Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.

Cancer is a highly deadly disease, with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer being the most prevalent in women. However, traditional cancer treatments present challenges due to their strong toxic side effects and adverse reactions. Numerous studies have demonstrated that natural products derived from various plants possess therapeutic and preventive properties against cancer. These phytochemicals have been extensively investigated as a potential alternative to conventional chemotherapy drugs, owing to their safety and efficacy. This article provides a comprehensive review of the recent advances in the chemoprevention and mechanisms of phytochemicals against the four major female cancers. The focus will be on how these phytochemicals regulate cancer cell proliferation, apoptosis, invasion, and metastasis to impede cancer progression. Given their extensive clinical applications, phytochemicals hold great promise in the field of cancer treatment. It hopes that this review will inspire more researchers to explore the potential of these natural compounds in combating female cancers.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.

Objective:Anterior cruciate ligament injury is the most common type of knee joint ligament injury.Anterior cruciate ligament reconstruction has a high failure rate,with bone tunnel abnormalities as the most significant factor in these failures.Digital orthopedic technology can effectively develop implementation plans for the revision,thus increasing the success rate.This study aims to develop a surgical plan for anterior cruciate ligament revision by employing multiplanar reconstruction(MPR)for measuring bone tunnel position and diameter,and simulating bone tunnel creation via 3D printing preoperatively. Methods:A total of 12 patients who underwent anterior cruciate ligament revision at the Third Xiangya Hospital of Central South University between 2014 and 2021 were retrospectively studied.The data included patient demographics,preoperative formulated knee joint 3D printing models,and preoperative knee CT scans.The study measured the bone tunnel's diameter and position to guide the establishment of revision bone tunnels during surgery,reassessed the postoperative bone tunnels,and evaluated knee joint functional scores[including International Knee Documentation Committee Knee Evaluation Form(IKDC)score,Lysholm score,and Tegner exercise level score]. Results:Preoperative measurements revealed suboptimal femoral tunnels positions in 4 patients and tibial tunnels positions in 2 patients.MPR and 3D printing technology were used to guide the establishment of a new bone canal during surgery,and postoperative measurements were satisfactory for all patients.Preoperative measurements demonstrated the interclass correlation coefficient for femoral tunnels and tibial tunnels diameters were 0.843(P<0.05)and 0.889(P<0.001),respectively.Meanwhile,the intraclass correlation coefficient were 0.811(P<0.05)and 0.784(P<0.05),respectively.The intraoperative diameter of femoral and tibial tunnels showed excellent correlation with postoperative CT measurements,with intraclass correlation coefficient values of 0.995(P<0.001)and 0.987(P<0.001),respectively.All bone tunnel positions were within the normal range.At the final follow-up,knee joint function scores in all 12 patients improved significantly compared to pre-surgery(P<0.001),and the reoperation rate was zero. Conclusion:MPR and 3D printing technology can accurately measure the parameters of reconstructed anterior cruciate ligament bone tunnels.Personalized revision plans for patients with reconstruction failure enhances the success rate of revision surgery and improves patient prognosis.

Objective:To classify the etiology of secondary hemophagocytic syndrome (sHLH) and explore its clinical, laboratory and therapeutic characteristics in order to deepen the understanding of the disease.Method:A retrospective observational study was conducted on sHLH patients who were treated at Peking University People's Hospital from January 2016 to December 2021. Patients under the age of 18 and those with missing clinical data were excluded. The distribution of departments visited and etiologies of sHLH were analyzed. Baseline data, clinical characteristics, complications, laboratory data, treatment, and in-hospital outcomes of sHLH were collected. The sHLH patients were then divided into 3 groups including malignancy group, macrophage activation syndrome (MAS) group and other etiologies (mainly infection) group. Intergroup comparisons were performed using chi-square tests, analysis of variance, Mann-Whitney tests, and other statistical methods.Results:A total 169 patients were enrolled, among these patients, 27.8% were malignancy-related HLH, 47.9% were MAS, and 24.3% were other etiologies related HLH. Statistical analysis revealed that the clinical characteristics of other etiological group was highly consistent with the malignancy group, including more and severer peripheral blood cell reduction, higher sCD25 levels, more Epstein-Barr virus infection, and the prognosis was similar, both were with more than 50% in-hospital mortality. And the incidence of hemophagocytosis was highest in other etiological groups (65.9%). In contrast, MAS group was with an obviously lower mortality of 17.3% ( P<0.05). Meanwhile, treatments including methylprednisolone pulse, cyclosporine A and interleukin-2 were used frequently in MAS group. Conclusion:Malignancy related HLH and other etiologies related HLH exhibit more similar clinical characteristics and prognosis, while the MAS group, has a milder overall condition and better prognosis.

Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).

Objective: To analyze the change trend of HIV genetic subtypes and compare the first CD₄⁺T cell counts of newly diagnosed HIV infected patients in Liuzhou from 1998 to 2012, and provide a reference for AIDS prevention and control. Methods: Newly diagnosed HIV-infected patients from 1998 to 2012 in Liuzhou were selected through national HIV/ADIS comprehensive response information management system. Their plasma samples were used for RNA gene extraction, amplification, sequencing and genotyping. Coharan-Armitage trend test was used to analyze the ratio trend of genetic subtypes and phylogenetic clusters of HIV and Wilcoxon Rank Sum Test was used to compare the first CD₄⁺T cell counts (CD₄) of the different subtype HIV infected patients. Results: A total of 1 877 newly diagnosed HIV infected patients were included in the study. From 1998 to 2012, the proportions of CRF01_AE and CRF01_AE (Cluster 1) increased from 78.4% (76/97) to 91.5% (1 441/1 574), from 63.9% (62/97) to 74.0% (1 164/1 574), and the proportion of CRF07_BC decreased from 17.5% (17/97) to 4.6% (72/1 574), respectively (Z=4.632, P<0.001; Z=2.455, P=0.014; Z=-5.943, P<0.001). The median and interquartile range of the first CD₄ of the patients infected with subtype CRF01_AE (Cluster 1), CRF01_AE (Cluster 2), CRF07_BC and CRF08_BC were 230 (83-375), 215 (48-351), 365 (254-503) and 334 (206-479) cell/μl, respectively. The first CD₄ levels of the patients infected with subtype CRF01_AE (Cluster 1) or CRF01_AE (Cluster 2) were significantly lower than those of CRF07_BC (Z=-4.795, P<0.001; Z=-4.238, P<0.001). Conclusion The genetic subtypes of HIV were mainly CRF01_AE in newly diagnosed HIV-infected patients and this subtype proportion was in increase and the first CD₄ levels of the patients were low in Liuzhou during 1998 to 2012.