Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To investigate the predictive value of serum ferritin(SF)in early gestation,pre-pregnancy body mass index(BMI)and gestational age for gestational diabetes mellitus(GDM).Methods A total of 260 pregnant women who had a routine prenatal examination in Wenzhou People's Hospital were collected from January 2021 to December 2022.Fasting venous blood was collected at the first prenatal examination(within 14 weeks'gestation)for SF.According to the results of 75 grams oral glucose tolerance test(OGTT)between 24 weeks and 28 weeks,they were divided into GDM group(n=62)and normal glucose tolerance(NGT)group(n=198).The general clinical data of the two groups were compared;Multivariate Logistic regression analysis was conducted to determine the independent risk factors of GDM.Receiver operating characteristic(ROC)curve was used to further analyze the predictive value of SF in early gestation,pre-pregnancy BMI and gestational age for GDM.Results Pregnant women in GDM group had higher SF,BMI and gestational age in early pregnancy than those of NGT group(P<0.05).Pre-pregnancy BMI,gestational age and SF increased in early pregnancy were independent risk factors for GDM(P<0.05).The area under the curve(AUC)of SF in early pregnancy as well as pre-pregnancy BMI and gestational age for predicting GDM were 0.612,0.691 and 0.664.The best tangent point values were 94.045ng/ml,21.125kg/m2 and 28.500 years old,respectively.The total AUC of ROC predicted GDM by SF in early gestation,pre-pregnancy BMI and gestational age was 0.750,the sensitivity and specificity were 66.1%and 79.3%,respectively.Conclusion SF in early gestation,pre-pregnancy BMI and gestational age are important factors in the development of GDM,the combined detection of SF in early pregnancy,pre-pregnancy BMI and gestational age has a certain predictive value for GDM.

Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.

From November 2020 to November 2021, the TEST(Task-Experience- Supervise-Thinking) teaching model was adopted for general practice residency training in teaching clinic of Changfeng Health Service Center of Shanghai Putuo district. The satisfaction of mentors, residents and patients was surveyed with self-assessment questionnaire. The satisfaction scores of mentors, residents and patients were (79.89±0.40), (79.96±0.19) and (49.92±0.40). The adaption of model TEST in teaching clinic is more effective in training of clinical competency, communication ability, management ability and narrative ability for general practice residents. It is also beneficial for mentors to upgrade their teaching ability, as well as for patients to improve their experience and satisfaction for seeking medical service. It is worth popularizing in the community practice base of general resident training.

ObjectiveTo investigate the detoxification mechanism of Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta， and their effective components ellagic acid， liquiritin and aconitine based on cardiac cytochrome P450 （CYP450） system. MethodIn in vivo experiments， rats were randomly divided into control group， prepared Aconiti Kusnezoffii Radix Cocta group （0.25 g·kg^-1）， Chebulae Fructus group （0.252 g·kg^-1）， Glycyrrhizae Radix et Rhizoma group （0.25 g·kg^-1） and combination group （0.25 g·kg^-1 Chebulae Fructus+0.25 g·kg^-1 Glycyrrhizae Radix et Rhizoma+0.25 g·kg^-1 prepared Aconiti Kusnezoffii Radix Cocta， with prepared Aconiti Kusnezoffii Radix Cocta as standard）. After 8 days of administration， creatine kinase （CK） and lactate dehydrogenase （LDH） in rats were detected to observe the pathological changes of heart tissue. Real-time PCR and Western blot were performed to detect the mRNA and protein expressions of CYP2J3， respectively. In in vitro experiments， control group， aconitine group， ellagic acid group， liquiritin group and combination group （aconitine+ellagic acid+liquiritin） were set， and their effects on cell number， DNA content， reactive oxygen species （ROS） and mitochondrial membrane potential （MMP） were detected by high content analysis. The changes in the mRNA and protein expressions of CYP2J3 were also observed. ResultIn vivo experiments， compared with the control group， the prepared Aconiti Kusnezoffii Radix Cocta group had increased CK and LDH in serum （P<0.05， P<0.01）， while the combination group had decreased activities of CK and LDH. Additionally， pathological staining results showed that Chebulae Fructus and Glycyrrhizae Radix et Rhizoma reduced the cardiac toxicity caused by prepared Aconiti Kusnezoffii Radix Cocta. Real-time PCR found that compared with the control group， prepared Aconiti Kusnezoffii Radix Cocta down-regulated the mRNA level of CYP2J3 （P<0.05）， while up-regulated that expression when used in combination with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma （P<0.01）. The protein and mRNA translation levels were basically consistent. In vitro experiments， high content analysis revealed that there was a decrease in the cell number， DNA content and MMP fluorescence value of the aconitine group （P<0.01） and the combination group （P<0.05， P<0.01）， and the fluorescence value of the combination group was higher than that of the aconitine group. Moreover， aconitine down-regulated the mRNA level of CYP2J3 （P<0.05）， but the down-regulating ability of aconitine was reversed in the combination group （P<0.05）. ConclusionThe detoxification mechanism of combined Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and prepared Aconiti Kusnezoffii Radix Cocta is mainly that the combination of ellagic acid， liquiritin and aconitine can up-regulate the expression of CYP2J3， and promote the metabolism of arachidonic acid （AA） to produce epoxyeicosatrienoic acids （EETs）， thus reducing the cardiac toxicity， and this effect may start from the transcriptional link.

Objective:To retrieve relevant evidence on exercise assessment and exercise training for children with congenital heart disease at home and abroad, and to summarize the best evidence to provide reference for clinical medical staff.Methods:UpToDate, National Guidelines Clearinghouse (NGC), Registered Nurses Association of Ontario (RNAO), Scottish Intercollegiate Guidelines Network (SIGN), National Institute for Health and Care Excellence (NICE), BMJ Best Practice, American Heart Association (AHA), Cochrane Library, Joanna Briggs Institute(JBI) Evidence-Based Health Care Center Database, PubMed, CINAHL, China Biomedical Literature Database, Yimaitong, Wangfang Database, CNKI were searched, related evidence on exercise assessment and exercise training for children with congenital heart disease. The search period was from the establishment of the database to March 2021. Clinical decision-making and recommended practice used retrospective evaluation methods for quality evaluation; guidelines used the 2012 version of the clinical guideline research and evaluation system (AGREE Ⅱ) for evaluation; systematic reviews used the systematic evaluation tool (AMSTAR) for evaluation; expert consensus used JBI (2016 version) evaluate the authenticity evaluation tools of opinions and consensus articles. Two researchers independently evaluated the literature, combined with the judgment of professionals, and extracted the literature data that met the standards.Results:A total of 15 documents were included, including 2 clinical decisions, 4 guidelines, 1 recommended practice, 5 systematic reviews, 3 expert consensus, and 22 best evidences. Including related personnel, exercise evaluation, exercise monitoring, exercise classification, exercise training, and exercise follow-up.Conclusions:This study summarizes the best evidence of exercise assessment and exercise training for children with congenital heart disease, and provides evidence-based evidence for clinical practice. It is recommended that children with congenital heart disease undergo exercise assessment and formulate a personalized exercise training program to promote the transformation of the best evidence into clinical practice.

Objective:To explore the effect of family doctor-specialist dual-contract service model on the management of type 2 diabetic patients in the community.Methods:Two hundred patients with type 2 diabetes mellitus (T2DM)who were treated in Changfeng Community Health Service Center between February 2019 and January 2021 were selected as the study objects by cluster sampling method. Patients were randomly divided into study group and control group with 100 cases in each group. The control group was managed with the conventional family doctor contract service, and the study group was managed with the family doctor-specialist double contract service. After one year of management, the fasting blood glucose, 2 h-postprandial blood glucose, glycosylated hemoglobin, diet control, blood glucose monitoring, medication compliance, exercise and other health behaviors, quality of life and satisfaction of patients were compared between two groups.Results:After intervention, fasting blood glucose, 2 h-postprandial blood glucose and glycosylated hemoglobin in the study group were significantly lower than those in the control group ( t=10.29, 8.49, 7.99, all P<0.05); the health related behaviors such as diet control, exercise behavior, blood glucose monitoring, and medication compliance in the study group were significantly better than those in the control group ( t=9.78, 6.72, 39.81, 7.88, all P<0.05); the quality of life in patients of study group was higher than that of the control group ( P<0.05); the satisfaction rate in study group was higher than that of control group (90.0% vs. 69.0%, χ 2=6.39, P=0.031). Conclusion:Compared with conventional family contract service model, the double contract service improves patient self-management, helps to reduce the blood glucose level and gains high patients′ satisfaction, which is worth promoting and applying in the management of type 2 diabetic patients in the community.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Objective To investigate the clinical study on drynaria injection for delayed healing of fracture patients.Methods 108 patients with fracture delayed union from February 2010 to February 2016 in our hospital were selected and randomly divided into the control group and the experiment group by different treatment,54 cases in each group.The control group were treated by conventional therapy,the experiment group were treated with drynaria rhizome injection on the bases of control group.The total effective rate,serum alkaline phosphatase,NGF and BMP-2 levels were observed and compared after treatment.Results After treatment,the total effective rate of experiment group was higher than control group (P<0.05);After treatment for 7 and 14 days,the serum alkaline phosphatase level of the two groups were significantly increased (P<0.05),and compared with the control group, the serum alkaline phosphatase content of the experimental group was higher (P<0.05);After treatment for 7 and 14 days,the serum NGF and BMP-2 levels of two groups were significantly increased(P<0.05),and compared with the control group,the experimental group was higher than those in the control group.Conclusion Injection of rhizoma drynariae in the treatment of delayed healing of patients with significant effect,increase the levels of serum alkaline phosphatase, serum NGF and BMP-2,promote fracture healing in patients and improve clinical efficacy.