Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

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.

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）］

Under the situation of regular epidemic prevention and control of COVID-19, the hospitals need to establish an emergency personnel pool and update it regularly. The author introduced the experience of establishing and managing the emergency personnel pool in a hospital, including the use of information technology to achieve scientific grouping and dynamic management, strengthening the emergency response ability, epidemic prevention and control training and assessment of all staff, ensuring their mental health and logistics support, and improving the performance assessment, salary and welfare system of emergency personnel.From December 2021 to May 2022, the members of the emergency personnel pool completed a total of 62 emergency support tasks. The response time and team gathering time of all emergency tasks were reduced to less than 1 hour. A total of 4 421 medical personnel were sent. The nucleic acid test results of COVID-19 during the tasks were negative, the infection rate was zero, and no adverse events occurred.

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

Numb,one of the important cell fate determinants,plays a key role in regulation of nerve system development,and it is closely related to the occurrence of tumors.It is proven that Numb is implicated in the processes of occurrence,invasion and metastasis of tumors through regulating the way of cell division,cell polarity,epithelial-mesenchymal transitions and several signal pathways,e.g.,Notch,Hh,p53.The expression levels of Numb in cells are related to the malignant degree and prognosis of tumors.It is vital to explore the role of Numb in tumors for treating tumors at the standpoint of Numb.