Multiple sclerosis(MS)is a systemic inflammatory illness of the central nervous system that involves demyelinating lesions in the myelin-rich white matter and pathology in the grey matter.Despite signifi-cant advancements in drug research for MS,the dis-ease's complex pathophysiology makes it difficult to treat the progressive forms of the disease.In this study,we identified a natural flavonoid compound icariin(ICA)as a potent effective agent for MS in ameliorating the deterioration of symptoms including the neurological defi-cit score and the body weight in a murine experimental autoimmune encephalomyelitis(EAE)model.These improvements were associated with decreased demyelin-ation in the corpus callosum and neuron loss in the hippo-campus and cortex confirmed by immunohistochemistry analysis.Meanwhile,it was observed that the activation of microglia in cerebral cortex and hippocampus were inhibited followed by the neuroinflammatory cytokines downregulation such as IL-1β,IL-6 and TNF-α after ICA treatment,which was probably attributable to the sup-pression of microglial NLRP3 inflammasome activation.Additionally,molecular docking also revealed the binding force of ICA to NLRP3 inflammasome protein complexes in vitro.Taken together,our findings have demonstrated that ICA,as pleiotropic agent,prevents EAE-induced MS by improving demyelination and neuron loss,which inter-feres with the neuroinflammation via microglial NLRP3 inflammasome activation.

Objective: To investigate the association between adherens junction proteins E-cadherin and β-catenin and tight junction protein claudin-2 and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome (IBS-D). Methods: Cecal biopsy tissues were collected from IBS-D patients (n=26) according to Rome Ⅲ criterion and healthy controls (n=26). The duration of symptoms, abdominal pain score and mean weekly bowel movements were recorded. Colorectal dilatation combined with restraint stress were applied to establish visceral hypersensitivity rat model. Abdominal contraction reflex (AWR) was applied to assess the visceral sensitivity in rats. The stool frequency within 1 hour was recorded after establishing the rat model. The expression of E-cadherin、β-catenin and claudin-2 were assessed by Western blot and immunofluorescence microscopy. Intercellular ultrastructure was observed by transmission electron microscopy. Results: Compared with the healthy controls, the protein expression of E-cadherin and β-catenin in cecal epithelium in IBS-D patients were significantly lower (P=0.015 and P=0.005, respectively), while claudin-2 was significantly higher (P=0.000). Reduced E-cadherin and β-catenin expression was associated high abdominal pain score (r=-0.463, P=0.017 and r=-0.407, P=0.039). The lower expression of β-catenin was associated with longer duration of symptoms (r=-0.458, P=0.019). The protein expression of E-cadherin and ß-catenin in the cecal epithelium of the visceral hypersensitivity rats were significantly lower (P=0.004 and P=0.003, respectively), while claudin-2 was significantly higher (P=0.008). Reduced E-cadherin and ß-catenin expression was associated high visceral sensitivity in IBS-D rats (r=-0.639, P=0.047 and r=-0.888, P=0.001). Conclusions Intercellular ultrastructure alterations well as cecal β-catenin and E-cadherin protein expression decrease and are associated with high abdominal pain score in IBS-D patients and hypersensitivity rats. β-catenin is further associated with prolonged duration of symptoms in IBS-D patients. The expression of E-cadherin and β-catenin may play a vital role in visceral sensitivity and intestinal barrier dysfunction in IBS-D.

AIM: To evaluate the pharmacokinetics and bioequivalence of cetirizine hydrochloride tablets under fasting and fed conditions in Chinese healthy subjects. METHODS: This was a randomized, open-label, double-sequence, two-period, crossover designed study, and healthy subjects enrolled and administrated a single dose of 10 mg test and reference cetirizine hydrochloride tablets in each period under fasting or fed condition. The plasma concentrations of cetirizine were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated with WinNonlin 6.3 and the bioequivalence was evaluated through SAS 9.4 software. RESULTS: In the fasting condition, the major pharmacokinetic parameters of cetirizine of test and reference formulations were as follows, C

Objective: To explore the relationship between eHealth literacy and social support and depressive symptoms in female nursing students, and to provide a reference for improving the mental health of female nursing students. Methods: In November 2019, 1 115 female nursing students from freshmen to junior years in four medical colleges in Changsha were investigated eHealth Literacy Scale, Perceived Social Support Scale, Center for Epidemiological Studies Depression Scales and demographic information questionnaire. Results: The detection rate of depressive symptoms in female nursing students was 20.1%(224/1 115), and the qualification rate of eHealth literacy was 29.2%(326/1 115). The incidence of depressive symptoms were higher in female nursing students with urban household registration and their parents with high school education and above and poor family economic status(χ2=9.46, 20.02, 7.16, 12.40, P<0.05). Multivariate Logistic regression analysis showed that poor eHealth literacy and low social support were positively correlated with depressive symptoms in female nursing students(OR=3.16, 3.65, P<0.05). There was a correlation between the interaction of eHealth literacy and social support with depressive symptoms. In the same type of social support, the lower eHealth literacy level, the greater the risk of depressive symptoms was for female nursing students(P<0.05). Conclusion Health literacy and social support are the influencing factors of depressive symptoms in female nursing students. The occurrence of depressive symptoms can be reduced by improving the level of electronic health literacy and social support.

OBJECTIVE： To put forward the suggestions for improving drug management in clinical drug trials in China. METHODS： “Good clinical practice” “Clinical trials drug” “Drugs for clinical trials” “GCP” “Investigational drug products” as search terms， searching CNKI database， Wanfang database， PubMed database and OVID electronic journal full-text database during Jul. 2014-Jul. 2018. The differences of drug management guidelines and management systems （including management model， staffing and budget evaluation） in clinical drugs between China and the United States were summarized. The suggestions were put forward to the shortage of drugs management of clinical trials in China. RESULTS & CONCLUSIONS： A total of 154 literatures were retrieved， including 33 valid literatures. The guidelines for drug management in clinical trials in the United States were relatively perfect， such as the Guidelines for Drug Management in Clinical Trials promulgated by the American Society of Hospital Pharmacists， while China had not yet published such national guidelines. The drug management in clinical trials in the United States had two modes which is the management of part-time pharmacists in hospital pharmacy department and the management of several full-time pharmacists and pharmacy technicians. Pharmacists or pharmaceutical technicians participated in the whole process of management， and a lot of research was carried out on the budget evaluation of clinical trials drug management. Domestic clinical trials drug management included three modes which is full-time pharmacist management， full-time pharmacist and part-time nurse management， part-time pharmacist and part-time nurse management. Pharmacists and nurses jointly participated in the management， but the whole process management had not yet been achieved， and there were few studies on budget evaluation of clinical trials drug management. It is suggested that the management of clinical trials drug in China can improve the management efficiency and level of clinical trials drug by refining the management system of clinical trials drug， standardizing the management mode of clinical trials drug and carrying out management budget evaluation.

Objective To observe the changes of brain neurotransmitters in patients with vasovagal syncope (VVS) with encephalofluc-tuogram technology (ET). Methods From August, 2015 to December, 2016, 30 patients with VVS were selected as case group, 30 controls matched with sex and age were selected from the outpatients without syncope. They were detected the function of gamma aminobutyric acid (GABA), glutamate (Glu), 5-hydroxytryptamine (5-HT), acetylcholine (Ach), norepinephrine (NE) and dopamine (DA) with ET. Results There was no significant difference between the two groups in the values of GABA, Glu, 5-HT, Ach and DA (t<1.680, P>0.05), while the values of NE was higher in the case group than in the control group (t=-3.552, P<0.001). Conclusion VVS may be related to the high level of activity of NE in the brain.

Objective To investigate the promoting effect of individualized intervention on social function rehabilitation in patients with schizophrenia. Methods Total of 200 hospitalized patients with schizophrenia in a tertiary psychiatrichospital were selected as the research object and were randomly assigned to the study group ( n=100) and the control group ( n=100) . Patients in control group were treated with routine treatment and nursing, whilepatients in study group were given individualized intervention combined with routine treatment and nursing. Brief psychiatric rating scale ( BPRS) was used to assess the severity of the psychotic symptoms.Insight and treatment attitude questionnaire ( ITAQ) was used to assess the treatment compliance of patients. Activity of daily living scale (ADL) and personal and social performance scale(PSP) were used to assess their social function. Then, we compared the results of two groups that before and after the intervention. Results Before the intervention, there was no significant difference in BPRS, ITAQ and ADL scores between two groups ( P>0.05) . The PSP scores of the study group were lower than those of the control group ( P<0.05) . After the intervention, the ITAQ and PSP scores of two groups were significantly higher than those before the intervention, and the BPRS and ADL scores were significantly lower than those before the intervention ( P<0.05) . After the intervention, there was no significant difference in BPRS and ITAQ scores between two groups ( P>0. 05) . The ADL scores of the study group were significantly lower than those of the control group, and the PSP scores were significantly higher than those of the control group (P<0.05).Conclusions Personalized intervention enhances the patient′s self-care ability, daily activities ability and social competence, and promotes the recovery of social function.

Objective To investigate the expression of corticotropin-releasing factor (CRF) and its receptors including CRFR1 and CRFR2 on mouse mesenteric lymph nodes dendritic cells (MLNDC), and to analyze their effects on the biological phenotypes of intestinal dendritic cells .Methods The MLNDCs were isolated from C57BL/6 mice by using magnetic bead sorting .The purity of CD11c+DCs was identified by flow cytometry .The double-labeling immunofluorescence and the reverse transcriptase-polymerase chain reaction (RT-PCR) were performed to detect the expression of CRF , CRFR1 and CRFR2 on MLNDCs.The MLNDCs were exposed to CRF with or without the interference of CRFR 1 and CRFR2 antagonists .Flow cy-tometry was used to measure the changes of surface molecules ( MHCⅠ and MHCⅡ) and co-stimulatory molecules (CD80 and CD86).Results The CD11c+DCs accounted for (80.12±6.34)% of the isolate cells with a high cell viability of more than 90%.The expression of CRF , CRFR1 and CRFR2 at mRNA lev-el were detected in MLNDCs by RT-PCR.Results of the immunofluorescent staining assay indicated that both CRFR1 and CRFR2 were expressed on the surface of MLNDCs .The expression of CD86 on MLNDCs was inhibited by the treatment of MLNDCs with CRFR 1 antagonist , but enhanced by the treatment with CRFR2 antagonist .Conclusion Both CRF and CRFRs were detected in the MLNDCs isolated from the C57BL/6 mice.The CRF could alter the biological phenotypes of MLNDCs through binding to different CRFRs (CRFR1 and CRFR2), which affected the phenotypes of MLNDCs in opposite ways .

Objective To explore the safety and effectiveness of transurethral resection of the prostate (TURP) for large benign prostatic hyperplasia.Methods A total of 56 cases of patients with large benign prostatic hyperplasia were analyzed retrospectively.Results The weight of prostate tissue resected with TURP was 60.2 g (48-122 g).The resection rate was 60％,operation time 113.4 min (70-180 min).The lower urinary tract symptoms (LUTS) after TURP was improved significantly.The international prostate symptom scores (IPSS) of 38 cases were decreased from (25.6±1.5) before operation to (6.0± 2.0) after operation.The maximum urine flow rate were increased from (5.0±1.9) ml/s to (18.0±4.5) ml/s.The mean residual urine volume of 22 cases were reduced from 95 ml (40-250 ml) to 10 ml (0-60 ml).Conclusions Skilled TURP technology for large benign prostatic hyperplasia is a safe treatment with good effect and low complications rates.

Objective: To investigate the variation of γδ T cells from healthy human peripheral blood(PB)and neonatus cord blood (CB)in proliferation and subtypes with isopentenyl pyrophosphate(IPP), and to acquire enough γδ T cells possessing distinct characteristics for experimental study.Methods: Mononuclear-cells from peripheral blood and cord blood induced by IPP were stained separately with monoclonal antibodies,which were fluorescein-labeled,and then used for assaying the expressing condition of surfaco molecules,as well as to evaluate the variation of γδ T cells on the percentage, subtypes and pbenotypes by FCM.Results:γδ T cells only account for a small proportion in both PB and CB.However,there was a significant difference in the heterogeneity between peripheral blood and cord blood γδ T cells.Vγ9Vδ2 T cells were dominant in peripheral blood γδ T cells.Most of Vγ9Vδ2 T cells in fresh isolated PBMC were central memory-type(CD27~+ CD45RA~-)and effector memory-type(CD27~-CD45RA~-)with IPP, PB γδ T cells proliferated strongly;The effector memory-typo(CD27~-CD45RA~-)turned into the main subtype in all Vγ9Vδ2 T cells,and HLA-DR and B7 molecules were highly expressed on the populations.But the cord blood γδ T cells showed rather complex subgroup heterogeneity,and Vγ9Vδ2 T cells were almost na(i)ve-type(CD27~+ CD45RA~+); Though γδ T cells were expanded(the percent of γδ T cells was increased),and Vγ9Vδ2 T cells were differentiated towards central memory-type and effector memory-type on day 14 with IPP,most of γδ T celLs still remained in the phase of na(i)ve-type(CD27~+ CD45RA~+).Conclusion:Tbere lies great differences of γδ T cells in quantity and subtypes between healthy person peripheral blood and neonatus cord blood.Peripheral blood γδ T cells can be activated and proliferated with IPP, while cord blood γδ T cells have the potential to deferentiate into director memory-type which can be used for experimental and clinical study with the synergy of corresponding cytokines.The immuno-regulation and effector function will be reported in other papers.