OBJECTIVE:To investigate the possible mechanism of Artemisia capillaries,and to provide reference for further development and utilization of it. METHODS:The effective components and related target protein of A. capillaries were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) analysis platform database. The effective compound-target protein visual network of A. capillaries was established by using Cytoscape 3.5.1 software,topology analysis was also performed. The protein-protein interaction (PPI) network was constructed and analyzed by STRING database. KEGG pathway enrichment of target protein coding gene was analyzed by DAVID bioinformatics resource database. RESULTS:A total of 13 kinds of effective compounds,189 target proteins and 34 enrichment pathways were selected. Quercetin,β-glutamol,isorhamnetin and artepillin C were main effective compounds. Prostaglandin G/H sythase 2(PTGS 2),heat shock protein 90(HSP 90),dipeptidyl peptidase Ⅳ, protein kinase A catalytic subunit Cα were main target proteins. Transcription factor AP-1 and cell tumor antigen p53 played a key role in PPI network. The target protein coding gene was rich in TNF-α signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,PI3K/Akt signaling pathway,T cell receptor signaling pathway,thyroid hormone signaling pathway, apoptotic signaling pathway,etc. CONCLUSIONS:Quercetin,β-glutamol and isorhamnetin of A. capillaries play an effect on PTGS2,HSP90,transcription factor AP-1 and other target proteins through TNF-α signaling pathway,HIF-1 signaling pathway and PI3K/Akt signaling pathway,so as to play anti-inflammatory and antitumor effect.

BackgroundThe obsessive-compulsive disorder （OCD） features complexity in etiological factors and high heterogeneity in clinical manifestations. OCD patients with different ages of onset vary in clinical symptoms and etiology. However， current studies on inpatients with early- and late-onset OCD are limited. ObjectiveTo explore the differences in clinical characteristics between early- and late-onset OCD inpatients as well as the factors affecting the onset age of OCD， so as to provide references for early screening and treatment of OCD patients. MethodsThis study was based on collected medical records of 540 patients with OCD who received inpatient treatments at the Affiliated Brain Hospital of Nanjing Medical University between March 2012 and March 2023. Patients with onset age above 18 were placed into early-onset group （n=310） and the others into late-onset group （n=230）. Then differences in demographic data and clinical symptoms between two groups of patients were compared. Binary logistic regression was used to analyze the factors that affect the onset age of OCD. ResultsObserving the demographic data， there were significant differences between the two groups in the results in gender， marital status， family history of mental illness， ratio of comorbidities with other mental illnesses， occupational composition， education level and types of obsessive-compulsive symptoms （χ²=22.302、170.556， 9.224， 13.624， 242.277， 59.791， 7.231， P<0.05 or 0.01）. Also， the results in ages of onset and hospitalization between two groups were significantly different （Z=-19.915， 16.831， P<0.01）. In terms of clinical symptoms， the early onset group had a higher proportion of symptoms including obsessive thinking （χ²=11.998， P<0.05）， ordering （χ²=7.731， P<0.05） and rituals （χ²=7.714， P<0.05）， while the proportion of obsessive checking （χ²=8.204， P<0.05） and washing （χ²=7.506， P<0.05） symptoms were relatively low. In terms of risk factors， there were several independent risk factors that influence the onset age of OCD inpatients， including comorbid neurodevelopmental disorder， comorbid affective disorder， family history of schizophrenia and family history of affective disorder （OR=19.587， 1.830， 3.065， 4.431， P<0.05）. Among them， comorbid neurodevelopmental disorder was the core influencing factor， and female gender was a protective factor for early-onset patients （OR=0.417， P<0.01）. ConclusionThere are differences in demographic data and clinical symptom characteristics between early- and late-onset OCD inpatients， and comorbid neurodevelopmental disorder plays as a core risk factor affecting the onset age of OCD inpatients. ［Funded by Jiangsu Province Key Research and Development Plan for Social Development Special Project（number， BE2021616） ； Jiangsu Province Social Development General Project （number， BE2022678）； Key Project of Nanjing Medical Science and Technology Development Fund （number， ZKX20029）］

Objective To compare differences in mechanical stability of intramedullary fibular allograft with cannulated screw (modified method) and cannulated screw alone (conventional method) for fixing young and middle-aged Pauwels Ⅰ, Ⅱ, Ⅲ femoral neck fractures. Methods Models of Pauwels Ⅰ, Ⅱ, Ⅲ femoral neck fracture fixed by conventional method and modified method were constructed. Stress distributions on weight-bearing area of the femoral cortical bone shell and the end of femoral neck fracture, as well as shear stress distributions on cortical bone shell of the femoral head and femoral neck fracture surface were analyzed, the maximum principal strain cloud maps of the femur in coronal position were drawn according to the predicted data, and the displacements of femoral neck fracture end between two groups were compared. Results The shear stress distributions on cortical bone shell of the femoral head in two directions (S12, S13) showed that femoral neck fractures fixed by modified method was superior or close to that by conventional method. Besides, the shear stress distributions on fracture surface of the femoral neck in two directions (S12, S23) showed that modified internal fixation was superior to conventional internal fixation. The displacements of femoral neck fracture end in Pauwels Ⅱ and Ⅲ fracture fixed by conventional method were greater than those by modified method and the displacements of Pauwels Ⅱ fracture fixed by conventional method were obviously larger than those of Pauwels Ⅱ fracture fixed by modified method. But Pauwels Ⅰ fracture fixed by modified method showed a larger displacement than that fixed by conventional method. Conclusions Modified method is more suitable for fixing femoral neck fracture with large angles (Pauwels Ⅱ and Ⅲ fracture), and conventional method is more suitable for fixing neck fracture with small angles (Pauwels Ⅰ fracture).

Objective To investigate the regulatory effect of Jianpi Huayu Prescription(Ginseng Radix et Rhizoma,Poria,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on epithelial-mesenchymal transition(EMT)and angiogenesis of hepatocellular carcinoma through TGF-β1/Smad7 pathway.Methods(1)Hep3B tumor-bearing mouse model was established by BALB/C-nu nude mice.The mice were randomly divided into control group and Jianpi Huayu Prescription low-,medium-and high-dose groups(3.844,7.689,15.378 g·kg-1·d-1),with five mice in each group.Intragastric administration was performed once a day for 21 days.(2)Hep3B cells were divided into blank group,model group(10 ng·mL-1 TGF-β1),low-concentration group(10 ng·mL-1 TGF-β1+4 mg·mL-1 Jianpi Huayu Prescription),and high-concentration group(10 ng·mL-1 TGF-β1+6 mg·mL-1 Jianpi Huayu Prescription).After 48 hours of TGF-β1 induction,the cells were replaced with the corresponding concentration of Jianpi Huayu Prescription complete culture medium(0,4,6 mg·mL-1)and cultured for 24 hours.(3)HUVEC cells were divided into normal group,model group,Chinese medicine group,model plus Chinese medicine group.The cells in the normal group were cultured with conditioned medium without TGF-β1;the cells in the model group were cultured with conditioned medium containing TGF-β1.The cells in the Chinese medicine group were cultured in conditioned medium containing 4 mg·mL-1 Jianpi Huayu Prescription without TGF-β 1.The cells in the model plus Chinese medicine group were cultured with conditioned medium containing 4 mg·mL-1 Jianpi Huayu Prescription and TGF-β1.After 24 hours of continuous culture,the cells were collected for subsequent experiments.(4)The tumor mass index and tumor inhibition rate of subcutaneous transplantation tumor of Hep3B tumor-bearing nude mice were calculated.The expression of CD31 in subcutaneous xenografts of tumor-bearing nude mice was detected by immunofluorescence.The microvessel density of subcutaneous transplanted tumor in nude mice was detected by immunohistochemistry.The migration ability of Hep3B cells was detected by cell scratch test.Transwell assay was used to detect the invasion ability of Hep3B/HUVEC cells.The tube formation ability of HUVEC cells was detected.The expression levels of related proteins in subcutaneous transplanted tumors,Hep3B and HUVEC cells of tumor-bearing nude mice were detected by Western Blot.Results(1)Compared with the control group,the weight and tumor mass index of subcutaneous transplanted tumor in nude mice in the medium-and high-dose groups of Jianpi Huayu Prescription were significantly decreased(P＜0.01).The expression of CD31 and microvessel density in subcutaneous transplanted tumors of nude mice in low-,medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01),the protein expressions of VE-cadherin,EphA2 and N-cadherin were significantly down-regulated(P＜0.05,P＜0.01),and the protein expressions of E-cadherin and Smad7 was significantly up-regulated(P＜0.01).(2)Compared with the blank group,the relative migration rate of Hep3B cells in the model group was significantly increased(P＜0.05),and the number of invasive cells was significantly increased(P＜0.01).The protein expressions of Vimentin and N-cadherin were significantly up-regulated(P＜0.01),and the protein expressions of E-cadherin and Smad7 was significantly down-regulated(P＜0.01).Compared with the model group,the relative migration rate of Hep3B cells in the low-and high-concentration groups of Jianpi Huayu Prescription was significantly decreased(P＜0.01),and the number of invasive cells was significantly decreased(P＜0.01).The protein expressions of Vimentin and N-cadherin was significantly down-regulated(P＜0.01),and the protein expressions of E-cadherin and Smad7 were significantly up-regulated(P＜0.01).(3)Compared with the normal group,the number of tubular branching points formed by HUVEC cells in the model group was significantly increased(P＜0.01),the length of tubular branching was significantly increased(P＜0.01),and the number of invasive cells was significantly increased(P＜0.01).The protein expressions of VE-cadherin and EphA2 were significantly up-regulated(P＜0.01),and the protein expression of Smad7 was significantly down-regulated(P＜0.01).Compared with the model group,the number of tubular branching points formed by HUVEC cells in the model plus Chinese medicine group was significantly reduced(P＜0.01),the length of tubular branching was significantly shortened(P＜0.01),and the number of invasive cells was significantly reduced(P＜0.01).The protein expressions of VE-cadherin and EphA2 were significantly down-regulated(P＜0.01),and the protein expression of Smad7 was significantly up-regulated(P＜0.01).Conclusion Jianpi Huayu Prescription can significantly inhibit the growth,invasion and migration of hepatocellular carcinoma,which may be related to the regulation of EMT and angiogenesis mediated by TGF-β1/Smad7 pathway.

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity