decisions is modulated by a variety of external and internal factors, including group characteristics(e.g., group size, response consistency), attributes of peers (e.g., familiarity, social status, distinctions between human and artificial agents), as well as individual differences such as confidence, personality traits, and developmental stage. The motivations driving social influence encompass three primary mechanisms: improving decision accuracy through informational influence, gaining social acceptance through normative influence, and maintaining positive self-concept. Recent computational approaches have employed diverse theoretical frameworks to provide valuable insights into the cognitive mechanisms underlying social influence in perceptual decision making. Reinforcement learning models demonstrate how social feedback shapes future choices through reward-based updating. Bayesian inference frameworks describe how individuals integrate personal beliefs with social information based on their respective reliabilities, dynamically updating beliefs to optimize decisions under uncertainty. Drift diffusion models offer powerful tools to decompose social influence into distinct cognitive components, allowing researchers to differentiate between changes in perceptual processing and shifts in decision criteria. Collectively, these models establish a comprehensive methodological foundation for disentangling the multiple pathways by which social context shapes perceptual decisions. Neuroimaging and electrophysiological studies provide converging evidence that social context influences perceptual decision making through multi-level neural mechanisms. At early perceptual processing stages, social influence modulates sensory evidence accumulation in parietal cortex and directly alters primary visual cortex activity, while guiding selective attention to stimulus features consistent with social norms through attentional alignment mechanisms. At higher cognitive levels, the reward system (ventral striatum, ventromedial prefrontal cortex) is activated during group-consistent decisions; emotion-processing networks (anterior cingulate cortex, insula, amygdala) regulate experiences of social acceptance and rejection; and mentalizing-related brain regions (dorsomedial prefrontal cortex, temporoparietal junction) support inference of others’ mental states and social information integration. These neural circuits work synergistically to achieve top-down multi-level modulation of perceptual decision making. Understanding the mechanisms by which social context shapes perceptual decision making has broad theoretical and practical implications. These insights inform the optimization of collective decision-making, the design of socially adaptive human-computer interaction systems, and interventions for cognitive disorders such as autism spectrum disorder and anorexia nervosa. Future studies should combine computational modeling and neuroimaging approaches to systematically investigate the multi-level and dynamic nature of social influences on perceptual decision making.

‍ ObjectiveTo investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B （CHB） and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos（t）ide analogues （NAs）. MethodsA total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July， 2022， were enrolled as subjects. Related clinical data were collected， and according to the duration of antiviral therapy， they were divided into untreated group with 73 patients， treatment duration ≤1 year group with 91 patients， and treatment duration >1 year group with 136 patients. Serum HBV RNA load， HBV DNA load， and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups， further pairwise comparison using Bonferroni method； the chi-square test was used for comparison of categorical data； a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. ResultsThe positive rate of HBeAg was 18.3%， and among the patients with negative HBV DNA， the patients with positive HBV RNA accounted for 44.1% （86/195）. There was a significant difference in the distribution of the serum levels of HBV RNA， HBV DNA， and HBsAg between the positive HBeAg group and the negative HBeAg group （Z=10.740， 6.300， and 7.280， all P<0.05）. There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA， HBV DNA， and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group （P<0.05）. The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA， HBV DNA， and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg （r=-0.247 and -0.138， both P<0.05） and a strong negative correlation with the level of HBV DNA （r=-0.771， P<0.001）. There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg （r=0.360 and 0.442， both P<0.001）. Further stratified analysis showed that in the untreated group， there was a strong positive correlation between HBV RNA and HBV DNA （r=0.752， P<0.001） and a moderate positive correlation between HBV RNA and HBsAg （r=0.559， P<0.001）； in the treatment duration ≤1 year group， there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg （r=0.396 and r=0.388， both P<0.001）； in the treatment duration >1 year group， there was a low degree of positive correlation between HBV RNA and HBsAg （r=0.352， P<0.001）. ConclusionSerum HBV RNA is negatively correlated with the duration of treatment with NAs， and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore， it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent， with a relatively high accuracy in reflecting the level of viral replication in untreated patients.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

ObjectiveThis study aims to explore the effect of ultrasound-guided superficial parasternal intercostal plane block on the quality of recovery and postoperative analgesia in patients undergoing sternotomy cardiac surgery. MethodsA total of 64 patients undergoing sternotomy cardiac surgery were selected for this study. They were randomly divided into two groups： one group received a superficial parasternal intercostal plane block with ropivacaine （the ropivacaine group）， while the other was given normal saline （the normal saline group）. The primary outcome was the Quality of Recovery-15 （QoR-15） score on postoperative day 1 in both groups， accompanied by a comparative analysis of the pain score and opioid usage. ResultsCompared with the normal saline group， the ropivacaine group exhibited a significantly higher QoR-15 score on postoperative day 1［（89.60±13.24） vs （81.18±12.78）， P=0.012］. The numerical rating scale at rest was significantly lower［（3.03±0.72） vs （4.26±0.93）， P<0.001］， and the numerical rating scale during coughing was also significantly reduced ［（4.40±0.89） vs （5.44±1.05）， P<0.001］. Concurrently， the cumulative morphine equivalent consumption during the initial 24 h postoperatively was significantly lower in patients who were administered the ropivacaine ［14.15 （4.95～30.00） mg vs 40.50 （19.25～68.18） mg， P=0.002］， and there was also a notable decrease in the rescue analgesia ［0.00 （0.00～0.00） mg vs 0.00 （0.00～100.00） mg， P=0.007］. ConclusionUltrasound-guided superficial parasternal intercostal plane block can significantly enhance the overall quality of recovery in patients undergoing sternotomy cardiac surgery on postoperative day 1. The technique contributes to improved postoperative analgesic effects and a reduction in opioid usage， thereby facilitating early postoperative recovery.

Objective To investigate the influence of modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy on the efficacy,survival status and serum cytokeratin 19 fragment(CYFRA21-1)and neuron-specific enolase(NSE)levels in patients with advanced non-small cell lung cancer(NSCLC).Methods Forty patients with advanced NSCLC of lung-stomach yin deficiency with intense heat-toxin type were randomly divided into a control group and a study group,with 20 patients in each group.The patients in the control group were given Camrelizumab immunotherapy plus chemotherapy,and the patients in the study group were given modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy,with 21 days as a course of treatment and for a total of 4 courses of treatment.The changes of serum NSE and CYFRA21-1 levels in the two groups before and after treatment were observed,and the clinical efficacy,survival status and the incidence of toxic and side effects were compared between the two groups.Results(1)After 4 courses of treatment,the total effective rate of the study group was 70.00%(14/20),which was significantly higher than that of the control group(9/20,45.00%),but the intergroup comparison(tested by chi-square test)showed that the difference was not statistically significant(P＞0.05).(2)After 2 years of follow-up,the overall survival(OS),time to progression(TTP),and progression-free survival(PFS)of the patients in the study group were significantly prolonged compared with those in the control group(P＜0.01).(3)After treatment,the serum NSE and CYFRA21-1 levels of the patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum NSE and CYFRA21-1 levels in the study group was significantly superior to that in the control group(P＜0.01).(4)The incidence of toxic and side effects in the study group was 25.00%(5/20),which was significantly lower than that of 65.00%(13/20)in the control group,and the intergroup comparison showed that the difference was statistically significant(P＜0.05).Conclusion Modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy has satisfactory therapeutic effect on patients with advanced NSCLC,which can reduce the toxic and side effects of chemotherapy,lower the level of serum tumor markers,and prolong the survival period and time to progression(TTP)of the patients.

Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

Objective To construct and validate a predictive model based on preoperative inflammatory biomarkers,and to evaluate its ability in predicting the prognosis of patients with unresectable hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(TACE).Methods A total of 544 patients with HCC,who received TACE as the initial treatment at six medical institutions between January 2007 and December 2020,were retrospectively collected.The patients were divided into training cohort(n=376)and validation cohort(n=168).LASSO algorithm and Cox regression analysis were used to screen out the independent influencing factors and to make modelling.The model was validated based on the discrimination,calibration and clinical applicability,and the Kaplan-Meier risk stratification curves were plotted to determine the prognostic differences between groups.The likelihood ratio chi-square value,R2 value,akaike information criterion(AIC)value,C-index and AUROC value of the model were calculated to determine its accuracy and efficiency.Results The training cohort and validation cohort had 376 participants and 168 participants respectively.Multivariate analysis indicated that BCLC,tumor size,number of tumor lesions,neutrophil and prognostic nutritional index(PNI)were the independent influencing factors for postoperative overall survival(OS),with all P being＜0.05;the BCLC grade,tumor size,number of tumor lesions,NLR,PNI and PS score were the independent influencing factors for progression-free survival(PFS),with all P being＜0.05.The C-indexes of the OS and PFS models were 0.735(95％ CI=0.708-0.762)and 0.736(95％ CI=0.711-0.761)respectively,and the external validation was 0.721(95％ CI=0.680-0.762)and 0.693(95％ CI=0.656-0.730)respectively.Ideal discrimination ability of the nomogram was exhibited in time-dependent C-index,time-dependent ROC,and time-dependent AUC.The calibration curves significantly coincided with the ideal standard lines,indicating that the model had high stability and low over-fitting level.Decision curve analysis revealed that there was a wider range of threshold probabilities and it could augment net benefits.The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically between risk categories(P＜0.000 1).The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically among different risk groups(P＜0.000 1).The likelihood ratio chi-square value,R2 value,AIC value,C-index and AUROC value of the model were better than those of other models commonly used in clinical practice.Conclusion The newly-developed prognostic nomogram based on preoperative inflammatory indicators has excellent accuracy as well as excellent prediction effect in predicting the prognosis of patients with unresectable HCC after receiving TACE,therefore,it can be used as an effective tool for guiding individualized treatment and for predicting prognosis.(J Intervent Radiol,2024,33:245-258)

Objective To explore and analyze the expression and prognostic value of serum vitamin D(VitD),fer-ritin(FRT)and heparin-binding epidermal growth factor(HB-EGF)in sepsis patients.Methods 86 sepsis patients who were admitted to the intensive care unit(ICU)of a hospital from January 2021 to January 2022 were selected as the case group,and 60 non-sepsis patients in the ICU were selected as the control group.According to the prognosis of sepsis patients one month later,patients were divided into survival group and death group.Patient's serum upon admission was taken,levels of serum VitD,FRT and HB-EGF were detected,the correlation with the prognosis of sepsis patients was analyzed,and the prognostic value was evaluated by area under curve(AUC)of receiver opera-ting characteristic curve.Results Levels of white blood cell count(WBC),C-reactive protein(CRP),procalcitonin(PCT),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β and FRT of case group were all higher than those of non-sepsis patients in the control group,while the VitD and HB-EGF levels were lower than those of non-sepsis patients in the control group,differences were all statistically significant(all P＜0.05).One month follow-up on the prognosis of sepsis patients showed that 55 patients survived and 31 died.Acute physiology and chronic health evaluationⅡ(APACHE IⅡ)score,sequential organ failure assessment(SOFA)score,PCT,TNF-α,L-1βand FRT score in patients in the death group were all higher than those in patients in the survival group,while VitD and HB-EGF were lower than patients in the survival group,differences were all statistically significant(all P＜0.05).The Pearson correlation analysis results showed that VitD were negatively correlated with APACHE Ⅱ score,SOFA score,WBC,CRP,PCT and TNF-α(all P＜0.05),HB-EGF was negatively correlected with APACHE Ⅱ,score,CRP,PCT,TNF-α,IL-6 and IL-1β(all P＜0.05);while FRT was positively correlated with APACHE Ⅱscores,CRP,PCT,TNF-α,IL-6 and IL-1β(all P＜0.05).The AUC,sensitivity,and specificity of combined de-tection of serum VitD,FRT and HB-EGF in predicting the prognosis of sepsis patients were 0.82(95％CI:0.72-0.86),84.39％,and 69.35％,respectively.Conclusion Serum levels of VitD and HB-EGF are lower and FRT is higher in sepsis patients,their expression levels are closely related to patient prognosis,and have good predictive value for predicting the prognosis of sepsis patients.