Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective: Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). Materials and Methods: This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15–27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. Results: During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975–97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025–3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810–9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. Conclusion Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

Clear cell renal cell carcinoma (ccRCC) has been proved to be a metabolic disease with high

Optimization efforts were devoted to discover novel PDE10A inhibitors in order to improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension (PAH) starting from the previously synthesized inhibitor

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

OBJECTIVE: To evaluate the outcomes and to find out the influence factors of indirect pulp treatment in primary teeth. METHODS: Children who received indirect pulp treatment in primary teeth in the Department of Pediatric Dentistry in Peking University School and Hospital of Stomatology from August, 2014 to September, 2016 were collected in the Electronic Medical Record Database of Peking University School and Hospital of Stomatology, via the database for scientific research provided by the corporation of Kaientai. The children selected as the subjects of this study were followed up over 1.5 years, and they were under 9 years old if in the group of primary molars while the children in the group of primary anterior teeth were under 4 and a half years old. Those children who were not reviewed regularly or didn't have complete medical records were removed. Basic information, the relevant medical records and radiographic records of those children were collected. All teeth were examined clinically and classified into 2 outcomes, teeth in group H were regarded as succeeded, and teeth in group P were regarded as failed. Survival analysis was applied. The survival rate and survival time of the deciduous teeth calculated. Multivariate analysis was performed by using Cox proportional hazard model. RESULTS: One hundred and six children were finally included, aged from 1.6 to 8.8 years, with the mean age of (5.0±1.7) years. 168 primary teeth (122 primary molars, 46 primary anterior teeth) were included, and the average follow up time was (729±244) days. Thirty-five primary teeth (23 primary molars, 12 primary anterior teeth) failed upon clinical or radiographic examinations by September, 2018. The cumulative survival probability of half a year, one year, one year and a half, two years, two and a half years for the indirect pulp treatment was 93.5%, 92.9%, 87.5%, 82.7%, and 75.5% through the KaplanMeier method, respectively. Through the analysis of Cox proportional hazard model, in primary molars, the survival probability tended to be lower when the number of tooth surface affected by caries was greater (OR=1.709, P<0.05). Compared with primary molars, the survival probability of primary anterior teeth was lower, but the difference was not significant. CONCLUSION Complying the current instructions in our department, the cumulative survival probability of two and a half years after the indirect pulp treatment in primary teeth was 75.5%. In primary molars, the survival probability tended to be lower when the number of tooth surfaces affected by caries increased.
Child ; Child, Preschool ; Dental Caries ; Dental Pulp ; Humans ; Infant ; Molar ; Retrospective Studies ; Tooth, Deciduous

OBJECTIVE: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. METHODS: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. RESULTS: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P<0.001). Participants with "moderate" or "good" social health had a significantly lower risk of depressive symptoms than those with "poor" social health (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.46-0.66 for moderate social health; OR=0.45, 95% CI: 0.35-0.60 for good social health). The association between social health and depressive symptoms was consistent across several subgroups. CONCLUSIONS Social health is significantly inversely associated with depressive symptoms. The SHSE may serve as an efficient screener to identify those elderly adults with social health deficits, but systematic assessment to guide intervention merits further investigation.
Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Depression/epidemiology* ; Female ; Health Status ; Humans ; Independent Living ; Logistic Models ; Male ; Middle Aged

BACKGROUNDDespite extensive research, the mechanism of immature dendritic cells (DCs) induced immune hyporesponsiveness remains incompletely understood.

METHODSRecipient DCs from C3H mouse bone marrow cells were incubated with donor antigen from splenic lymphocytes of C57BL/6 mouse; these DCs were transfected with CD80/86 specific siRNA using lentiviral vectors. Flow cytometry was used to evaluate expression of CD80/86 on the antigen-pulsed recipient DCs. Immune regulatory activity was examined by mixed lymphocyte reaction, in which irradiated DCs were cultured with C3H spleen T cells. After the reaction, interleukin (IL)-2, IL-4, IL-10, and interferon (INF)-γ levels of mixed lymphocyte reaction culture supernatant were measured by enzyme-linked immunosorbent assay. The apoptotic T lymphocytes were identified by Annexin V and CD3 staining.

RESULTSThere was a significant inhibition of CD80/86 expression in DCs transfected with CD80/86 lentiviral vectors compared with the control groups (P < 0.05), indicating the specificity of RNA interference. Enzyme-linked immunosorbent assay results showed a significant reduction of INF-γ, IL-2 and IL-10 in the CD80/86 lentivirus transfected group compared to the control groups (P < 0.05). There was no significant difference in IL-4 levels between the groups (P > 0.05). We also showed that CD80/86 low DCs loaded with alloantigen (1) stimulated low T cell proliferative responses via the indirect recognition pathway and (2) enhanced apoptotic activity (P < 0.05) in co-cultured T cells.

CONCLUSIONSLentiviral vector transfection can effectively and specifically knock down target genes in DCs. The CD80/86 low DCs may show tolerogenic activity via induction of T-cell apoptosis, thereby modulating the activity of recipient-derived DCs. The use of this approach may potentially be clinically applicable.

Animals ; Apoptosis ; B7-1 Antigen ; genetics ; physiology ; B7-2 Antigen ; genetics ; physiology ; Dendritic Cells ; immunology ; Lentivirus ; genetics ; Lymphocyte Activation ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; RNA Interference ; T-Lymphocytes ; cytology ; immunology

Objective To investigate the relationship and the influence between pre-diabetes mellitus (PDM) and hyperuricemia (HUA).Methods 157 PDM patients,aged 20 to 75 years old were selected from the Second Clinical Medical College of Harbin Medical University,from 2009 February to 2010 February and were divided into HUA group (76 cases) and NUA group (81 cases).All the patients had not been on thiazide drugs.T-test and Pearson correlation analysis were used to calculate the differences and correlation between uric acid and biochemical indicators.Results In the HUA group,BMI was (27.74 ± 2.88) kg/m2,waist to height ratio (WSR) was (0.55 ± 0.41),TC was (6.61 ± 0.73) mmol/L,TG was (3.94 ± 1.97) mmol/L,LDL-C was (3.60 ± 0.45) mmol/L and homeostasis model assessment-insulin resistance index (HOMA-IR) was (3.09± 1.20).There were significant differences noticed in BMI,TG,TC,LDL-C,HOMA-IR at higher level in the HUA group than those in the NUA group.Pre-diabetes uric acid levels were positively correlated with TG,TC,LDL-C while HOMA-1R (TG:r=0.29,TC:r=0.33,LDL-C:r=0.49,HOMA-IR:r=0.51,P＜0.05)was negatively correlated (r=－0.30,P＜0.05) with the HbAlc.Conclusion The levels of PDM uric acid might both be related with TC,TG,LDL-C and HOMA-IR.The High level of uric acid status in vivo appeared closely related to HOMA-IR,which could further promote the progress of pre-diabetic patients to diabetes and causing dyslipidemia.Our findings suggested that the levels of pre-diabetes uric acid levels should be under concern.