ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.

Objective:To investigate the rate-limiting steps of hand-assisted laparoscopic donor nephrectomy, analyze the relevant factors affecting surgical difficulty, and subsequently construct a mathematical model to predict the difficulty of the procedure preoperatively.Methods:A retrospective study was conducted on 100 kidney donors who underwent hand-assisted laparoscopic donor nephrectomy performed by the same surgeon at Beijing Friendship Hospital, Capital Medical University from January 2021 to January 2024. Preoperative demographic data, imaging findings, general condition, donor kidney size, and postoperative complications were collected and analyzed. The surgeon′s subjective rating (1-3 points) was used as a quantitative measure of surgical difficulty. ANOVA and Chi-square tests were employed to explore the differences in postoperative complications, recovery, operative time, and intraoperative blood loss among groups with varying levels of difficulty. The main procedure was divided into four steps (excluding abdominal closure): Trocar placement, renal hilar dissection, perinephric dissection, and kidney retrieval. The time for each step and the total operative time were recorded. Pearson correlation test was used to analyze the relationship between each step and the total operative time, and ANOVA test was used to assess the time differences between steps and to determine if the time for the same step varied across different difficulty subgroups, thereby identifying the rate-limiting step of hand-assisted laparoscopic donor nephrectomy. In terms of the risk factors influencing the difficulty of surgery, Pearson and Spearman correlation tests were used to investigate the relationship between preoperative donor data and surgical difficulty scores, and a predictive model was constructed using multiple linear regression. Finally, the model was internally and externally validated to confirm its accuracy and effectiveness.Results:As the surgical difficulty increased (groups 1, 2, and 3), the postoperative drainage tube duration was correspondingly prolonged [(5.92±1.48) d, (8.00±1.75) d, and (11.88±4.45) d, respectively, P<0.05], and the severity of postoperative complications also significantly increased (the incidence of Clavien-Dindo grade ≥2 was 5.66%, 31.82% and 64.00%, respectively, P<0.01). In the analysis of rate-limiting steps, the time taken for all steps, except for Trocar placement, showed significant differences among the difficulty subgroups ( P<0.001). However, the average time for renal hilar dissection was (19.82±5.65) min, which was significantly longer than the other steps ( P<0.001). Therefore, renal hilar dissection was identified as the rate-limiting step of hand-assisted laparoscopic donor nephrectomy. In terms of the influencing factors of surgical difficulty, donor obesity, kidney width, abdominal anteroposterior sagittal diameter, number of renal arteries, distance from renal artery bifurcation to the abdominal aorta, degree of renal artery calcification, and mayo adhesive probability (MAP) score were all correlated with the surgical difficulty score ( P<0.05). However, multiple linear regression analysis revealed that only the number of renal arteries and the MAP score were the independent risk factors for higher surgical difficulty of hand-assisted laparoscopic donor nephrectomy. The predictive equation was: surgical difficulty=0.649×number of renal arteries+ 0.770×MAP score. Both internal and external validation confirmed the model's good accuracy. Conclusions:This study established a reliable and objective predictive model for the difficulty of hand-assisted laparoscopic donor nephrectomy based on the number of renal arteries and the MAP score. Renal hilar dissection was identified as the rate-limiting step of the procedure. This provides a reference for selecting an appropriate surgeon based on the predicted surgical difficulty.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Objective To systematically characterizes the temporal changes in urokinase-type plasminogen activator(uPA)over the course of neoplastic progression using a mouse oral squamous cell carcinoma(OSCC)model induced by 4-nitroquinoline-1-oxide(4-NQO).Methods A total of 65 wild-type C57BL/6 mice of 5 weeks old were randomly assigned to two groups,a 4-NQO group(n=50),which received daily administration of 100 μg/mL 4-NQO in drinking water,and a control group(n=15),which received sterile water.At 12,16,20,22,and 24 weeks,10 mice from the 4-NQO group and 3 from the control group were randomly selected,weighed,and sacrificed.Tongue tissues were collected for hematoxylin-eosin(HE)staining to preliminarily assess OSCC development,and for immunofluorescence staining and quantitative real-time PCR to evaluate dynamic uPA expression in tongue tissues during OSCC progression.Results After 16 weeks of exposure,4-NQO-treated mice exhibited significantly lower body mass compared with that of the controls(P<0.05)and the weight loss became increasingly more pronounced over time.Histopathological changes in tongue tissues progressed in a clearly time-dependent manner—hyperplasia and mild dysplasia emerged at week 12,while moderate-to-severe dysplasia and carcinoma were observed by week 22,yielding a tumorigenic rate of 25%,which escalated to 70%by week 24.Immunofluorescence and qPCR analyses demonstrated a pronounced,progressive up-regulation of uPA expression in lesional tissues as OSCC progressed(P<0.000 1).Conclusion This study not only confirmed the uniqueness of the 4-NQO model in OSCC research,but also revealed the changes in uPA during tumor invasion.These findings provide a theoretical foundation for the development of early diagnosis and precision treatment strategies,holding significant potential clinical value and research importance for improving patient prognosis.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Objective To analyze the influencing factors of unplanned extubation(UE)occurrence of peripherally inserted central catheter(PICC)in the patients with hematological diseases.Methods A retro-spective cohort study method was adopted.The data of 7 298 patients with hematological diseases implanted with PICC catheter and followed up to its removal from January 1,2016 to December 31,2020 in the Hematol-ogy Hospital of Chinese Academy of Medical Sciences were collected,including the demographic information,catheterization records,maintenance and extubation records.According to whether UE occurring,they were divided into the UE group(n=262)and normal extubation group(n=7 036).The general data were com-pared between the two groups.The COX regression was used to analyze the influencing factors of UE in pa-tients with hematological diseases.The dose-effect relationship between age and PICC UE occurrence risk was studied by the restrictive cubic spline method.Results The incidence rate of UE was 3.6％(262/7 298).The COX regression analysis results showed that the gender,disease diagnosis,fibrinogen,prothrombin time,PLT,catheter material,number of punctures during catheterization,positioning method of catheter tip,num-ber of catheter-related complications occurrence were related to PICC UE occurrence in the patients with he-matological diseases(P＜0.05).The results of restricted cubic spline showed that there was a"U"-type non-linear relationship between age and UE risk(X2=17.710,P＜0.05),and the risk of UE was the lowest when the age was 30 years old.Conclusion In PICC,the emphasis should be paid to the male patients with hemato-logical malignancies who have repeated punctures during catheterization,no intracardiac electrocardiographic positioning during catheterization,bleeding tendency,indwelling polyurethane catheters and repeated catheter-related complications in order to decrease the UC occurrence probability.

Objective:To investigate the effect of visceral fat thickness before operation on the operative difficulty and postoperative complications in renal transplantation recipients.Methods:A total of 179 patients diagnosed with end-stage renal disease who underwent kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2020 to January 2022 were retrospectively included. According to the visceral fat thickness measured by CT before transplantation (distance from anterior wall of abdominal aorta to parietal peritoneum at 1 cm above umbilicus), patients were divided into two groups, with 103 patients in thin visceral fat group with visceral fat thickness ≤7.5 cm and 76 patients in thick visceral fat group with visceral fat thickness>7.5 cm. The epidemiological data before renal transplantation, operative time, intraoperative blood loss, postoperative complications, renal function after transplantation and patients′ recovery state were analyzed and compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups. The Chi-square test was used to compare the count data. Results:The mean age and body mass index of patients in thin visceral fat group [(38.70±11.50) years and (21.28±2.93) kg/m 2] were lower than those in thick visceral fat group [(43.14±11.42) years and (24.78±3.37) kg/m 2], and the differences were statistically significant ( P< 0.05). There was no significant difference in other preoperative epidemiological data between the two groups ( P>0.05). In terms of operation difficulty, the mean operation time of thin visceral fat group was (117.16±34.33) min, which was significantly shorter than that of thick visceral fat group (137.11±20.02) min. The mean intraoperative blood loss in the thin visceral fat group was (89.12±45.95) mL, which was lower than that in the thick visceral fat group (125.39±54.88) mL, the differences were statistically significant ( P<0.001). In terms of postoperative complications, 41 patients in the thin visceral fat group had postoperative infection, incision pain and intraoperative effusion, and the incidence was 39.8% (41/103), which was significantly lower than that in the thick visceral fat group (78.9%, 60/76), the difference was statistically significant ( P<0.001); However, there was no significant difference in the incidence of Clavien-Dindo grade 3 or higher complications between the two groups ( P> 0.05). There was no significant difference in serum creatinine levels at 3, 5, 7 days and 1, 2 months after surgery among patients with different visceral fat thickness ( P> 0.05). However, the mean serum creatinine level in the thin visceral fat group was (116.06±36.45) μmol/L, which was lower than that in the thick visceral fat group (133.35±72.26) μmol/L, and the difference was statistically significant ( P=0.038). There was no significant difference in the incidence of delayed renal function recovery between the two groups ( P> 0.05). At the same time, there was no significant difference in postoperative drainage tube indwelling time and hospital stay between the two groups ( P> 0.05). Conclusions:The thicker visceral fat in end-stage renal disease patients before transplantation, the higher the incidence of general postoperative complications, but the severity of complications, patients′ recovery after transplantation and the short-term function of the transplanted kidney are not significantly related to the thickness of visceral fat in the recipients. Meanwhile, although the visceral fat thickness of the recipients in this study was correlated with serum creatinine levels at 3 months after transplantation, its correlation with long-term graft renal function and graft survival time remains to be further studied.

Objective To identify the influencing factors of operation time of hand-assisted laparoscopic living donor nephrectomy, and to analyze the relationship between influencing factors and the severity of postoperative complications. Methods Clinical data of 91 donors who underwent hand-assisted laparoscopic nephrectomy were retrospectively analyzed. The correlation between preoperative baseline data of donors and operation time was analyzed. The relationship between operation time and postoperative complications was assessed and the threshold of operation time was determined. Results Multiple donor renal arteries, thick perirenal and posterior renal fat, metabolic syndrome, high Mayo adhesive probability (MAP) score and Clavien-Dindo score prolonged the operation time. By analyzing the receiver operating characteristic (ROC) curve, we found that when the operation time was ≥138 min, the incidence of postoperative complications of donors was significantly increased (P<0.05). Conclusions For donors with multiple renal arteries, thick perirenal and posterior renal fat, metabolic syndrome and high MAP score and Clavien-Dindo score, experienced surgeons should be selected to make adequate preoperative preparation and pay close attention after surgery, so as to timely detect postoperative complications and reduce the severity of complications, enhance clinical prognosis of the donors.