AIM: To provide references for the non-clinical evaluation of therapeutic targets or drugs for retinoblastoma, fluorescently labeled Y79 cells are injected into the vitreous body of BALB/c-nu mice to establish a retinoblastoma model, and the Melphalan treatment group is used as a positive control, which is verified by fluorescence imaging technology.METHODS: BALB/c-nu mice were intravitreous injected with GFP transfected Y79 cells(1.0×107 cell/mL, 3 μL)to establish the model. On the 27th day, the mice were randomly divided into model control group and different doses of Melphalan groups(1, 3, 10 μg/eye groups)according to the fluorescence value of in vivo imaging, with vitreous body single administrated and ocular symptoms observed daily. Slit-lamp examination was performed at 12, 20, 29, 35, 42, 48, 55, 76, and 83 d after modeling. In vivo imaging was performed on 12, 20, 27, 41, 48, 55, 62, 69, 76, and 83 d. At the last treatment, the eyeball, brain and cerebellum tissues were removed for histopathological examination.RESULTS: From the sixth day of modeling, cloud-like substances could be seen in the eyes of the animals, and the cloud-like substances occupied the whole eyeball of the mice in the model control group at the later stage, accompanied by irregular growth of blood vessels. After 27 days of modeling, the fluorescence value was detected in all the animals, and the fluorescence value continued to increase with the extension of modeling time. The fluorescence value of the tumor reached the peak after 69-83 days of modeling. Histological examination showed severe proliferation of intraocular tumor cells in the model control group, and tumor cells were observed in the brain of 1 model animal. In the 10 μg/eye Melphalan group, the fluorescence value was significantly decreased at 17 d after administration. The fluorescence value of the 3 μg/eye Melphalan group was significantly inhibited at 59 d after administration. No tumor cells were found in the brain tissue of animals in all Melphalan groups.CONCLUSION: After vitreous injection of Y79/pCDH-LUC-copGFP cells in BALB/c-nu mice, significant ocular lesions and proliferation of tumor cells were observed in the eyes. Meanwhile, Melphalan intervention significantly inhibited tumor cells in a dose-dependent manner, indicating that the mouse model of retinoblastoma was successfully constructed.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Forsythiae fructus,a traditional Chinese medicine for heat clearing and detoxifying,is commonly used in clinic.It mainly contains phenylethanol glycosides,lignans,terpenoids,volatile oils,flavonoids and other chemical components.Numerous studies have confirmed that forsythiae fructus has anti-inflammatory,antibacterial,antiviral,anti-cancer and other pharmacological effects.Moreover,it has high safety.In this paper,the chemical composition,pharmacological action and safety of forsythiae fructus were reviewed.The aim of this study is to collect the relevant research achievements of forsythiae fructus,and to provide ideas and references for its further research and clinical application.

ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials （RCT） of traditional Chinese medicine （TCM） for treating chronic atrophic gastritis （CAG）， so as to provide references for constructing the core outcome set （COS） of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated， and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included， with a sample size of 44-398 cases. 164 outcome indicators were reported， with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes， followed by physical and chemical examination （69.41%）， TCM syndrome （12.69%）， symptoms and signs （11.15%）， safety indicators （5.37%）， quality of life （0.65%）， long-term prognosis （0.65%）， and economic evaluation （0.08%）. According to the statistical analysis， there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG， including various indicators， non-standard name reports， unclear primary and secondary indicators， random combination of subjective and objective indicators， neglected patient report outcome indicators， missing long-term prognosis and economic indicators， insufficient reporting of safety indicators， and inconsistent measurement tools and measurement time points. ConclusionIn the past five years， there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.

Objective To observe the efficacy and side effects of anlotinib combined with paclitaxel and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Methods We retrospectively analyzed 50 cases of advanced esophageal squamous cell carcinoma diagnosed pathologically. Among them, 24 cases were treated with the combination of anlotinib and paclitaxel plus cisplatin (experimental group), and 26 cases were treated with paclitaxel plus cisplatin regimen (control group). The efficacy and adverse reactions were observed and followed up. Results The objective response rates of the experimental and control groups were 83.33% and 53.84% (P < 0.05), the disease control rates were 100% and 96.15% (P > 0.05), mPFS were 10.6 and 9.13 months (P < 0.05), and mOS were 13.4 and 11.8 months (P < 0.05). The common adverse events in the experimental group were hand-foot syndrome (12.5%), hypertension (12.5%), epistaxis (8.33%) and proteinuria (4.16%), all of which were grade Ⅰ-Ⅱ and controllable without affecting the continuity of chemotherapy. Conclusion The combination of anlotinib, paclitaxel and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma can improve the curative effect and the adverse effects are endurable.

Objective:To explore the application effect of nursing based on transtheoretical model in patients with oral surgery.Methods:A total of 120 patients with oral surgery who were admitted to Department of Stomatology of the First Affiliated Hospital of Xinxiang Medical University from October 2019 to January 2020 were selected as research objects by the convenient sampling method. According to random number table, they were divided into the control group and the observation group, with 60 cases in each group. Patients in the control group were given routine nursing while patients in the observation group were given transtheoretical model-based nursing at basis of the control group. The amount of dental plaque, comfort of oral cavity, score of psychological state and degree of oral cleanliness before and after nursing were compared between the two groups.Results:After intervention, the amount of dental plaque and the score of oral comfort in the observation group were lower than those in the control group, and the differences were statistically significant ( P<0.05) . After intervention, SAS and SDS scores in the observation group were lower than those in the control group, and the differences were statistically significant ( P<0.05) . The degree of oral cleanliness of the observation group was better than that of the control group after intervention, and the difference was statistically significant ( P<0.05) . Conclusions:Nursing based on transtheoretical model can effectively reduce postoperative amount of oral plaque of patients with oral surgery, improve comfort of oral cavity and oral cleanliness and correct bad mood of patients, which is worthy of clinical application.

Fragile X syndrome (FXS) is the most common monogenic disease that causes intellectual disability and autism spectrum disorder (ASD),causing moderate to severe mental retardation with unusual facial features and connective tissue abnormalities.Fragile X syndrome is caused by the mutation of FMR1 gene,resulting in the reduction or loss of its product,fragile X mental retardation protein (FMRP).The diagnosis is mainly based on the detection of FMR1 gene,and there is no effective treatment for fragile X syndrome.Therefore,it is very important to strengthen genetic counseling and prenatal diagnosis,and effectively reduce the incidence of fragile X syndrome.