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.

Aralia taibaiensi, widely distributed in western China, particularly in the Qinba Mountains, has been utilized as a folk medicine for treating diabetes, gastropathy, rheumatism, and cardiovascular diseases. Saponins from A. taibaiensis (sAT) have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion (I/R). However, the underlying mechanisms remain unclear. In vivo, middle cerebral artery occlusion/reperfusion (MCAO/R) induced inflammatory infiltration, neuronal injury, cell apoptosis, mitochondrial dysfunction, and oxidative stress in the ischaemic penumbra, which were effectively mitigated by sAT. sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors (ARs) both in vivo and in vitro. (Ala13)-Apelin-13 (F13A) and small interfering RNA (siRNA) abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/protein kinase B (Akt). Furthermore, sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase (P38 MAPK)/activating transcription factor 4 (ATF4) and upregulating hypoxia-inducible factor-1α (HIF-1α). Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a, thereby suppressing oxidative stress and mitochondrial dysfunction.
Animals ; Reperfusion Injury/prevention & control* ; Aralia/chemistry* ; Saponins/administration & dosage* ; AMP-Activated Protein Kinases/genetics* ; Male ; Apelin/genetics* ; Signal Transduction/drug effects* ; Neuroprotective Agents/administration & dosage* ; Brain Ischemia/genetics* ; Rats, Sprague-Dawley ; Rats ; Oxidative Stress/drug effects* ; Apelin Receptors/genetics* ; Humans ; Apoptosis/drug effects* ; Mice

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.

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 investigate the effects of secukinumab combined with E'xian Huaban decoction on traditional Chinese medicine symptom scores and nailfold microcirculation morphology in patients with plaque psoriasis.Methods A total of 120 patients with plaque psoriasis were selected and randomly divided into monotherapy group(n=60)and combination therapy group(n=60).The monotherapy group received secukinumab treatment,while the combination therapy group was treated with secukinumab plus E'xian Huaban Decoction.Clinical therapeutic efficacy,traditional Chinese medicine symptom scores(including skin lesions,pruritus,rough skin,scales and irritabili-ty),relevant scale[Psoriasisarea and Severity Index(PASI),Dermatology Life Quality Index(DLQI)and Visual Analogue Scale(VAS)]scores,inflammatory factors[interleukin-17(IL-17),interleukin-23(IL-23)and vascular endothelial growth factor(VEGF)]levels and nailfold microcircu-lation morphology(loop tube morphology,blood flow state and loop periphery state)were observed in both groups.Results The overall clinical efficacy rate in the combination therapy group was 95.00％,which was significantly higher than 83.33％ in the monotherapy group(P＜0.05).After treatment,traditional Chinese medicine symptom scores(skin lesions,pruritus,rough skin,scales and irritability),inflammatory factors(IL-17,IL-23 and VEGF)levels,scale(PASI,DLQI and VAS)scores as well as loop tube morphology scores,blood flow state scores and loop periphery state scores were signifi-cantly lower compared to pre-treatment values,and these parameters were significantly lower in the combination therapy group than the monotherapy group(P＜0.05).Conclusion Secukinumab combined with E'xian Huaban Decoction can significantly improve clinical symptoms and signs,and enhancing the clinical therapeutic effect.

Objective To isolate the Japanese encephalitis virus carried by Culex tritaeniorhynchus in Dongchuan District of Yunnan Province and analyze its molecular characteristics, so as to provide insights into the prevention and control of Japanese encephalitis in Yunnan Province. Methods Mosquito specimens were collected using mosquito-trapping lamps from pig farms in Batang Village and Xiaoxin Village, Dongchuan District, Kunming City, Yunnan Province in July 2016, and the mosquito species was identified according to the mosquito morphology. Then, 60 to 100 mosquitoes of each species served as a group and were ground. Baby hamster kidney-21 (BHK-21) cells and Aedes albopictus clone C6/36 cells were used for virus isolation, and positive isolates were identified using flavivirus primers. The positive isolates were amplified using reverse transcription polymerase chain reaction (RT-PCR) assay with 15 pairs of specific primers covering the full length of the genotype I Japanese encephalitis virus, and DNA sequence assembly was performed using the software SeqMan in the DNASTAR package. The obtained sequences were aligned with the complete sequences of 38 Japanese encephalitis virus downloaded from the GenBank with the software MegAlign, and the nucleotide and amino acid homology analyses of the obtained sequences were performed. The difference in amino acid sites was analyzed with the software GeneDoc, and phylogenetic trees were created based on the sequences of the coding region and E protein of the isolated Japanese encephalitis virus with the software Mega X. In addition, the secondary and tertiary structures of the E protein of the Japanese encephalitis virus were predicted using the online tool SOPMA and the software Swiss-Model. Results A total of 5 820 mosquitoes were collected and 3 843 Cx. tritaeniorhynchus (66.03%) were identified according to the mosquito morphology. A positive virus isolate, termed YNDC55-33, was isolated from Cx. tritaeniorhynchoides following batches of virus isolation from mosquito specimens, and cytopathic effect was observed following inoculation into BHK-21 and C6/36 cells. The YNDC55-33 virus isolate was successfully amplified with the flavivirus primes, and a long sequence containing 300 nucleotides was obtained. Following sequence alignment using the BLAST tool, the sequence of the YNDC55-33 virus isolate had high homology with that of the genotype I Japanese encephalitis virus. A long sequence with 10 845 nucleotides in length, which encoded 3 432 amino acids, was obtained by splicing the full sequence of the YNDC55-33 virus isolate. Phylogenetic analysis based on the whole-genome sequence and E gene sequence of the YNDC55-33 virus isolate showed that the new YNDC55-33 virus isolate was most closely related to the genotype I Guizhou isolate (GenBank accession number: HM366552), with nucleotide homology of 98.5% and amino acid homology of 99.4%, and the YNDC55-33 virus isolate shared 97.96% ± 0.33% nucleotide homology and 99.35% ± 0.08% amino acid homology with other genotype I Japanese encephalitis virus isolates, and < 90% nucleotide homology and < 98% amino acid homology with other genotypes of Japanese encephalitis virus. The YNDC55-33 virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate differed at 16 amino acid sites on E gene, and 7 out of 8 key amino acid sites related to neurovirulence. The secondary and tertiary structures of the E protein of the YNDC55-33 virus isolate were predicted to be characterized by random coils. Conclusions A genotype I Japanese encephalitis virus was isolated from Cx. tritaeniorhynchus in Dongchuan District, Kunming City. This virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate does not differ at antigenic epitopes-related key amino acid sites, and the major protein structure of the virus isolate is random coils. This study adds new data for the epidemiological distribution of Japanese encephalitis virus in Yunnan Province, which may provide insights into the prevention and control of Japanese encephalitis in the province.

Abstract Fangjiomics is a promising paradigm that enhances research on multi-omics-based pharmacological mechanisms of Fangji from holistic and systematic perspective. We reviewed recent advances in Fangjiomics, focusing on database and analysis platform development, methodological innovations, and translational applications. Through the integration of Fangji and multi-omics data, multi-level system analysis approaches were developed, encompassing single-target analysis, signaling pathways, multi-targeted network and modules. Fangjiomics has emerged as a key strategy in various areas of Fangji research. To support the high quality development of Fangjiomics, we propose principles and perspectives from the integrated, macro-level, and practical viewpoints.

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.