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 explore the effect of intermittent fasting combined with diversified management mode on weight loss of overweight and obese people. Methods A total of 120 overweight and obese patients were selected as research objects, and randomly divided into control group (n=60) and experimental group (n=60). The control group was given intermittent fasting, and the experimental group was given diversified management mode on the basis of the control group. Waist circumference, body mass, body mass index (BMI), waist-to-hip ratio and blood lipid level were compared between the two groups; the scores of hunger, satiety, satisfaction and the incidence of adverse reactions were compared between the two groups. Results After intervention, waist circumference, body mass, BMI, waist-to-hip ratio, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the experimental group were significantly lower, and high-density lipoprotein cholesterol (HDL-C) was significantly higher than that in the control group (P < 0.05). After intervention, the hunger score of the experimental group was significantly lower, and the satiety score and satisfaction score were significantly higher than those of the control group (P < 0.05). The total incidence of adverse reactions in the experimental group was 6.67%, which was significantly lower than 20.00% in the control group (P < 0.05). Conclusion The application of intermittent fasting combined with diversified management mode in overweight and obese people is better, which can improve the relevant clinical indicators and blood lipid levels, and has high safety.

ObjectiveTo investigate the distribution and trend of rehabilitation personnel of China Disabled Persons' Federation (CDPF) system and the people with disabilities (PWDs) using geographical gravity model. MethodsBased on ArcGIS and statistical data, the distribution of geographical center of gravity of the rehabilitation personnel of the CDPF system from 2011 to 2021 was analyzed. According to the economic development, the areas were divided into three regions, and the eastern region included eleven provincial units, the central region includes eight provincial units, and the western region included twelve provincial units. ResultsCompared with 2011, rehabilitation staffs per thousand PWDs increased at 107.5% in 2021, 81.1%, 114.2% and 174.1% for the eastern, central, and western regions, respectively; professional staffs increased at 190.5%, 148.8%, 284.6% and 280.6% for the eastern, central, and western regions, respectively; managerial staff increased at 80.0%, 46.8%, 554.3% and 128.1% for the eastern, central, and western regions, respectively. Compared with 2011, the geographical center of gravity of the rehabilitation personnel moved about 330.9 km in 2021, while the geographical center of gravity of the PWDs moved about 169.64 km. ConclusionThe rehabilitation personnel in the CDPF system is the most in the eastern region and least in the western region. The tracks of the geographical center of gravity of the three kind of rehabilitation personnel in the CDPF system are relatively consistent. The rehabilitation personnel in the eastern region are more concentrated than those in the western region, and the density of the PWDs is more westward than that of the rehabilitation personnel, and coordination is not a perfect match yet. It is necessary to strengthen the rehabilitation personnel allocation in the western region, to balance distribution of human resources for rehabilitation of PWDs among regions.

Objective:To evaluate the influence of telomerase reverse transcriptase (TERT) promoter mutation on radioiodine uptake status of radioactive iodine refractory papillary thyroid cancer (RAIR-PTC) and radioiodine therapy response by analyzing the mutation frequency of TERT promoter in RAIR-PTC.Methods:A total of 37 patients with RAIR-PTC (15 males, 22 females, age (49.8±16.1) years) and 40 PTC patients with effective radioiodine therapy (13 males, 27 females, age (39.8±10.9) years) between January 2005 and June 2020 in JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine were retrospectively analyzed. TERT promoter mutation and B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation of patients were observed. The differences across genotype patterns on radioiodine uptake status and therapy response were compared. The Fisher′s exact test and independent-sample t test were used for data analysis. Results:The incidence rate of TERT promoter mutation in the RAIR-PTC group was 40.54% (15/37, all C228T), which was significantly higher than that in the effective radioiodine therapy group (0, 0/40; P<0.001). No statistically significant difference was found for the mutation rate of BRAF V600E between the RAIR group (64.86%, 24/37) and the effective radioiodine therapy group (72.50%, 29/40; P=0.858). Patients with TERT promoter mutation were older ( t=3.76, P=0.001) and the non-intake rate of radioiodine in distant metastases of those patients was higher ( P=0.037). Furthermore, 2/3 of patients who received targeted therapies and 3/4 deaths had TERT promoter mutation. Among 35 patients with negative thyroglobulin antibody (TgAb), 11/14 of patients with TERT mutation had a rising stimulated thyroglobulin (sTg), while the percentage of the non-TERT mutation group was 57.1% (12/21; P=0.357). Conclusion:The TERT promoter mutation rate is significantly increased in RAIR-PTC patients and can serve as a prognostic predictor in RAIR.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has had a massive impact on public health, resulting in sudden dietary and behavioral habit changes. Frontline epidemic prevention workers play a pivotal role against COVID-19. They must face high-risk infection conditions, insufficient anti-epidemic material supplies, mental pressure, and so on. COVID-19 seriously affects their dietary and behavioral habits, and poor habits make them more susceptible to COVID-19. However, their baseline dietary and behavioral habits before COVID-19 and their willingness to change these habits after the outbreak of COVID-19 remain unclear for these workers in China. This study aimed to explore the baseline dietary and behavioral habits of frontline workers and their willingness to change these habits after the outbreak of the epidemic; in addition, susceptible subgroups were identified by stratified analyses as targets of protective measures to keep them from being infected with COVID-19. METHODS: A cross-sectional study was conducted through an online questionnaire using a sample of 22,459 valid individuals living in China, including 9402 frontline epidemic prevention workers. RESULTS: Before COVID-19, 23.9% of the frontline epidemic prevention workers reported a high-salt diet, 46.9% of them reported a high frequency of fried foods intake, and 50.9% of them smoked cigarettes. After the outbreak of COVID-19, 34.6% of them expressed a willingness to reduce salt intake, and 43.7% of them wanted to reduce the frequency of pickled vegetables intake. A total of 37.9% of them expressed a willingness to decrease or quit smoking, and 44.5% of them wanted to increase sleep duration. Significant differences in the baseline dietary and behavioral habits and the willingness to change their habits were observed between frontline epidemic prevention workers and other participants. Among the frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19, frontline epidemic prevention experience was a promoting factor for adopting worse dietary and behavioral habits, including those in the high-salt intake subgroup (OR, 2.824; 95% CI, 2.341-3.405) and the 11-20 cigarettes/day subgroup (OR, 2.067; 95% CI, 1.359-3.143). CONCLUSIONS The dietary and behavioral habits of frontline epidemic prevention workers were worse than that those of other participants before COVID-19. They had a greater willingness to adopt healthy dietary and behavioral habits after experiencing the outbreak of COVID-19. However, frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19 continued in engage in these poor habits. Dietary and behavioral intervention policies should be drafted to protect their health, especially frontline epidemic prevention workers with poor habits at baseline.
Adult ; COVID-19/psychology* ; China/epidemiology* ; Cross-Sectional Studies ; Diet/standards* ; Female ; Health Behavior ; Health Knowledge, Attitudes, Practice ; Health Personnel/psychology* ; Humans ; Male ; Risk Reduction Behavior ; SARS-CoV-2 ; Surveys and Questionnaires

Objective To observe the objective response rate, survival and safety of radiotherapy combined with Iressa for patients with locally advanced non-small cell lung cancer ( NSCLC) unsuitable for surgery or concurrent chemoradiotherapy. Methods The patients with locally advanced NSCLC unsuitable for surgery or concurrent chemoradiotherapy were recruited and received thoracic intensity-modulated radiotherapy ( IMRT) combined with Iressa 250 mg daily. Results A total of 30 patients were enrolled between July 2014 and March 2017. Twenty-nine patients were analyzed. At 1 month after radiotherapy,the complete response (CR) was 0,partial response (PR) was 21(72％),stable disease (SD) was 6(21％), progressive disease (PD) was 2(7％),the disease control rate (CR+PR+SD) was 93％,and the objective response rate was 72％. The median follow-up time was 25 months. Fourteen ( 48％) patients died,and 15 (52％) survived. Twenty-three (79％) patients obtained PD including local progression in 18(62％) and distant metastasis in 14(48％). The median survival time (MST) was 26 months and the median PFS was 11 months. The 1-year OS and PFS were 79％ and 44％,and the 2-year OS and PFS were 55％ and 18％. Univariate analysis demonstrated that smoking history and disease stage were influencing factors for OS ( P=0. 035,0. 031) . Moreover, disease stage, the primary tumor diameter, the volume of GTV and PTV were influencing factors for PFS (P=0. 000,0. 016,0. 039,0. 030). Multivariable analysis revealed that disease stage and the volume of PTV were independent prognostic factors for PFS (P=0. 000,0. 012).Two patients ( 7％) developed grade 3 acute adverse events and 7 ( 24％) experienced grade 2 acute irradiation pneumonitis. Conclusions For patients with locally advanced NSCLC unsuitable for surgery or concurrent chemoradiotherapy,IMRT combined with Iressa yields high objective response rate and well tolerance. The long-term clinical efficacy remains to be validated.

Objective To compare the infusion outcome of the posterior interbody autogenous micromor-selized bone graft and structure bone graft ,which were used to cure single-segment spinal tuberculosis. Methods The posterior focus debridement and bone graft fusion were conducted on 35 single-segment spinal tuberculosis patients who were cured by micromorselized bone graft and structure bone graft in the hospital from January 2010 to June 2015. Sixteen patients received micromorselized bone graft cases and 19 patients received structure bone graft. According to JOA and VAS,the fusion effects were compared and analyzed in the following aspects,such as opera-tion time,blood loss volume during the operation,kyphosis distorted Cobb angles before and after the operation and fusion time. Results Follow-up visits were paid to all 35 patients and lasted for 12 to 24 months with an aver-age visit time of 18.5 months. Spinal grafted bones showed desirable fusion without invalid screws and grated bones in the spinal canal.(1)No statistical differences were observed between two groups in terms of post-operation JOA and VAS scores.(2)The operation time and blood loss amount during the operation were smaller in the micromor-selized bone graft than those in the structure bone graft ,with significant differences between 2 groups.(3)No sig-nificant differences were observed between the two groups in terms of kyphosis distortion angle ,but regarding to loss of Cobb angles in different intervals after the operation ,it′s greater in the former group than that in the latter one. (4)No significant differences between the two groups in terms of fusion time were observed. Conclusions The two fusion approaches demonstrated no prominent difference in alleviation of the clinical symptoms and the fu-sion time. The micromorselized bone grafting was superior to the structure bone graft in aspects such as operation time and blood loss amount. However ,it′s more likely for the former to lose Cobb angles in the follow-up visits. Both of the two grafting methods were effective in the single-segment spinal tuberculosis operation. All patients ex-cept those with severely unstable spines and osteoporosis and those were too old can adopt the micromorselized bone grafting approach.

Objective To observe the value of non-invasive positive pressure ventilation for the overlap syndrome complicated with pulmonary encephalopathyt.Methods Fifty-six patients with the overlap syndrome complicated with pulmonary encephalopathy were divided into the experinental group and the controlled group.The experimental group was treated with non-invasive positive pressure ventilation and conventional clinical therapy (drugs and oxygen).The controlled group was treated with conventional clinical therapy.Results The experimental group was better than tche Controlled group in blood gas analysis (PH、PaCO2) in the second hour and the twentyfourth hour after treatment (P ＜ 0.05).The experimental group was more than the controlled group in the improvement of consciousness disorder (P ＜ 0.05).The experimental group was less than the controlled group in tracheal intubation (P ＜ 0.05).Conclusion Non-invasive positive pressure ventilation could improve consciousness disorder of the overlap syndrome complicated with pulmonary encephalopathy,and reduce tracheal intubation.

Objective To investigate the effect of long?term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. Methods To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium?free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non?occupationally cadmium?exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP?MS) was used to test the concentrations of sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann?Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ2 test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. Results The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68)μg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36)μg/g · cr (Z=-10.49, P<0.001). The abnormal rate of urinary cadmium was 51.6%(80/155), which was higher than that of the control group (2.8%(4/143)) (χ2=87.56,P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97)μg/g · cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) μg/g · cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values<0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10 (666.00-1 305.40) μg/g · cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58 (904.53-1 479.18) μg/g · cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively(all P values<0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). Conclusion Long?term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.

Objective To investigate dynamic change of cadmium body burden and renal dysfunction among residents living in cadmium?polluted areas. Methods From April to July of 2011, the cadmium?polluted areas of northern Guangdong province in China was chosen as the study site. Based on the levels of cadmium pollution in soil and rice, the survey areas were divided into low exposed group (average concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil, respectively) and high exposed group (average concentration of cadmium was >0.40 mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and cluster sampling method of epidemiological investigations were carried out among 414 local residents who lived in cadmium exposure areas for more than 15 years, aged above 40, and without occupational cadmium exposure, including 168 and 246 residents in low and high exposed group, respectively. From March to June of 2014, 305 respondents of those who participated in 2011 were successfully traced, including 116 and 189 respondents in low and high exposed group, respectively. We used health questionnaires to acquire their health status. Home?harvested rice and vegetable samples were collected using quartering method for detection of cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190 rice samples, 153 vegetable samples in 2014. Urine specimens of residents were collected for the detection of urinary cadmium and creatinine as well as renal dysfunction biomarkers, namely, N?acetyl?beta?D?glucosamidase (NAG) andβ2?microglobulin (β2?MG), respectively. In 2011 and 2014, Chi?square test was used to investigate the differences of abnormality of cadmium concentration in rice, vegetables and urinary cadmium,β2?MG,and NAG that were expressed as odds ratio (OR) and 95%confidence intervals (95%CI). Results In 2011 and 2014, cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg,and 0.42 (0.20-1.14) mg/kg, respectively (Z=-0.77, P=0.440). In 2011 and 2014, cadmium concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg,and 0.25 (0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and 60.8%(93/153), respectively. In 2014, both average concentration and abnormal rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69,P<0.001 andχ2=15.58, P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in high exposed group were 7.90 (3.96-14.91)μg/g creatinine, 8.64 (4.56-17.60)μg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011, urinary cadmium of high exposed group was significantly increased in 2014 (Z=-2.80 ,P=0.005). In 2011 and 2014, concentrations of β2?MG, NAG P50 (P25-P75) were 0.15 (0.07-0.29)μg/g creatinine, 0.15 (0.07-0.45)μg/g creatinine,and 7.12 (5.05-10.65) U/g creatinine, 13.55 (9.1-19.84) U/g creatinine, respectively, with abnormal rates of 7.5% (23/305), 15.1% (46/305) ,8.2%(25/305) , and 33.8% (103/305), respectively. Compared with baseline in 2011, average concentrations ofβ2?MG, NAG significantly increased in 2014 (Z=-2.263,P=0.024 and Z=-12.52,P<0.001), and abnormal rates ofβ2?MG, NAG were also higher in 2014 (χ2=15.61,P<0.001 andχ2=64.72,P<0.001), with odds ratio (OR) of 2.00 (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). Conclusion Environmental cadmium pollution of crops such as rice and vegetables in survey areas continued to remain high. Body burden of cadmium might kept at sustainably high levels and renal dysfunction was worsened after continuous, long?term cadmium exposure. Our results suggested that NAG might be more sensitive than β2?MG to serve as an indicator for an individual's future tubular function.