Objective To explore the neuro-protective effect of remimazolam(Rem)on traumatic brain injury(TBI)in rat models.Methods A TBI rat model was constructed.The rats were randomly divided into control group,traumatic brain injury group(TBI group),low-dose and high-dose remimazolam groups(Rem-L,Rem-H groups),and high-dose remimazolam+Jagged1 group(Rem-H+Jagged1 group),with 12 rats in each.All rats were evaluated for neurological deficits.The serum level of inflammatory factors like tumor necrosis factor α(TNF-α)and interleukin-1β(IL-1β)were detected by ELISA.HE staining microscopy was used to observe the changes of brain histopathology.The expression of glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptation molecule 1(IBA1)were detected by immunohistochemistry.Western blot was applied to detect the ex-pression of Notch,Notch 1 intracellular domain(NICD)and Hes-1 protein in the brain tissue.Results Compared with the control group,the TBI group showed a larger area of brain tissue defect and edema,with more activated glial cells and fragmented,concentrated and deeply stained neuronal nuclei,indistinct nucleoli,deeply stained cy-toplasm,and partial neuronal necrosis The neurological deficit score was higher,level of TNF-α and IL-1β and the expression of GFAP,IBA1,Notch,NICD,and Hes-1 all elevated(P＜0.05).Remazolam reduced brain tissue defect area,alleviated edema,inhibited glial cell activation and neuronal apoptosis,and reduced nerve function deficit score,the level of TNF-α and IL-1β,and the expression of GFAP,IBA1,Notch,NICD and Hes-1(P＜0.05).Jagged1 could aggravate brain tissue injury,increase neural function deficit score,levels of TNF-α and IL-1β and expressions of GFAP,IBA1,Notch,NICD and Hes-1(P＜0.05).Conclusions Remimazolam may have neuroprotective effects as shown by TBI rat models,and the underlying mechanism is potentially related to the inhibition of the Notch/Hes-1 signaling pathway.

Objective:To comprehensively evaluate treatment outcomes and assisted reproductive approaches in infertility patients with CYP17A1-deficient congenital adrenal hyperplasia [including 17α-hydroxylase/17,20-lyase deficiency (17-OHD) and isolated 17,20-lyase deficiency (IDL)]. Methods:In this study, PubMed, Embase, Web of Science, Ovid, CNKI, Wanfang Data base, and the Chinese Biomedical Literature Database were systematically searched. The data extracted included basic patient information, treatment plans, and pregnancy outcomes, which were then analyzed descriptively.Results:Totally 19 articles were included, covering 23 cases of successful live births. Among the 23 patients with successful live births, there were 19 patients with 17-OHD, including 17 cases became pregnant through in vitro fertilization and embryo transfer (IVF-ET), 1 case through natural pregnancy, and 1 case through oocyte donation pregnancy; there were 4 cases with IDL, including 2 cases through natural pregnancy and 2 cases through IVF-ET pregnancy. Conclusion:IVF-ET is the preferred fertility treatment option for patients with partial form of 17-OHD. For IDL patients who have natural ovulation, natural pregnancy can be attempted. Glucocorticoids play a crucial role in improving pregnancy outcomes, but their use needs to be individualized.

Objective:To comprehensively evaluate treatment outcomes and assisted reproductive approaches in infertility patients with CYP17A1-deficient congenital adrenal hyperplasia [including 17α-hydroxylase/17,20-lyase deficiency (17-OHD) and isolated 17,20-lyase deficiency (IDL)]. Methods:In this study, PubMed, Embase, Web of Science, Ovid, CNKI, Wanfang Data base, and the Chinese Biomedical Literature Database were systematically searched. The data extracted included basic patient information, treatment plans, and pregnancy outcomes, which were then analyzed descriptively.Results:Totally 19 articles were included, covering 23 cases of successful live births. Among the 23 patients with successful live births, there were 19 patients with 17-OHD, including 17 cases became pregnant through in vitro fertilization and embryo transfer (IVF-ET), 1 case through natural pregnancy, and 1 case through oocyte donation pregnancy; there were 4 cases with IDL, including 2 cases through natural pregnancy and 2 cases through IVF-ET pregnancy. Conclusion:IVF-ET is the preferred fertility treatment option for patients with partial form of 17-OHD. For IDL patients who have natural ovulation, natural pregnancy can be attempted. Glucocorticoids play a crucial role in improving pregnancy outcomes, but their use needs to be individualized.

Objective:To construct the evaluation index system of "early clinical contact" education of undergraduate medical students, and to provide guidance for the evaluation of "early clinical contact" education in medical teaching.Methods:The evaluation index system of "early clinical contact" education of undergraduate medical students was constructed by literature research, Delphi expert consultation and analytic hierarchy process, and the weight of each index was determined. Excel 2010 and SPSS 25.0 were used to make data entry and statistical analysis.Results:The enthusiasm of experts in the two rounds of expert consultation were 100.00%(26/26) and 96.15%(25/26) respectively, the expert authority coefficients were 0.900 and 0.920, and the coordination coefficients were 0.255 and 0.175 respectively ( P < 0.05). The evaluation index system included 4 first-class indexes, 12 second-class indexes and 47 third-class indexes. Conclusion:The index system has high scientificity and reliability. After further verification, it can be used as an evaluation tool for the teaching quality of "early clinical contact" education of undergraduate medical students.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Objective:To investigate the prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in patients with elderly classical Hodgkin′s lymphoma (cHL). Methods:From April 2011 to April 2020, the pretreatment clinical and 18F-FDG PET/CT metabolic parameters of 42 elderly cHL patients (29 males and 13 females, median age 69 years) pathologically confirmed in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained with 41%SUV max as the threshold. ROC curve analysis was applied to obtain the best prognostic cut-off value of SUV max, MTV and TLG. Kaplan-Meier method and log-rank test were used for univariate survival analysis, and Cox proportional hazard regression model was used for multivariate survival analysis. Results:SUV max, MTV and TLG of 42 elderly cHL patients were 16.49(12.24, 23.59), 79.29(26.29, 184.51) ml and 729.02(206.03, 2 073.98) g, respectively. ROC curve showed that the AUCs of SUV max, MTV and TLG were 0.425, 0.882 and 0.832, respectively, and the best prognostic cut-off values were 16.49, 82.38 ml and 556.26 g, respectively. Univariate analysis showed that age, B symptoms, lactate dehydrogenase (LDH) level, Hb content, Ann Arbor stage, German Hodgkin Study Group (GHSG) score, MTV and TLG were relative factors affecting progression-free survival (PFS) rate ( χ2 values: 4.50-12.60, all P<0.05), and age, B symptoms, LDH level, Ann Arbor stage, GHSG score, MTV and TLG were relative factors affecting overall survival (OS) rate ( χ2 values: 5.20-11.17, all P<0.05). Multivariate analysis showed that MTV (relative risk ( RR)=5.370, 95% CI: 1.697-16.277) and TLG ( RR=4.854, 95% CI: 1.228-23.352) were independent prognostic predictors of PFS rate (both P<0.05), and GHSG score ( RR=3.761, 95% CI: 1.092-12.955; RR=3.668, 95% CI: 1.068-12.571), MTV ( RR=6.173, 95% CI: 1.431-16.322) and TLG ( RR=5.162, 95% CI: 1.200-22.199) were independent prognostic predictors of OS rate (all P<0.05). Conclusion:MTV and TLG in pretreatment 18F-FDG PET/CT are independent prognostic factors for predicting PFS and OS in patients with elderly cHL patients, which have certainly reference value for prognosis.

The interleukin family can directly or indirectly stimulates the proliferation, survival and diffusion of tumor cells, and further shapes the tumor microenvironment, thus affecting the tumor growth and transformation to a certain extent. Studies show that the new numbers of IL-12 family, IL-35, IL-39 and IL-27, play the relevant specific immune functions in a variety of tumors, which may be important target molecules for tumors research.

Objective:To investigate the clinical value of Octreotide plus Ulinastatin in the treatment of severe acute pancreatitis(SAP)in elderly patients.Methods:From May 2016 to February 2019, 124 elderly SAP patients admitted to the gastroenterology department of our hospital were enrolled and divided into the combination therapy group and the control group, with 62 patients in each group.The combination therapy group was treated with Octreotide and Ulinastatin, while the control group was treated with Octreotide alone.Serum leukocyte count, C-reactive protein(CRP), interleukin(IL)-6, tumor necrosis factor(TNF)-α and amylase levels were monitored before and 1, 3, 5, 7 and 14 days after treatment by automated biochemical analysis and enzyme-linked immunosorbent assays.The pain grade scale, APACHE-Ⅱ score and efficacy evaluation were analyzed for the two groups 7 days after treatment.The time to oral refeeding and length of hospitalization were compared between the two groups, and related complications during the treatment were recorded.Complications and the recurrence of pancreatitis within 1 year were followed up in both groups.Results:There was no statistically significant difference in serum white blood cell count, CRP, amylase, IL-6 and TNF-α levels between the two groups before treatment(all P>0.05). Serum white blood cell count, CRP and TNF-α levels had significant differences( t=3.735, 2.851 and -2.147, P=0.036, 0.029 and 0.043)and serum amylase and IL-6 levels had no significant difference( P>0.05)between the two groups 3 days after treatment.All the above parameters had significant differences between the two groups 7 days after treatment( t=3.624, 2.918, -2.166, 2.684 and -2.593, P=0.023, 0.011, <0.001, 0.015 and <0.001). Serum amylase, IL-6 and TNF-α levels had significant differences( t=-3.515, 4.627 and -3.189, all P<0.001)and serum white blood cell count and CRP had no significant difference(all P>0.05)between the two groups 14 days after treatment.There were significant differences in visual analogue scale(VAS)and APACHE-Ⅱ score between the two groups 7 days after treatment( t=-2.346 and -3.245, P=0.021 and 0.002). On the 7th day after treatment, the effectiveness rate was 79.0%(49/62)in the combination therapy group and 61.3%(38/62)in the control group, with a significant difference between the two groups( χ2=4.661, P=0.031). Compared with the control group, time to oral refeeding and hospitalization length were shorter in the combination therapy group than in the control group(6.72±1.87 d vs.7.65±1.69 d, 11.23±2.98 d vs.13.85±3.42 d, t=-2.868 and -4.565, both P<0.05). There were significant differences in the incidences of infectious pancreatic necrosis, gastrointestinal adverse reactions and organ failure between the combination therapy group and the control group(11.3% or 7/62 vs.25.8% or 16/62, 43.5% or 27/62 vs.21.0% or 13/62, 1.6% or 1/62 vs.11.3% or 7/62, χ2=4.324, 7.233 and 4.810, P=0.038, 0.007 and 0.028). There were significant differences in mean length of time without complications and recurrence between the combined group and the control group(10.25±3.26 months vs.8.72±3.73 months, 10.69±2.51 months vs.9.62±2.92 months, Log Rank χ2=7.463 and 4.589, P=0.006 and 0.032). Conclusions:Octreotide combined with Ulinastatin can effectively alleviate local symptoms, slow clinical progression, reduce the risk of complications, decrease the recurrence rate and promote early recovery in elderly SAP patients.

Objective: To compare the effects of Jinghua Weikang capsule and bismuth potassium citrate in the treatment of Helicobacter pylori(Hp) infection. Methods: From July 2016 to April 2018, 124 patients who were diagnosed as Hp positive by gastrointestinal urease test and 13C breath test at the First Affiliated Hospital of He'nan University were randomly divided into group A(63 cases) and group B(61 cases) according to the digital table.Group A received bismuth potassium citrate + standard triple therapy, treatment for 14 days.Group B was given Jinghua Weikang capsule+ standard triple therapy, treatment for 14 days.One month after treatment, the treatment effect of the two regimens was recorded. Results: The total effective rates of group A and group B after one course of treatment were 88.89%(56/63) and 93.44%(57/61), respectively, the difference was no statistically significant between the two groups(χ²=0.795, P=0.373). The Hp eradication rates of group A and group B were 84.13%(53/63) and 95.08%(58/61), respectively, the difference was statistically significant(χ²=3.963, P=0.047). The proportions of patients with improved symptoms within 7 days in group A and group B were 68.25%(43/63) and 83.61%(51/61), respectively, the difference was statistically significant(χ²=3.983, P=0.046). The incidences of adverse reactions in group A and group B were 14.29%(9/63) and 3.28%(2/61), respectively, the difference was statistically significant(χ²=4.645, P=0.031). Conclusion Compared with bismuth potassium citrate, Jinghua Weikang capsule has similar clinical effect after one course of treatment, higher Hp eradication rate, lower incidence of adverse reactions, faster symptom improvement, and the satisfaction and compliance of patients are higher.

BACKGROUND:Currently, there are few researches on the effect of punicalagin on the formation and differentiation of osteoclasts, and fewer researches on the mechanism of bone resorption diseases induced by wear particles. OBJECTIVE: To establish a model of titanium particles induced mouse monocyte/macrophage cel line (RAW264.7) differentiating into osteoclasts and to observe the effect of different concentrations of punicalagins on osteoclast proliferation and differentiation. METHODS: Mouse monocyte/macrophage cel lines (RAW264.7) were divided into five groups, cultured in the culture medium of common (blank group), 0.1 g/L titanium particle suspension, 0.1 g/L titanium particle suspension with 25 μmol/L punicalagins, 0.1 g/L titanium particle suspension with 50 μmol/L punicalagins, 0.1 g/L titanium particle suspension with 100 μmol/L punicalagins, respectively. The cel proliferative activity was detected by cel counting kit-8 assay at 1, 3 and 5 days. At 5 days after culture, number of osteoclasts was measured by tartrate-resistant acid phosphatase staining, the phosphorylation of IκBα and NF-κB p65 was detected by western blot assay, the mRNA expressions of nuclear factor of activated Tc1, tartrate-resistant acid phosphatase and matrix metaloproteinase-9 were measured by reverse transcription-PCR. RESULTS AND CONCLUSION:Compared with control group, titanium particles and different concentrations of punicalagin had no effect on the proliferation of RAW264.7 cels (P > 0.05). The number of tartrate-resistant acid phosphatase staining -positive cels, the phosphorylation of IκBα and NF-κB p65 as wel as the mRNA expressions of nuclear factor of activated Tc1, tartrate-resistant acid phosphatase and matrix metaloproteinase-9 were significantly increased compared with those of control group (P < 0.05,P < 0.01). And punicalagins in a concentration-dependent manner decreased the expression of the above indicators. These results indicate that punicalagin can inhibit osteoclast formation and differentiation.