Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.

Objective:To evaluate the effectiveness and safety of coronavirus disease 2019 (COVID-19) vaccines for dialysis patients with chronic kidney disease.Methods:PubMed, Medline, Embase databases and CNKI, VIP, Wanfang databases were searched systematically. The deadline was April 25, 2022. The search terms included haemodialysis, peritoneal dialysis, vaccine, seroresponse, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main outcome included the positive rate after vaccination, antibody titer, antibody changes during follow-up, infection rate of SARS-CoV-2, hospitalization rate and mortality.Results:A total of 154 195 patients were analyzed in 26 studies. The results of meta-analysis showed that the positive rate of serum IgG antibody in patients with chronic kidney disease was 48% after the first dose of vaccine, 89% and 96% after the second dose and third dose, respectively. After vaccination with COVID-19 vaccines, there was no significant difference in serum antibody and titer between hemodialysis patients and peritoneal dialysis patients. However, compared with the healthy control group, the antibody positive rate and antibody titer of dialysis patients after vaccination were lower (both P<0.05). In the follow-up, the antibody positive rate at the third month decreased by 12% compared with at the first month, at the sixth month decreased by 15% compared with at the third month, and at the sixth month decreased by 20% compared with at the first month. The serum antibody positive rate after the third dose of vaccine increased by 38% ( RR=1.38, 95% CI 1.12-1.70, P<0.001), and the antibody titer increased significantly ( SMD=1.46, 95% CI 0.31-2.61, P<0.001). Although the vaccines could not reduce the infection rate of SARS-CoV-2 in dialysis patients, it could significantly reduce the hospitalization rate and mortality after infection. Conclusions:After vaccination with COVID-19 vaccines, dialysis patients can produce strong serum antibodies, which can reduce the hospitalization rate and mortality after SARS-CoV-2 infection. However, the duration of antibody is short and the titer level is low, so it is necessary to timely vaccinate booster vaccine dose to obtain stronger immunogenicity.

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound

Most patients with schizophrenia have experienced a period called clinical high risk (CHR) preceding the first episode of psychosis.Early identification of CHR and timely medication or psychological intervention may reduce conversion to psychosis.By exploring biomarkers that predict the onset of psychosis and improving the accuracy of predicting the prognosis of CHR state, it is possible to take a more active intervention measure.As a fast and economical neurophysiological test, event-related potential (ERP) may reflect the perception process, pre-attention process, and attention distribution of the cognitive processes.And it holds promise for becoming objective indices in predicting the clinical outcomes of the CHR patients.This paper reviews the current studies on different ERP components in the CHR population and their performance as predictors of clinical outcomes.The results show that among ERP abnormalities, P300 and MMN amplitude reductions appear to be more reliable than others, which may indicate that distinct components reflect different stages of the disease.However, as a physiological index in the CHR group, aberrant ERP lacks certain specificity.The algorithm analysis combining different ERP components or combining components with symptoms may make the test more specific in the future.

Objective To observe the role of community popular opinion leader (POL) intervention on ocular epidemic study. Methods During the process of epidemiological survey of eye disease in Shenyang City,the community POL was interviewed to observe the change of the follow-up population from 2015 to 2016 and the effects of the POL intervention were analyzed. Results The study population follow-up rate was significantly improved after POL intervention (χ2 = 85.42,P < 0.01),the male-to-female ratio was balanced (χ2 = 6.51, P = 0.01),and more participants were willing and hoped to participate in the epidemic study for a long time. Conclusion Community POLs can improve the follow-up rate of epidemiological surveys and mobilize the enthusiasm of the population to participate in epidemiological investigations.

The mode of community home-based care with combination of medical care and elderly care is im-portant for promoting healthy aging. But now the services contents provided by community health service agencies were not clear, related system of policies and regulations were imperfect, human resources were insufficient and net-work of service resource was not perfect. All of these factors caused the service cannot met old people medical de-mands and the use for community health services is inadequate. So we should proposesupply-side reform on communi-ty health service to meet the medical demands for old people and even to stimulate new demand.

Objective To evaluate the performance of different GFR equations in estimating renal function of people undertake health examination.Methods A total of 8 476 occupational physical examination population were selected.Serum creatinine,urea nitrogen,serum cystatin and urine routine of all cases were collected to be used to calculate eGFR through different GFR equations of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)equation.,the equation based on cystatin C(Cys-EPI),the combined creatinine-cystatin C equation(CC-EPI),simplified MDRD equtation (a-MDRD),modified eGFR equation for Chinese pa-tients (c-MDRD).Results There was a significant correlation among physical examination population using different GFR equa-tions calculated results(P <0.01).But comparisons the means of eGFR calculated by different equations are statistical significant (P <0.01).Comparing with CKD-EPI,the eGFR calculated by c-MDRD is higher(P =8.7×10-263 ).The ratios of population,eG-FR<60 mL·min-1 ·1.73(m2 )-1 by different equations,have significant difference (P <0.01).And the ratio difference is more concentrated in the range Of 45-59 mL·min-1 ·1.73(m2 )-1 .Devide the populations into two groups,which are chronic kidney disease (CKD)and Non-CKD according to the standard of eGFR and Urine protein by CKD-EPI.Among CKD,the eGFR calculated by Cys-EPI,CC-EPI,c-MDRD are higher;but among non-CKD group,eGFR calculated by Cys-EPI,a-MDR are lower,the eGFR of c-MDRD is significantly higher,while the result of CC-EPI is most close to the CKD-EPI.Conclusion There were significant corre-lations between the different equations to calculate GFR among physical examination population.

To explore novel non-opioid analgesic agents, 16 compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. YX0611-1 was treated as the leading compound. The results of mice writhing model and hot plate model showed that compounds 2, 7, 8, 9, 11 and 15 had obvious analgesic activities in vivo. The test of affinity to mu, delta, kappa receptor displayed that active compounds didn't act on opioid receptor. The results of preliminary toxicity and pharmacokinetic tests showed that compound 7 had better safety and pharmacokinetic properties than that of YX0611-1, and it deserved further development.

Objective To examine the polymorphism in NPHS2 gene of IgA nephropathy in northern Chinese patients and to investigate the possible association of the NPHS2 polymorphism with the development of IgA nephropathy, as well as its clinical and histologic manifestations.Methods The polymorphism of NPHS2 was analyzed by direct DNA sequencing in 32 northern Chinese patients with IgA nephropathy (16 with heavy proteinuria and 16 with isolated hematuria).According to preliminary results, a total of 537 IgA nephropathy patients were genotyped for the NPHS2 C357T polymorphism by PCR combined with restriction fragment length polymorphism (PCR-RFLP). We collected clinical and histologic manifestations for gene analysis in patients with IgA nephropathy, such as age, sex, urine protein excretion and so on.ResultsEight NPHS2 polymorphisms (-931A＞T, -601C ＞T, 19G＞T, 171A＞G, 357C ＞ T, IVS3-21C ＞ T, 1023C ＞ T and 1107A ＞ G) were identified.The preliminary results of gene sequencing showed that the frequency of 357T allele in nephrotic syndrome group was obviously lower than isolated hematuria group (0.038 vs 0.125, P ＜0.05).In 537 IgA nephropathy patients with clinical and histologic data, the average urinary protein excretion in the patients with the 357CT/TT genotype was less (P =0.023).The incidence of urinary protein of more than 3.5 g/d was significantly lower in patients with T allele and TT/CT genotype, respectively (P =0.017 and 0.011).The logistic regression analysis indicated that, even after adjusting for the effect of hypertension and age of patients, the CT/II genotype of NPHS2 C357T was an independent protective factor for the urinary protein excretion more than 3.5 g/d(P =0.012,OR = 0.485, 95％ CI 0.275-0.84).ConclusionsEight NPHS2 polymorphisms were identified in northern Chinese IgA nephropathy patients. The frequencies of NPHS2 T allele and TT/CT genotype were the protective factors for urinary protein, especially with that of more than 3.5 g/d.