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 cognition of both doctors and patients in the neurology department of a tertiary hospital in Linyi City regarding graded diagnosis and treatment,and to explore its influencing factors.Methods Convenient sampling was used to select 456 survey subjects from 20 medical institutions within the medical consortium of a tertiary hospital in Linyi City,including 191 medical staffs and 265 patients;A total of 35 medical staffs and patients were interviewed.Results The overall awareness of graded diagnosis and treatment among medical staff and patients was(3.731±0.563)points and(3.136±0.367)points,respectively.The influencing factors of medical staff on grading diagnosis and treatment are professional title,years of work experience,and hospital grade.The influencing factors of patient on grading diagnosis and treatment are age,type of medical insurance,average monthly income,and whether they had a transfer experience.Conclusion While strengthe-ning information technology construction,government supervision and investment,and enhancing the capacity building of grassro-ots medical institutions,it is also necessary to actively promote the construction of close medical consortia to accelerate the forma-tion of a standardized and orderly new system for medical treatment and diagnosis.

Objective To analyze the technical movement characteristics of female table tennis play-ers with shoulder impingement syndrome when hitting a forehand topspin loop ball,in order to explore the reasons for shoulder impingement syndrome.Methods Thirteen female table tennis athletes with shoulder impingement syndrome were recruited for the shoulder impingement group(age 20.31±2.56 years,height 165.69±4.00 cm,weight 56.62±6.00 kg)and 13 healthy female table tennis athletes(age 21.54±2.78 years,height 165.54±4.45 cm,weight 60.08±8.02 kg)were selected for the healthy group.Kinematic and electromyographic data of the upper limbs were collected during six tri-als of forehand topspin strokes using a three-dimensional motion capture system and a wireless surface electromyographic system.The data were then averaged and compared between the groups.Results The shoulder impingement group had a greater shoulder flexion angular velocity at the end of the forward swing compared to the healthy group(t=-3.689,P=0.001).In addition,the shoulder impingement group showed significantly smaller trunk torsion angular amplitude(t=2.614,P=0.015)and average an-gular velocity of trunk torsion(t=3.958,P=0.001).Furthermore,the peak activation level of the anteri-or serratus muscle was smaller in the shoulder impingement group compared to the healthy group(t=2.363,P=0.027).Finally,the deactivation duration of both the triceps brachii and brachioradialis mus-cles was shorter in the shoulder impingement group compared to the latter(t=3.705,P=0.002;t=3.29,P=0.004).Conclusion Female table tennis players with shoulder impingement syndrome exhibit the fol-lowing characteristics in their forehand topspin:1)insufficient trunk rotation and premature deactiva-tion of the brachioradialis muscle,which lead to excessive loading on the shoulder during flexion;2)inadequate activation of the serratus anterior muscle,resulting in compromised scapular stability;3)premature deactivation of the triceps brachii muscle,which negatively affects the control of eccentric contraction velocity at the shoulder joint.

Objective To analyze the technical movement characteristics of female table tennis play-ers with shoulder impingement syndrome when hitting a forehand topspin loop ball,in order to explore the reasons for shoulder impingement syndrome.Methods Thirteen female table tennis athletes with shoulder impingement syndrome were recruited for the shoulder impingement group(age 20.31±2.56 years,height 165.69±4.00 cm,weight 56.62±6.00 kg)and 13 healthy female table tennis athletes(age 21.54±2.78 years,height 165.54±4.45 cm,weight 60.08±8.02 kg)were selected for the healthy group.Kinematic and electromyographic data of the upper limbs were collected during six tri-als of forehand topspin strokes using a three-dimensional motion capture system and a wireless surface electromyographic system.The data were then averaged and compared between the groups.Results The shoulder impingement group had a greater shoulder flexion angular velocity at the end of the forward swing compared to the healthy group(t=-3.689,P=0.001).In addition,the shoulder impingement group showed significantly smaller trunk torsion angular amplitude(t=2.614,P=0.015)and average an-gular velocity of trunk torsion(t=3.958,P=0.001).Furthermore,the peak activation level of the anteri-or serratus muscle was smaller in the shoulder impingement group compared to the healthy group(t=2.363,P=0.027).Finally,the deactivation duration of both the triceps brachii and brachioradialis mus-cles was shorter in the shoulder impingement group compared to the latter(t=3.705,P=0.002;t=3.29,P=0.004).Conclusion Female table tennis players with shoulder impingement syndrome exhibit the fol-lowing characteristics in their forehand topspin:1)insufficient trunk rotation and premature deactiva-tion of the brachioradialis muscle,which lead to excessive loading on the shoulder during flexion;2)inadequate activation of the serratus anterior muscle,resulting in compromised scapular stability;3)premature deactivation of the triceps brachii muscle,which negatively affects the control of eccentric contraction velocity at the shoulder joint.

Objective To investigate the cognition of both doctors and patients in the neurology department of a tertiary hospital in Linyi City regarding graded diagnosis and treatment,and to explore its influencing factors.Methods Convenient sampling was used to select 456 survey subjects from 20 medical institutions within the medical consortium of a tertiary hospital in Linyi City,including 191 medical staffs and 265 patients;A total of 35 medical staffs and patients were interviewed.Results The overall awareness of graded diagnosis and treatment among medical staff and patients was(3.731±0.563)points and(3.136±0.367)points,respectively.The influencing factors of medical staff on grading diagnosis and treatment are professional title,years of work experience,and hospital grade.The influencing factors of patient on grading diagnosis and treatment are age,type of medical insurance,average monthly income,and whether they had a transfer experience.Conclusion While strengthe-ning information technology construction,government supervision and investment,and enhancing the capacity building of grassro-ots medical institutions,it is also necessary to actively promote the construction of close medical consortia to accelerate the forma-tion of a standardized and orderly new system for medical treatment and diagnosis.

The 2013 National Practitioners Qualification Examination Work Conference proposed to reform the traditional one-stop test into two stage. In May 2017, Fujian University of Traditional Chinese Medicine participated in this empirical study as a pilot for the first time. This paper made a preliminary summary and analysis of the results of the phased examination. Because of the absence and deficiency of clinical skills of students in our school, we carried out a series of reform measures for clinical skill courses: enhancing teaching facilities, enriching teaching contents and methods, reforming assessment mode and strengthening the monitoring of the teaching quality of clinical skills. According to the students, reform measures are conducive to consolidating theoretical knowledge and improving clinical skills, laying a good foundation for successfully passing the national examination of medical practitioners and becoming a qualified medical talent.

Objective To explore chromobox protein homolog 2 (CBX2) expressions in relation to clinical features of patients and elucidate its role in the progression of hepatocellular carcinoma.Methods Using the Cancer Genome Atlas (TCGA) database,R language was used to analyze the distribution of differentially expressed mRNA in hepatocellular carcinoma.The different expression of CBX2 in HCC and adjacent tissues and its relationship with survival and clinical characteristics of patients were further analyzed.The expression of CBX2 in liver tissues,liver cancer tissue,and L02,HepG2 and SMMC-7721 cell lines was detected by real time-PCR and western blot.The expression of CBX2 was interfered by siRNA in hepatoma cell line.MTT,colony formation,transwell assays,and flow cytometry were used to identify the proliferation,apoptosis,invasion and clone-formation ability of HepG2 and SMMC-7721 cells after CBX2 down-regulation.According to the different data,t-test,ANOVA,chi-square test,and COX regression model were used for statistical analysis.Survival curve was plotted through Kaplan-Meier method.Results TCGA public database analysis showed that the expression of CBX2 mRNA in hepatocellular carcinoma tissues (7.296 ± 1.6115) was significantly higher than normal liver tissues (4.706 ± 0.940) (P =0.000).In addition,the overall survival time of patients with low CBX2 mRNA expression was significantly longer than that of patients with high CBX2 mRNA expression [(5.971 ± 0.411) years vs.(4.650 ± 0.503) years,P =0.001].The expression level of CBX2 mRNA was correlated with the pathological TNM stage (P =0.025) and differentiation degree (P ＜ 0.001) of liver cancer.COX regression analysis showed that CBX2 mRNA expression was an independent predictor of patient survival (P =0.013).siRNA was transfected and compared with the blank control group.The transgenic ability of HepG2 and SMMC-77221 cells decreased significantly at 72h (P ＜ 0.05) and 96h (P ＜ 0.05),and the apoptosis rate (11.430％ ± 0.215％) was higher than blank control group (6.6 00％ ± 0.170％) (P =0.003).The number of invasive cells ((both P ＜ 0.05) and relative colony forming cells ((both P ＜ 0.001) were significantly decreased.In 20 cases of tissue samples,the expression of CBX2 protein (relative expression level 3.020 ±0.269) in liver cancer was higher than that in adjacent tissues (relative expression level 0.886±0.065) (P ＜ 0.001).The overall survival time of patients with low CBX2 expression in liver cancer was longer than that of patients with high expression [(3.670 + 0.576) years vs.(0.834 + 0.153) years,P =0.004].Conclusion An evident high expression of CBX2 is an independent poor prognostic factor in hepatoma.Down-regulation of CBX2 expression can inhibit the progression of liver cancer.Therefore,CBX2 may be a prognostic biomarker and a new target for HCC treatment.

Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.

Background and objective Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. hTe study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer. Methods Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by“classical”3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV) was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. hTe planning target volume (PTV) received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. hTe primary endpoints were acute toxicities. hTe secondary endpoints included overall survival (OS), pro-gression-free survival (PFS) and loco-regional failure-free survival (LRFFS) at 1-year of follow-up. Results Twenty men and six women were included. hTe median age was 52 (30-68) months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months), 1-year OS, PFS and LRFFS were 89.0%, 51.0%and 85.0%, respectively. Conclusion Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique.

Background and objective Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. hTis study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer. Methods Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. hTe pa-tients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). hTe primary end-points were hematologic toxicities during treatment. hTe secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was deifned as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity. Results From January 2013 to August 2016, 20 patients were enrolled in this study. hTe median age was 49.5 (30-68). Atfer the ifrst 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neu-tropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. hTe MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had≥Grade 3 neutropenia and 1 patients had≥Grade 3 acute esophagitis in Arm 1. 10 patients had≥Grade 3 neutropenia and no patient had≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91%and 61%, respectively. Conclusion hTe MTD of RT with concurrent chemotherapy of EP regi-men for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1).