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.

Objective:To investigate the perioperative efficacy of robot surgical system assisted anatomic and non-anatomic hepatectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinical data of 103 patients who underwent robot surgical system assisted hepatectomy in Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine from March 2016 to December 2021 were collected. There were 54 males and 49 females, aged 56(range, 44?64)years. Of the 103 patients, 55 cases undergoing robot surgical system assisted anatomic hepatectomy were divided into the anatomic group, and 48 cases undergoing robot surgical system assisted non-anatomic hepatectomy were divided into the non-anatomic group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Propensity score matching and compari-son of general data of patients between the two groups after matching. Of the 103 patients, 94 cases were successfully matched, including 47 cases in the anatomic group and 47 cases in the non-anatomic group. The elimination of preoperative body mass index, preoperative platelet and preoperative albumin confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative conditions. After propensity score matching, the operation time and volume of intraoperative blood loss were 175(range, 120?240)minutes and 50(range, 50?100)mL in patients of the anatomic group, versus 155(range, 105?190)minutes and 100(range, 50?200)mL in patients of the non-anatomic group, showing significant differences in the above indicators between the two groups ( Z=1.97, 2.49, P<0.05). (3) Perioperative complications. After propensity score matching, cases with pleural fluid and/or ascites, case with biliary fistula, case with thrombosis, case with peritoneal infection, case with incision infection were 11, 1, 2, 4, 1 in patients of the anatomic group, versus 12, 0, 4, 1, 0 in patients of the non-anatomic group, showing no significant difference in the above indicators between the two groups ( P>0.05). Cases with complications classified as grade Ⅰ, grade Ⅱ, grade Ⅲ, grade Ⅳ of the Clavien-Dindo classification were 33, 14, 0, 0 in patients of the anatomic group, versus 28, 14, 3, 2 in patients of the non-anatomic group, showing no significant difference in the above indicators between the two groups ( Z=?1.38, P>0.05). Conclusions:Robotic surgical system assisted anatomic and non-anatomic hepatectomy are safe and feasible for clinical application. Compared with robot surgical system assisted non-anatomic hepatectomy, patients under-going robot surgical system assisted anatomic hepatectomy have long operation time and less volume of intraoperative blood loss.

Objective:To systematically sort out and cluster the existing indicators of key issues in the quality of postgraduate clinical degree education based on the bibliometric study, so as to build a multidimensional quality assessment index system that integrates scientificity, rationality and representativeness, and to provide a scientific measurement tool for assessing clinical professional postgraduate education in China.Methods:By mining the related functions of UCINET6 network analysis integration software and its one-dimensional and two-dimensional data analysis NetDraw program, the social network analysis (SNA) method was used to extract and cluster the education quality problem set of clinical professional degree postgraduates.Results:A three-dimensional evaluation index system was constructed. The first dimension concluded such 8 key issues in the quality of postgraduate education in clinical medicine as ability assessment, teaching system, teaching quality assurance system, professional cognition and career prospects, assessment and evaluation system and organization, and the pulse taking and diagnosis.Conclusion:The clinical graduate education quality evaluation index system is an effective measurement tool for education quality improvement, based on a multidimensional perspective, with key issues as priority areas for intervention, providing an effective evidence-based basis for ensuring the development of professional graduate education efforts from 2020-2025.

Objective:To explore the correlations between circulating tumor cells (CTCs) level in peripheral venous blood and clinicopathological characteristics and biomarkers of lung cancer patients using CI-101 cell search immunomagnetic bead enrichment technology combined with fluorescent cytochemical staining.Methods:Blood samples were collected from 100 patients with first-diagnosed lung cancer treated in Department of Thoracic Surgery and Department of Cardiothoracic Surgery of Yunnan Cancer Hospital from March 2014 to September 2014, 40 patients with lung benign tumor (all confirmed by pathological biopsy) and 30 healthy volunteers from the physical examination center. CTCs in peripheral blood were enriched by CI-101 cell search immunomagnetic bead, the morphology of CTCs was analyzed by immunocytofluorescence technique, and tumor cells were identified using HE cell staining method. The recovery rate, sensitivity and specificity of CI-101 cell search instrument for CTCs were detected. The difference of positive rate of CTCs in peripheral blood among lung cancer patients, lung benign tumor patients and healthy volunteers was compared. The relationship between the positive rate of CTCs and the clinicopathological characteristics of patients with lung cancer was analyzed. The correlations between CTCs and serum tumor markers were analyzed by coefficient of contingency in patients with lung cancer and lung benign tumor.Results:The recovery rate of CTCs by CI-101 cell search instrument was 72.0%-89.0%, and there was a significant linear correlation between the number of recovered cells and the number of incorporated cells. The correlation coefficient r=0.998 ( P<0.001), the linear regression equation was y=0.781 x+ 11.307, the sensitivity was 85.0%, and the specificity was 71.4%. The positive rate of CTCs in lung cancer patients (85.0%, 85/100) was higher than that in lung benign tumor patients (15.0%, 6/40) and healthy volunteers (46.7%, 14/30) ( χ2=62.798, P<0.001). The positive rate of CTCs in lung cancer patients was correlated with TNM stage ( χ2=19.059, P<0.001), tumor size ( χ2=13.830, P<0.001) and distant metastasis ( χ2=6.005, P=0.014). Coefficient of contingency analysis showed that the positive of CTCs was positively correlated with serum tumor markers CEA ( φ=0.217, P=0.011), CA125 ( φ=0.198, P=0.020), CA199 ( φ=0.169, P=0.049), CA742 ( φ=0.186, P=0.037) and cytokeratin 19 fragment ( φ=0.461, P<0.001) in patients with lung cancer and lung benign tumor. Conclusion:The application of CI-101 cell search instrument combined with immunomagnetic bead method can successfully enrich CTCs in peripheral venous blood of lung cancer patients. The positive rate of CTCs in patients with lung cancer has obvious correlation with tumor size, TNM stage, distant metastasis, serum tumor markers. It can be used as an auxiliary indicator for monitoring the condition of lung cancer patients.

The incidence and mortality of lung cancer rank first, and small cell lung cancer (SCLC) accounts for about 15% of lung cancer cases. In recent years, it has been found that long non-coding RNA (lncRNA) (TUG1, CCAT2, PVT1, HOTTIP and HOTAIR) plays a significant role in the development of SCLC. lncRNA can regulate the expression of related genes at the transcriptional, posttranscriptional and epigenetic levels, and it can infulence proliferation, invasion, metastasis and chemotherapy resistance of SCLC.