Background Our previous study showed that the expression level of glial fibrillary acid protein (GFAP) increases in astrocytes and Müller cells of retina in chronic hypertensive eye,and this change was clarified to be associated with the damage process of the retinal ganglion cells (RGCs).Aquaporin 4 (AQP4) exists in neural glial cells,so we conjecture AQP4 plays a role in the regulating GFAP expression in glaucomatous eye.Objectives This study was to investigate whether AQP4 gene can regulate the expression of GFAP in retina and explore the effect of AQP4 on RGCs damage of glaucoma.Methods Chronic ocular hypertensive eye models were established by cauterizing the scleral venous in the left eyes of 30 male AQP4-/-mice and 30 male wild type (WT) mice with the same background,and the right eyes served as control eyes.The intraocular pressure (IOP) was measured with Icare rebound tonometer at 1 day,3,7,14 and 28 days respectively and the retinas were isolated from 6 of each types of mice at the corresponding time points.The expression of GFAP in the retina was detected by Western blot.The use and care of the experimental animals followed ARVO Statement.Results The IOP was significantly higher in the model eyes than that of the control eyes 1 day,3,7,14 and 28 days in both AQP-/-mice (t =15.29,16.02,13.77,14.34,12.40,all at P＜0.05) and WT mice (t =17.65,14.91,15.97,13.41,12.53,all at P ＜0.05).GFAP was expressed in the control eyes both of the AQP4-/-mice and the WT mice.The expressing level of GFAP (GFAP/β-actin) in retinas was 1.00±0.00,1.99±0.29,4.05±0.69,4.47±0.48,3.21±0.35 and 3.25±0.53 in the control eyes and 1-,3-,7-,14-,28-day model eyes of WT mice; and those in the AQP4-/-mice were 1.00±0.00,1.69±0.31,2.27 ±0.55,2.79 ± 0.39,1.93 ± 0.31 and 1.54 ± 0.40,with a significant difference in the expressing level of GFAP in various time points (F =9.54,P＜0.05).In addition,significant gradually elevation of GFAP expression were seen in the WT mice and gradually decline of GFAP expression was found in the AQP4-/-mice with the lapse of time (all at P＜0.05).No significant difference was seen in the expression of GFAP in the control eyes between the WT mice and AQP4-/-mice (P＞0.05).However,the expression level of GFAP in retina was significantly higher in the WT mice than that of A QP4-/-mice 3,7,14 and 28 days after operation (t =4.51,7.95,6.12,5.76,all at P＜0.01).tonelusions In chronic high IOP mice,AQP4 gene plays an important role in retinal damage by upregulating the expression of GFAP in retina and promoting the activation of RGCs.AQP4 probably is a new target of treatment of glaucoma.

Objective To build learning evaluation system and indicators connotation of problem-based in small-group teaching model.Methods Delphi technique was used to build learning evaluation system of problem-based for course of nursing education through a two-round expert consultation among 30 experts in Zhejiang province.Results The experts' authority coefficient was 0.89,determination coefficient was 0.90,and familiar confficient was 0.88.The finally learning evaluation system of problem-based for course of nursing education consisted of 3 first-level indicators,14t second-level indicators and 41 third-level indicators.The coordination coefficients of first-level indicators and second-level indicators were 0.37 and 0.31,respectively,there was significant difference,P＜0.01.Conclusion This project has a rigorous and reliable construction process with strong theoretical and practical significance,and could be used as a guidance and reference for problem-based in small-group teaching for course of nursing education.

Ten ATP binding cassette (ABC) transporters are confirmed to be associated with resistance against anticancer drugs. To investigate the relationship between these ten ABC transporters and the nasopharyngeal carcinoma cell line CNE2 resistant to cisplatin, cisplatin and cisplatin with 5-fluorouracil were used to induce the CNE2 cell to acquire the drug-resistance for 1 year. After these cells were cultured without drugs for 2 months, the MTT assay method was used to determine the dose-effect relationship of cisplatin and resistant index. Quantitative real time polymerase chain reaction was used to detect the mRNA expression of ten ABC transporters in CNE2 and the drug-resistant CNE2 cells, and the result was confirmed by immunocytochemical method. The results of MTT method showed that two cell lines resistant to cisplatin (named as CNE2/DDP) and cisplatin with 5-fluorouracil (named as CNE2/DDP+5Fu) were established, with resistant index 2.58 and 5.31, respectively. Of ten ABC transporters, only ABCC2 was found to be up-regulated both in CNE2/DDP and CNE2/DDP+5Fu cells, for increasing about 2.50 and 4.08 folds, respectively. The results of immunocytochemical method also confirmedthat the expression of ABCC2 in CNE2/DDP and CNE2/DDP+5Fu cells were stronger that that in CNE2 cell. Furthermore, ABCC2 protein was found to be located at nuclear membrane of CNE2/DDP +5Fu cell but not at nuclear membrane of CNE2 cell. The results suggest that ABCC2 may play an important role in cisplatinresistance of nasopharyngeal carcinoma cell line CNE2.

Objective: Toexplore work process-oriented theory nursing ward round, research work process-oriented theory nursing ward round on critical thinking capacity of nursing undergraduates. Methods: Totally 80 Elective nursing ward round courses of nursing undergraduates were divided into the experimental A group and the experimental b group with 40 cases in each group. The experimental A group select the beginning of 9 weeks on Until, the experimental B group select the after of 9 weeks on Until. The nursing undergraduates were assessed by CTDI-CV on first, ninth, eighteenth weeks to evaluate the effect of the two groups. Results: Main effect of group factor and time factor of CTDI-CV had statistical significance (P<0.05) . There were significant interaction in the scores of CTDI-CV. Simple effect analysis demonstrated the scores of CTDI-CV in the experimental A group were higher than those of the experimental b group after the intervention (P<0.05) . Two groups of on first, ninth, eighteenth weeks measured values compared the effect of amount of F_B<F_A, the experimental group A intervention effect was better than in the experimental group B intervention. Conclusions For nursing undergraduates guided based on the working process of the curriculum of nursing ward round the critical thinking ability had good practice guidance, and on the start time to choose university grade three semester two on 9 weeks before commencement of nursing undergraduates promotes higher critical thinking ability.

Objective:To compare the clinical value of ultrasonography, multi-slice spiral computed tomography(MSCT) and magnetic resonance cholangiopancreatography(MRCP) in the early diagnosis of cholelithiasis.Methods:The clinical data of 140 patients with suspected cholelithiasis treated in Yuyao People's Hospital from January 2017 to March 2019 were reviewed.All the patients were examined by ultrasonography, MSCT and MRCP.Based on the results of operation, the diagnostic results of ultrasonography, MSCT and MRCP were compared, and the consistency between the diagnostic results was analyzed.Results:Of 140 patients with suspected cholelithiasis, 100 cases were confirmed to be cholelithiasis by operation.The sensitivity, specificity and accuracy of MRCP were 97.00%(97/100), 95.00%(38/40) and 96.43%(135/140), which were higher than those of ultrasonography[87.00% (87/100), 80.00%(32/40), 85.00%(119/140)] and MSCT[89.00%(89/100), 77.50%(31/40) and 85.71%(120/140)](χ 2=6.794, 4.114, 10.854, χ 2=4.916, 5.165, 9.882, all P<0.05). The consistency between MRCP and surgical diagnosis was good, but the consistency between ultrasound, MSCT and surgical diagnosis was moderate. Conclusion:The accuracy of MRCP is better than ultrasound and MSCT in the diagnosis of cholelithiasis, which has good diagnostic value and can reduce the missed diagnosis and misdiagnosis of cholelithiasis.

OBJECTIVETo investigate the impact of long-time and short-time blood pressure variability (BPV) on glomerular filtration rate (eGFR) in elderly population.

METHODSA total of 2 464 participants aged of ≥60 years old without history of stroke and coronary heart disease were selected with random sampling method from the individuals underwent health check up in Tangshan Kailuan Hospital, Kailuan Linxi Hospital, Kailuan Zhaogezhuang Hospital between 2006 and 2013. The study participants were asked to join a face-to-face interview every two years. Long-time BPV was defined as the standard deviation of all SBP values at the baseline visit and following visits, short-time BPV was defined as the standard deviation of day time blood pressure and night time blood pressure which was derived from 24 hours ambulatory blood pressure monitoring. Multivariate linear regression models were used to test the impact of long- and short-time BPV on eGFR.

RESULTSThe study included 3 participants groups including the long-time SBPV group (2 279 participants), the short-time SBPV group (1 636 participants) and the long- plus short-time SBPV group (1 632 participants). Participants were further sub grouped by median value (NO.1median value). eGFR in the long-time SBPV NO.1 and NO.2 group was 83.19 and 81.49 ml·min(-1)·1.73 m(-2) respectively, in the short time SBPV NO.1 and NO.2 group was 83.53 and 80.81ml·min(-1)·1.73 m(-2) of the day time, and was 83.20 and 81.14 ml·min(-1)·1.73 m(-2) of the night time, respectively. eGFR in the long- plus short-time SBPV NO.1 and NO.2 group was 83.21 and 81.08 ml·min(-1)·1.73 m(-2) of the long-time SBPV, and was 83.53 and 80.75 ml·min(-1)·1.73 m(-2) of the day time, and was 83.18 and 81.11 ml·min(-1)·1.73 m(-2) of the night time. Significant linear relationship was found between higher day time SBPV and lower eGFR (P<0.05). After adjusting for confounding parameters including age, sex, body mass index, 1 mmHg(1 mmHg=0.133 kPa) of day time SBPV increase was related 0.21 ml·min(-1)·1.73 m(-2) eGFR decrease (P<0.05).

CONCLUSIONThe higher day time SBPV is associated with reduced eGFR in the elderly population.Clinical Trail Registry Chinese Clinical Trial Registry, ChiCTR-TNC-11001489.

Results of the IMbrave150 clinical study showed that atezolizumab plus bevaci-zumab have better overall survival and progression-free survival than sorafenib in the treatment of hepatocellular carcinoma patients. However, hepatocellular carcinoma patients with esophageal varices were not included in the IMbrave150 clinical study mainly considering the bleeding risk of patients undergoing treatment of bevacizumab. The authors introduce the atezolizumab plus bevaci-zumab treatment of an advanced hepatocellular carcinoma patient with moderate esophageal varices. By reducing the dose of bevacizumab, the patient achieved an excellent curative effect.

Objective:To investigate the clinical efficacy and mechanism of Ganoderma lucidum hypoglycemic formula in the treatment of insulin resistance in patients with type 2 diabetes mellitus (T2DM) with liver and kidney yin deficiency. Methods:A total of 86 patients with T2DM with liver and kidney yin deficiency who were diagnosed and treated at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine from January 2021 to February 2022 were included in this study. These patients were divided into a control group and a treatment group, with 43 patients in each group using a 1:1 ratio using the sealed envelope method. Both groups were treated with standardized Western medicine. The treatment group was also treated with the Ganoderma lucidum hypoglycemic formula. All patients were followed up for 12 weeks. The clinical symptoms, curative effect, glucose and lipid metabolism, inflammatory factors, oxidative stress change, and safety were compared between the two groups. Results:The total response rate in the treatment group was 88.4% (38/43), which was significantly higher than 53.5% (23/43) in the control group ( χ2 = 12.69, P < 0.001). After treatment, the traditional Chinese medicine syndrome score, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, insulin resistance index, total cholesterol, triglyceride, tumor necrosis factor α, and interleukin-6 decreased in each group. The amplitudes of decrease of the above indexes were greater in the treatment group compared with the control group (all P < 0.05). C-peptide in the fasting state, C-peptide at 2 hours after a diet, and superoxide dismutase increased in each group. The amplitudes of increase of the three indexes were greater in the treatment group compared with the control group (all P < 0.05). Conclusion:Ganoderma lucidum hypoglycemic formula can greatly improve insulin resistance and glucose and lipid metabolism in T2DM patients with liver and kidney yin deficiency. The underlying mechanism may be to further reduce the inflammatory response and anti-oxidative stress by down-regulating tumor necrosis factor α and interleukin-6 levels and up-regulating superoxide dismutase level, thereby effectively alleviating insulin resistance in T2DM.

Objective:To explore the different design of readiness assurance process (RAP) and application in TBL teaching of rehabilitation medicine, and to compare the teaching effects.Methods:A total of 40 students who had clinical rotation in our department were chose as research subjects, and they were taught with TBL teaching. Two chapters of "Stroke Rehabilitation" and "Spinal Cord Injury Rehabilitation" were chosen for the two lectures. During the course of "Stroke Rehabilitation", the RAP adopted open-ended questions, and the application part simulated Teamwork meetings. In the course of "Spinal Cord Injury Rehabilitation", the RAP used close-ended multiple-choice questions, and the application part simulated making rehabilitation plan. At the end of the two lectures, questionnaires were send to students.Results:For the RAP part, more students preferred open-ended questions. In the application part, students preferred to make rehabilitation plan.Conclusion:The process of clinical diagnosis and treatment and the formulation of rehabilitation plan in clinical practice of rehabilitation medicine has been applied to different parts of TBL teachings, and students are favor of this teaching method, which provides a reference for the future TBL teaching design of rehabilitation medicine.

Objective:To investigate the differentially expressed microRNAs (miRNAs) in human gastric carcinoma SGC-7901 cell-derived exosomes induced by Helicobacter pylori ( H. pylori), providing new clues for further elucidating the carcinogenic mechanism of H. pylori. Methods:Ultracentrifugation and exosome extraction kit were used to extract the exosomes released by the H. pylori-stimulated and negative control group, and transmission electron microscope(TEM), nanoparticle tracking analysis(NTA) and Western blot experiments were employed to identify exosomes. Then, exosomes were labeled with the fluorescent dye PKH67 and co-cultured with THP-1-derived macrophages. The internalization of exosomes by macrophages was observed by laser confocal fluorescent microscopy. Additionally, miRNA microarray chips were performed to detect the differentially expressed miRNAs of exosomes from the two groups of cells. Real-time fluorescence quantitative PCR (qRT-PCR) was used to verify the expression of four differentially expressed miRNAs. Furthermore, the target genes and their functions as well as the possible signal pathways involved of partial differentially expressed miRNAs were predicted and analyzed by bioinformatics software. Differentially expressed miR-382-5p was labeled by Cy3 to observe whether it could be transferred to macrophages through exosomes. The expression of phenotype molecule CD206 and the cytokines TNF-α, IL-6 and IL-10 in miR-382-5p mimic-transfected macrophages were analyzed by qRT-PCR and ELISA, and the proportion of cells expressing CD206 and HLA-DR was analyzed by flow cytometry. Results:The extracted exosomes were consistent with exosome morphology and highly expressed the surface marker proteins CD9, CD63 and TSG101. After co-culturing with THP-1 derived macrophages for 12 h, the exosomes could be internalized by macrophages. Compared with the control group, there were 130 up-regulated miRNAs and 111 down-regulated miRNAs in the H. pylori-stimulated group. Bioinformatic analysis showed that the potential target genes of partial differentially expressed miRNAs were mainly involved in the regulation of PI3K-AKT, NF-κB, JAK-STAT, stem cell pluripotency and other inflammation and tumor-related pathways. miR-382-5p could be transferred to macrophages through exosomes, and induced the expression of M2-type phenotype molecule CD206 and cytokines IL-10 in macrophages, while inhibited the expression of TNF-α and IL-6 and increased the proportion of CD206 high HLA-DR low cells. Conclusions:H. pylori treatment caused a significant change in the expression level of exosome miRNAs in SGC-7901 cells. Bioinformatics analysis demonstrated that the prospective targets of these differentially expressed miRNAs might play an important role in the regulation of inflammation and tumor-related signaling pathways. miR-382-5p might induce the M2-type polarization of macrophages.