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.

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg^-1） group， a rapamycin （RAPA， 2 mg·kg^-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg^-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger

Objective To explore the current situation,research hotspots and future development direction of medical community in our country.This paper puts forward some suggestions for the future development of medical community in our country,and provides the research reference.Methods A total of 1 329 articles on medical community published by CNKI from February 2016 to July 2016 were 2023 by NoteExpress and CiteSpace,from the point of view of medical service homogeneity,this paper analyzes the general situation,research hotspots and research trends of the medical community domain literature,this paper reviews the research from the perspectives of medical expense payment,medical personnel training and health file management.Results The research topics of the medical community are gradually diversified and characterized,the research methods of the medical community are diversified,and the research perspectives of the medical community are differentiated.Conclusion Fu-ture research should focus on the following aspects:the scope of medical community research topics,health records management,government support system,medical integration in the post-epidemic era.

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.

Intravenous thrombolysis is one of the most effective methods for the treatment of acute cerebral infarction.However,secondary hemorrhagic transformation after thrombolysis is a serious complication.Many studies have shown that hypofibrinemia and severe damage to the blood-brain barrier are important causes of this result.Bleeding after thrombolysis is not caused by a single factor.Foreign countries have more predictive research models for hemorrhagic transformation.Various research results have their own advantages and disadvantage.Domestic research is still scarce.This article reviews the pathogenesis,classification and prediction models of hemorrhagic transformation after intravenous thrombolysis.

Objective This study aims to explore the risk factors of hemorrhagic transformation (HT),and compare the predictive ability of different predictive models.Methods Retrospective analysis of clinical data of patients with intravenous thrombolysis in our hospital from June 2015 to June 2018.The risk factors were statistically analyzed.The results were fitted into a new predictive model named MODEL.The area under receiver operating characteristic (ROC) curve was used to compare the predictive ability of the MODEL and some traditional methods including the Multicenter Stroke Survey (MSS),and the Totaled Health Risks In Vascular Events Score (THRIVE),and the Glucose at presentation,Race,Age,Sex,systolic blood Pressure at presentation,Severity of stroke at presentation (GRASPS) to HT.Results The results of single factor analysis showed that there were significant differences in the history of hypertension,the history of atrial fibrillation,the systolic pressure before thrombolysis,the National Institute of Health Stroke Scale (NIHSS) score before thrombolysis,the level of plasma total cholesterol (TG),low density lipoprotein cholesterol (LDL-C),apolipoprotein B (Apo B),D dimer (DD),and the platelet distribution width and the sodium ion.Multivariate logistic regression analysis confirmed that the NIHSS score before thrombolysis,the level of plasma LDL-C and DD were independent risk factors for HT.The formation of a new predictive model was logi(p) =0.21 +0.99 × NIHSSscore-0.834 × LDL-C +0.002 × DD,which was defined as predictive mode of MODEL.The four predictive models all had predictive effects on HT.Z test results showed that,compared with the GRASPS,the MODEL and MSS showed a higher predictive power.Conclusions The NIHSS score before thrombolysis,and the level of plasma LDL-C,and DD were independent risk factors for HT after intravenous thrombolysis.MODEL and MSS had better predictive performance.

Objective To explore the effects of steering group model on knowledge of pelvic floor muscle exercise and postoperative discomfort and complications after cesarean section, so as to improve the effect of pelvic floor muscle exercise. Methods A total of 108 patients who underwent cesarean section from August 2015 to August 2016 were randomly divided into experimental group and control group by the random number table method, with 54 cases in each group. The puerperae in the control group were treated with conventional pelvic floor muscle exercise. In the experimental group, the nursing staff and the patients' one-on-one steering group was set up and the individualized pelvic floor muscle exercise was carried out during the hospitalization. The puerperae of the two groups were compared in stress urinary incontinence, pelvic organ prolapse, defecating unfinished feeling, pelvic bulge, lower genital tract discomfort, the level of cognition and behavior of pelvic floor muscle exercise and the puerpera satisfaction in the reexamination after 6 weeks of discharge. Results The number of puerperae with stress urinary incontinence and pelvic organ prolapse in the experimental group was less than that in the control group, and the difference was statistically significant (P< 0.05). The number of puerperae with defecating unfinished feeling, pelvic bulge and lower genital tract discomfort in the experimental group was significantly less than that in the control group (P< 0.05). The score of knowledge level of the pelvic floor muscle in the experimental group was (4.60±1.38), and the exercise behavior score was (4.36±1.17). The score of knowledge level of the pelvic floor muscle in the control group was (2.26±1.27), and the exercise behavior score was (2.57±1.24). The differences were statistically significant (P<0.05). The satisfaction rate was 81.48% in the experimental group and 42.59% in the control group (χ2=5.793,P<0.05). Conclusions The establishment of the steering group for maternal recovery exercise guidance can improve the maternal knowledge of exercise, so as to reduce all kinds of discomfort and complications, improve pelvic floor muscle exercise effect and improve maternal satisfaction.

Objective To explore the effects of piperine on cell proliferation and migration in angiotensin Ⅱ (Ang Ⅱ)-treated rat airway smooth muscle cells (ASMCs).Methods The primary ASMCs of rats were cultured by improved tissue-piece digestion inoculation and trypsin digestion.MTT assay was used to detect the effects of Ang Ⅱ and Ang Ⅱ receptor antagonist losartan on cell proliferation activity.After treatment with Ang Ⅱ and piperine, the cell proliferation activity, the cell cycle distribution and the cell migration were detected by MTT, flow cytometry and Transwell assay respectively.ERK1/2 inhibitor PD98059 and losartan were then applied to determine the expression of cyclin D1, MMP-9, p-ERK1/2, ERK1/2, and β-actin proteins by Western blot assay.Results After 24 h culture, Ang Ⅱ treatment promoted the cell proliferative activity in rat ASMCs (P<0.05), and the promotive effect of 10-7 mol/L Ang Ⅱ was the most significant.Additionally, losartan blocked the Ang Ⅱ-induced cell proliferative activity in rat ASMCs (P<0.05).10-7 mol/L Ang Ⅱ treatment resulted in the elevated cell proliferative activity, higher S phase fraction, increased migrated cell number, and enhanced expression of cyclin D1, MMP-9and p-ERK1/2 proteins (P<0.05);these effects were dose-dependently reversed by piperine.Both PD98059 and losartan blocked Ang Ⅱ-induced expression of p-ERK1/2, cyclin D1 and MMP-9 proteins in rat ASMCs.Conclusions Piperine may inhibit Ang Ⅱ-induced cell proliferation and cell migration via ERK1/2 signaling pathway in rat ASMCs.