Objective To investigate the calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)signaling pathway and expression of brain-derived neurotrophic factor(BDNF)isoforms in mouse model of cognitive dysfunction secondary to repetitive mild traumatic brain injury(rmTBI).Methods A total of 63 male C57BL/6J mice(5 weeksd old,werghing 16～17 g)were divided into model group(n=50)and control group(n=13).The mice of the model group received modified weight drop and repeated head impacts to establish a model of rmTBI,and the mice from the control group were only given anesthetic treatment.From the 30th day after the end of modeling,Morris water maze test was applied to evaluate the spatial learning and memory abilities,and the relative data was evaluate for correlation analysis.According to the taxonomy of cognitive levels,the model group was further stratified into high-,medium-and low-performance groups.After the mice with medium-performance group were eliminated,and the indicators of water maze test were compared among the high-performance,low-performance,and control groups.After the behavioral experiment,Western blotting was conducted to detect the expression of CaMKII,α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor(AMPAR)subunits(GluR1,p-GluR1,GluR2),and different isoforms of BDNF(mBDNF,proBDNF)in the prefrontal cortex and hippocampus.The expression levels were compared among the groups.Results ① There were significant correlations among the water maze-related indicators(P<0.05).The mice in the model group were divided into 3 groups of high-(n=31),medium-(n=11)and low-performance(n=8)levels through hierarchical clustering,and there were differences in cognitive levels in the high-performance,low-performance and control groups.② The phosphorylation level of GluR1 in the hippocampus was significantly decreased in the high-performance group than the control group and the low-performance group(P<0.05).When compared with the control group,the expression of GluR1 and GluR2 in the prefrontal cortex of the low-performance group was increased(P<0.05),and the expression of GluR2 and CaMKⅡ in the prefrontal cortex of the high-performance group was increased(P<0.05).The low-performance group obtained obviously lower GluR1/GluR2 ratio than the high-performance group(P<0.05).③ When compared with the control group,the low-performance group exhibited notably elevated expression of proBDNF and mBDNF(P<0.05)and mBDNF/proBDNF(P<0.05)in the prefrontal cortex and hippocampus,while the high-performance group had enhanced expression of mBDNF in the prefrontal cortex(P<0.05).Conclusion In the chronic phase of rmTBI,prognosis of good cognitive function is accompanied by up-regulation of CaMKⅡ signaling pathway,and the difference in cognitive function is accompanied by the change in proportions of different AMPAR subunits on the postsynaptic membrane.In the cognitive impairment group,there is an overexpression of 2 types of BDNF isoforms and an increase in the conversion rate of mBDNF.

Objective To investigate the effect and clinical efficacy of dapagliflozin on homocysteine(Hcy),uric acid(UA),and cystatin C(Cys C)in elderly patients with type 2 diabetes mellitus(T2DM)complicated by nephropathy and hypertension.Methods A total of 292 patients diag-nosed with T2DM nephropathy and hypertension admitted to our hospital between December 2022 and June 2023 were retrospectively recruited,and based on their medication regimens,they were divided into dapagliflozin group(147 cases)and control group(145 cases).After all of them were followed up for 3 months,the serum levels of Hcy,UA,cys C,urinary microalbumin/urinary creatinine ratio(UACR),estimated glomerular filtration rate(eGFR),and other metabolism-related indicators were measured and compared before and after treatment.Pearson correlation analysis was used to determine the correlation between Hcy and UA,while logistic regression analysis was employed to identify risk factors for proteinuria among the patients with T2DM ne-phropathy and hypertension.Results After treatment,the BMI,SBP,DBP,FBG,glycosylated Hb,TC,TG,LDL-C,UA,Cys C,Hcy,insulin resistance index(HOMA-IR),and UACR were all decreased in comparison to their levels before treatment(P＜0.05).Dapagliflozin treatment resul-ted in more significant declines in BM1,FBG,LDL-C,UA,Cys C,Hcy,HOMA-IR,and UACR when compared with the control group(P＜0.05,P＜0.01).Pearson correlation analysis revealed that the relationship between Hcy and UA was positively correlated across the entire population(r=0.560,P＜0.01),as well as among males(r=0.510,P＜0.01)and females(r=0.640,P＜0.01).Multivariate logistic regression analysis identified female gender,diabetic peripheral neu-ropathy,TC,eGFR,and Hcy ≥15 μmol/L as independent risk factors for proteinuria among eld-erly patients with T2DM nephropathy and hypertension(P＜0.05,P＜0.01).Conclusion Dapa-gliflozin,a novel antidiabetic agent,may offer further renal protection by lowering Hcy and UA levels in patients with T2DM nephropathy and hypertension.It can potentially decelerate the pro-gression of proteinuria and improve patient's outcomes.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

Objective     To analyze the clinical efficacy and safety of endostar or carboplatin combined with endostar intracavitary perfusion in the treatment of malignant serous cavity effusion. Methods     We retrospectively reviewed the clinical data of 78 cancer patients with malignant serous cavity effusion who received paracentesis and intracavitary endostar, or carboplatin combined with endostar in Shengjing Hospital of China Medical University between November 2011 and November 2016. There were 42 males and 36 females at a median age of 62 years ranging from 17 to 78 years. According to treatment methods, 78 patients were divided into two groups, in which 33 patients received intracavitary endostar combined with carboplatin (a combination group, 15 males and 18 females at a median age of 56 years ranging from 17 to 66 years), and 45 patients received intracavitary endostar (an endostar group, 27 males and 18 females at a median age of 63 years ranging from 38 to 78 years). The efficacy and safety of two methods were analyzed and compared. Results     The response rate in the combination group was 75.8%, which was higher than that in the endostar group (60.0%, P=0.035). In quality of life improvement, there was no statistical difference between the two groups (P=0.113). The incidence of fatigue, myelosuppression and gastrointestinal reactions in the endostar group was significantly lower than that of the combination group (P=0.006, 0.000 and 0.017, respectively). Analysis of long-term efficacy revealed that the median time to progress (TTP) in the combination group and endostar group was 171 days and 143 days, respectively (P=0.030). Conclusion     Intracavitary infusion of endostar alone, or carboplatin combined with  endostar is effective and tolerable for controlling malignant serous cavity effusion. But for the patients with poor physical state who can not tolerant platinum perfusion, intracavitary infusion of endostar alone can be adopted to control malignant serous cavity effusion.

Objective The aim of this study was to retrospectively review the efficacy and safety of treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC).Methods A total of 98 patients treated in our hospital between January 2010 and December 2015 were enrolled in this study.Patients were divided into three groups:the thoracic radiotherapy (TRT) alone,concurrent chemoradiotherapy,and sequential chemoradiotherapy groups.The progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method,and compared with the log-rank/Breslow test.The prognostic factors were analyzed using the Kaplan-Meier and Cox multivariate proportional hazards models.Results The median PFS in the concurrent therapy group was longer than that in the TRT alone group (P ＜ 0.05).The median OS was improved in patients treated with concurrent or sequential therapy than in the TRT alone group (P ＜ 0.05).N stage,chemotherapy regimens,and radiotherapy modalities were independent prognostic factors of PFS in all patients (P ＜0.05).Similarly,N stage was an independent prognostic factor of OS in all patients (P ＜ 0.05).Overall,the treatment was deemed safe.The occurrence of hematotoxicity related to Karnofsky performance score (KPS) and chemotherapy regimens (P ＜ 0.05).Conclusion Patients with a lower N stage who received cisplatin-based double chemoradiotherapy demonstrated improved survival rates.Survival was significantly improved in LA-NSCLC patients treated with concurrent or sequential therapies compared with TRT alone.Overall,the treatment is safe.KPS and chemotherapy combination regimens may increase the occurrence of hematotoxicity.

Objective To investigate the situation of sexual partners and related factors among men who have sex with men (MSM) in college students.Methods Snowball sampling and Convenience sampling were both used to recruit MSM from colleges in Tsingtao in 2016.Questionnaire-based interviews were conducted to collect data of socio-demographic and situation of sexual partners.Sample Size was estimated based on cross-sectional study,and theoretical 267.SPSS 17.0 software was used for statistical analysis.Results A total of 300 MSM,average aged 20.7,were analyzed.Both first sex partner and the last same-sex sexual partner were mct instantly,with proportions as 58.7％ (176/300) and 62.3％ (187/300) respectively.Among all the MSM,88.3％ (265/300) preferred selecting men as sex partners and 42.7％ (128/300) enjoyed finding sex partners in college,while 86.0％ (258/300) preferred finding their sex partners through intemet.Conclusions Intemet had been the major way of looking for sex partner among MSM in college students,the male sexual partner were met instantly.We should focus on men who have sex with men and their sexual health among college students to prevent and control HIV/AIDS.

Objective:This study was performed using preclinical transplanted animal experiments to analyce the effects and mechanisms of third-generation EGFR-TKIs combined with anti-angiogenic therapy, thereby providing theoretical basis for further clinical trials. Methods:Researchers constructed the transplant BALB/C nude mice models with H1975 lung adenocarcinoma cell line (EGFR T790M) and divided the mice into four groups and treated them with osimertinib (2.5 or 5 mg/kg/day, gavage) alone or plus bevacizumab (5 mg/kg/twice weekly, i.p.) when the tumors reached approximately 0.4-0.6 cm3 in volume. The tumor growth curve of tumor volume was drawn according to the time in every group. After 2 weeks of treatment, the mice were killed and the tumors were processed for immunohistochemical staining and Western blot analysis. Immunostaining was performed to detect:HIF-1α, VEGF, and microvessel density (MVD) by using SP method on paraffin sections. Western blot analysis was used to analyze the protein expression levels of EGFR, AKT, and ERK signal transduction pathways. Results:After 2 weeks of treatment in high-and low-dose osimertinib alone, tumor volume in the high-dose group was significantly less than in low-dose osimertinib-alone group (P<0.05). VEGF, HIF-1αexpression, and MVD were significantly low in the high-dose osimertinib-alone group (P<0.05). Increasing doses of osimertinib induced dose-dependent weakening of the p-EGFR, p-AKT, and p-ERK expression levels (P<0.05). In the low-dose osimertinib-plus-bevacizumab group and low-dose osimertinib-alone group, no significant difference in tumor volume and the above factors was observed. In the low-dose osimertinib-plus-bevacizumab group and high-dose osimertinib-alone group, tumor volumes did not exhibit significant difference (P=0.178). Moreover, VEGF, HIF-1αexpression, and MVD exhibited no significant difference. No significant difference in the p-EGFR, p-AKT, and p-ERK expression levels was found between high-dose osimertinib-alone group and low-dose osimertinib-plus-bevacizumab group (P>0.05). In the high-dose osimertinib-plus-bevacizumab group, tumor growth was not significantly greater than that in the high-dose osimertinib-alone group (P=0.642). No significant difference was observed in the above factors.In the high-and low-dose osimertinib-plus-bevacizumab groups, tumor volume and the above factors did not exhibit significant differences (P>0.05). Conclusion:Osimertinib has obvious antitumor effects in EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab has a synergetic inhibitory effect with osimertinib against EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab enhanced the antitumor effects of osimertinib by reducing VEGF expression and the microvascular density of the tumor, thereby improving the tumor microenvironment. Bevacizumab can enhance the effect of osimertinib by suppressing EGFR, ERK, and AKT phosphorylation, thereby synergistically inhibiting EGFR activation and downstream signaling.

OBJECTIVE: To systematically evaluate the application of microcapsuled cell or encystation materials for treating diabetes mellitus at hone or abroad in recent years.METHODS: A computer-based online search of PubMed database was undertaken to identify related articles about the microcapsulated cell or encystation material for treating diabetes mellitus published from 1980 to 2009 by using the key words of "microcapsulation, islet, transplantation" in English. Meanwhile, we search CNKI for relevant articles published between 1999 and 2009 with the same key words in Chinese. The related randomized, controlled, and clinical studies were collected according to conclusion and exclusion criteria.RESULTS: Among 25 articles, there were 46 patients with type I diabetes mellitus, 106 rats, 20 pigs, and 25 monkeys. The experimental results showed that both the microcapsulated islets and non-microcapsulated islets could secrete insulin and decrease blood glucose level. The normal blood glucose level with microcapulated islets could be maintained for a long time.Thus, microcapsule had a great immune isolation reaction.CONCLUSION: After transplantation, microencapsulated islet cells could improve and adjust abnormal glycometabolism of patients with diabetes mellitus; furthermore, the immunoisolation effect of microcapsule could eliminate or relieve the immunological rejection of receptors to allograft or xenograft, while it could also relieve or eliminate dependence on immunosuppressive drugs. Appropriate material of microcapsule, reasonable process, advanced equipment, advanced separation and purification technologies of islet, and suitable site for transplantation could improve the function of artificial islet cell, enhance the anti-machinery and chemical strength of microencapsuiated islet, improve biocompatibility, and prolong survival time.

Objective To study the relationship between serum C-reactive protein(CRP)levels and insulin resistance(IR)in patients with hyperglycemia and obesity.Methods Fasting plasma glucose(FPG),2h plasma glucose(2hPG),fasting insulin(INS),patient height and weight were measured.Body mass index(BMI)and Homa insulin resistance index(Homa-IR)were calculated.Based on BMI and PG,the participants were divided into 4 groups:normal control group(30 cases),simple obesity group(30 cases),impaired glucose regulation(IGR)obesity group(30 cases)and type 2 diabetic obese group(30 cases).Serum C-reactive protein levels were measured with immunoturbimetric assay.Results(1)CRP and the Homa-IR in other groups were significantly increased comparing with normal control group,with statistical difference observed(P