Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Dendrobium is the largest genus of the Orchidaceae family.The fresh and dried stems of many species of this genus have been used as Shihu(Dendrobii Caulis)in traditional Chinese medicine,it is known as the foremost of the"Nine Great Herbs of China".Ancient texts highlight its uses for"strengthening yin,enhancing essence,nourishing the five viscera,alleviating fatigue,and dispelling skin heat and prickly heat".Modern research confirms that the polysaccharides and alkaloids it contains have antiviral ef-fects,it can apply in treating immunodeficiency caused by viral infections clinically.While studies are gradually uncovering the antivi-ral mechanisms and material basis of Dendrobium,the lack of systematic analysis and organization has hindered its resource develop-ment.The paper employed CiteSpace software for bibliometric analysis of Chinese and English literature on Dendrobium.It reviewed the herbalism,material basis,and mechanisms of its antiviral properties building upon the systematic review of ancient materia medica and modern literature.Results indicate that Dendrobium can boost vital energy and resist pathogens,showing great potential in antiviral drug development.

Dendrobium is the largest genus of the Orchidaceae family.The fresh and dried stems of many species of this genus have been used as Shihu(Dendrobii Caulis)in traditional Chinese medicine,it is known as the foremost of the"Nine Great Herbs of China".Ancient texts highlight its uses for"strengthening yin,enhancing essence,nourishing the five viscera,alleviating fatigue,and dispelling skin heat and prickly heat".Modern research confirms that the polysaccharides and alkaloids it contains have antiviral ef-fects,it can apply in treating immunodeficiency caused by viral infections clinically.While studies are gradually uncovering the antivi-ral mechanisms and material basis of Dendrobium,the lack of systematic analysis and organization has hindered its resource develop-ment.The paper employed CiteSpace software for bibliometric analysis of Chinese and English literature on Dendrobium.It reviewed the herbalism,material basis,and mechanisms of its antiviral properties building upon the systematic review of ancient materia medica and modern literature.Results indicate that Dendrobium can boost vital energy and resist pathogens,showing great potential in antiviral drug development.

Salivary gland tumor is one of the most common tumors in oral and maxillofacial regions.The diagnosis and treatment of salivary gland tumors had been a clinical characteristic project in Peking University School and Hospital of Stomatology since long time ago.Here we introduced the research pro-gress in diagnosis and treatment of salivary gland tumors during the past 10 years.Among 7 190 cases of salivary gland tumors treated in this institution,4 654 cases(64.7％)were benign,and 2 536(35.3％)were malignant,with benign:malignant ratio of 1.84∶1.Parotid was the most common loca-tion,followed by minor salivary gland and submandibular gland,while sublingular gland tumor was sel-dom seen.The proportion of minor salivary gland tumor was relatively high.Among 1 874 cases with pri-mary malignant tumors,the cases with T3 and stage Ⅲ accounted for only 9.6％and 10.3％,respec-tively,which indicated that there was shortcoming in the T classification and clinical stage formulated by Union for International Cancer Control(UICC),and further revision was required.The 5,10,and 15 year survival rates of 1 637 cases with postoperative follow-up were 93.1％,87.2％and 79.3％,respec-tively,which were much higher than those we reported 30 years ago.The improvement of treatment re-sults was related to more widely used combined treatment with surgery and postoperative radiotherapy,and the increase in patients with early stage.Adenoid cystic carcinoma was the malignant tumor with high rate of distant metastasis.The 5 and 10 year survival rates of the patients with pulmonary metastasis were 76.2％and 51.8％,respectively,which indicated that the pulmonary metastatic carcinomas developed slowly.Recurrent rate of carcinoma ex pleomorphic adenoma was 46.7％after single treatment of sur-gery,while it decreased to 27.5％after combined theraphy with surgery and radiotherapy,indicating that postoperative radiotheraphy could reduce the recurrent rate effectively.The normal myoepithelial cells had the inhibiting role in the invasion and metastasis of carcinoma ex pleomorphic adenoma.The evaluation of integrity of myoepithelial cells surrounding the tumor mass is helpful to understand the invasiveness of the tumors.The new surgical modalities such as extracapsular resection and partial sialoadenectomy were used in treatment of benign tumors of parotid gland and submandibular gland with advantages of decreased tissue damage and preservation of glandular function.Application of digital surgical techniques such as mixed reality combined with surgical navigation and real-time three-dimensional holograms in the surgical treatment of parotid gland tumors showed the benefits of more safety and precision,and less tissue da-mage.

Objective To investigate the effect and mechanism of microRNA-10b(miR-10b)on idiopathic short stature(ISS).Methods A total of 54 children with ISS and 54 healthy children were collected.The serum expression of miR-10b was detected by RT-qPCR,and the relationship between serum miR-10b expression and clinical data of children with ISS was analyzed.miR-10b inhibitor,si-TGFBR1 and their negative control transfection C28/I2 cells were used.CCK-8 experimental detection was used to detect C28/I2 cell proliferation.Western blot assay was used to detect gnome related transcription factor 2(RUNX2),collagen type X alpha 1 chain(COL10A1),transforming growth factor beta receptor 1(TGFBR1),SMAD3 and pSMAD3 protein expression.The target of miR-10b was screened in StarBase database,and the targeting relationship between miR-10b and TGFBR1 was verified by dual luciferase reporter gene assay.Results The serum expression of miR-10b was higher in the ISS group than that of the healthy control group,and the higher the miR-10b expression,the more obvious the decrease of child height,IGF-1 and alkaline phosphatase(P＜0.05).Compared with the NC group,the cell proliferation ability and RUNX2,COL10A1,TGFBR1,and pSMAD3 protein expression were up-regulated in the miR-10b inhibitor group(P＜0.05).StarBase database suggested that miR-10b had a binding site of TGFBR1,and dual luciferase reporter gene assay confirmed that TGFBR1 interacted with miR-10b(P＜0.05).Compared with the si-NC group,the expression of TGFBR1 was down-regulated and the cell proliferation ability was decreased in the si-TGFBR1 group(P＜0.05).Conclusion miR-10b inhibits chondrocyte proliferation and hypertrophy in idiopathic short stature by targeting TGFBR1/SMAD3 pathway.

To investigate the clinical features of esophageal neuroendocrine neoplasms (eNENs) and the role of endoscopic submucosal dissection (ESD) in the management of eNENs, clinicopathologic features and outcomes of 34 patients with eNENs (30 patients diagnosed by histopathology in the First Affiliated Hospital with Nanjing Medical University from January 2010 to December 2022 and 4 patients who underwent ESD reported in PubMed from January 2014 to December 2023) were retrospectively analyzed. Survival analysis was performed to identify prognostic factors of eNENs. The vulnerable patients of eNENs were elderly males (79.41%, 27/34) and the age of onset was 65.41±8.78 years. The lesions mostly occurred in the middle (41.18%, 14/34) and lower (41.18%, 14/34) esophagus. Dysphagia was the most common clinical manifestation, accounting for 58.82% (20/34). The median overall survival time was 36.31 months and the 1, 3, 5-year overall survival rate was 82.35%, 53.45% and 27.94% respectively. In the univariate analysis, the prognosis of eNENs varied in different location, size, stage and treatment strategies ( P<0.05). The primary tumor resection was an independent prognostic factor for the survival of eNENs in multivariate analysis ( P=0.041, HR=0.166, 95% CI: 0.030-0.927). The median survival time of the patients with primary tumor resection was significantly longer than that without resection (42.98 months VS 17.90 months, P=0.005). Whereas, there was no significant difference in median survival time between the patients who underwent surgical operation and those who underwent ESD (43.93 months VS 39.50 months, P=0.835). eNENs has no specific clinical manifestations. Resection of the primary tumor is a protective factor for the prognosis of eNENs. ESD has a comparable result to surgery and can be considered as a treatment modality for paticular patients.

To investigate the clinical features of esophageal neuroendocrine neoplasms (eNENs) and the role of endoscopic submucosal dissection (ESD) in the management of eNENs, clinicopathologic features and outcomes of 34 patients with eNENs (30 patients diagnosed by histopathology in the First Affiliated Hospital with Nanjing Medical University from January 2010 to December 2022 and 4 patients who underwent ESD reported in PubMed from January 2014 to December 2023) were retrospectively analyzed. Survival analysis was performed to identify prognostic factors of eNENs. The vulnerable patients of eNENs were elderly males (79.41%, 27/34) and the age of onset was 65.41±8.78 years. The lesions mostly occurred in the middle (41.18%, 14/34) and lower (41.18%, 14/34) esophagus. Dysphagia was the most common clinical manifestation, accounting for 58.82% (20/34). The median overall survival time was 36.31 months and the 1, 3, 5-year overall survival rate was 82.35%, 53.45% and 27.94% respectively. In the univariate analysis, the prognosis of eNENs varied in different location, size, stage and treatment strategies ( P<0.05). The primary tumor resection was an independent prognostic factor for the survival of eNENs in multivariate analysis ( P=0.041, HR=0.166, 95% CI: 0.030-0.927). The median survival time of the patients with primary tumor resection was significantly longer than that without resection (42.98 months VS 17.90 months, P=0.005). Whereas, there was no significant difference in median survival time between the patients who underwent surgical operation and those who underwent ESD (43.93 months VS 39.50 months, P=0.835). eNENs has no specific clinical manifestations. Resection of the primary tumor is a protective factor for the prognosis of eNENs. ESD has a comparable result to surgery and can be considered as a treatment modality for paticular patients.

Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 μIU per 106 sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 μIU per 106 sperm) and the group with low acrosin activity (<24.78 μIU per 106 sperm). The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 21.2%, while the group with a high IVF fertilization rate had a low index of 0.2%. At an acrosin activity of <24.78 µIU per 106 sperm, in one cycle of the same patient, the fertilization rate, normal fertilization rate, and good-quality embryo rate for ICSI were significantly higher than those for IVF. Therefore, the most promising application of acrosin activity could be in the selection of ICSI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.