1.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
2.Analysis on comprehensive noise control effects in an automobile engine manufacturing enterprise
Lin CHEN ; Youmei SHU ; Yang LIAO ; Hai ZHANG ; Kunpeng ZHONG ; Jun LIU ; Fengyi OU ; Zhi WANG
China Occupational Medicine 2024;51(2):168-171
ObjectiveTo analyze the measures and effects of comprehensive noise control in an automobile engine manufacturing enterprise. Methods An automobile engine manufacturing enterprise with noise exposure work-sites was selected as the research subject. The noise hazard status of the enterprise was investigated. The noise hazard exceeded the national standard in work-sites was comprehensively treated. The treatment effect was analyzed. Results A total of 395 work-sites exposed to noise were detected. Among them, 16 work-sites exceeded the national noise standard, with the rate of 4.1%. The work-sites with noise exceeding the national standard were mainly in the machine workshop and the casting workshop, with normalization of equivalent continuous A-weighted sound pressure level to a nominal eight hours working day (LEX,8h) ranging from 86.8 to 89.2 and 85.2 to 90.2 dB(A), respectively. In addition, the classification of occupational noise exposure of the mold protection group in the casting workshop was level Ⅱ, and classification of occupational noise exposure of other work-sites with excessive national standard was grade Ⅰ. After the enterprise implemented noise control measures such as process reform, equipment replacement, sound insulation, noise reduction, sound absorption, and vibration isolation, the LEX,8h of nine positions were lower than those before rectification [(86.7±1.1) vs (83.3±1.3) dB(A), P<0.01]. Conclusion The use of comprehensive control measures can achieve the purpose of reducing noise from the sources, and can be used for reference by relevant enterprises with noise hazards.
3.Quality evaluation on diagnostic accuracy research in China from 2017 to 2022 based on STARD2015
Jing ZHANG ; Wenxu YANG ; Youmei LU ; Xuyao JI ; Yu LIU
Chinese Journal of Laboratory Medicine 2024;47(3):308-313
Objective:The quality of domestic diagnostic accuracy research was evaluated to explore the quality level of domestic diagnostic accuracy research based on Standards for Reporting of Diagnostic Accuracy 2015 (STARD2015).Methods:The Chinese core journals of CNKI and Wanfang Database were searched, and research literature on diagnostic accuracy published from 2017 to 2022 were collected. The main search terms are diagnostic test, sensitivity, specificity, receiver operating characteristic (ROC) curve, etc. The literature was selected according to the inclusion criteria, and the quality of the included literature was evaluated independently by two reviewers, and the conformity rate of the STARD2015 report and the STARD2015 article was calculated. The report quality of the literature was divided into three levels (low, medium and high) according to the conformity rate of the STARD2015 report. The proportion of literature at each level and the proportion of literature at medium and high level in each year were counted. According to quality analysis on the contents of the included articles, articles were divided into standardized reports and unstandardized reports. Intragroup correlation coefficient ( ICC) was used to analyze the consistency of two reviewers. The trend Chi-square test was used to analyze the trend of the proportion of medium and high level literature in each year. One-way analysis of variance was used to compare the coincidence rates evaluated by STARD2015 for each year. Results:A total of 6 771 studies on diagnostic accuracy published from 2017 to 2022 were included. The compliance rate sccording to STARD2015 was 39.56%±4.90%, and the reported compliance rate ranged from 17.65% to 64.71% (the number of reported items ranged from 6 to 22), and 93.53% (6 333/6 771) literatures were in the middle level. Compliance rate of STARD2015 reports varied significantly among different years ( F=25.023, P<0.01), and the compliance rate of 2021 was significantly higher than that of other years ( P<0.01). The proportion of medium and high level literatures according to STARD2015 showed an increasing trend ( χ 2=14.099, P<0.01). The reporting situation of each item varied significantly, and the conformity rate of items raned from 0 to 100%. According to report item, non-standard report rate was 10.34% (569/5 503) for item 6, 4.15% (277/6 677) for item 8, 21.84% (1 447/6 626) for item 20, 66.67% (24/36) for item 22, and 26.03% (877/3 369) for item 26. Conclusions:The overall report quality of published domestic literature on diagnostic accuracy from 2017 to 2022 is at a medium level according to STARD2015, and the reports conformity rate of each item vary significantly, indicating significant knowledge gap on STARD2015 among domestic researchers. The promotion of STARD2015 needs to be strengthened.
4.The underlying mechanism of autophagy regulating liver injury with obstructive jaundice in Sprague-Dawley rats
Jianwen YE ; Wenhui CHEN ; Youmei PENG ; Lei QI ; Hongwei TANG ; Wentao LIU ; Yitao WANG
Chinese Journal of Hepatobiliary Surgery 2022;28(2):127-132
Objective:To investigate the effect of autophagy on liver injury with obstructive jaundice in Sprague-Dawley (SD) rats and its underlying mechanism.Methods:Thirty-five healthy male SD rats, SPF grade, aged 6-8 weeks, weighting 200-300 g, were divided into 5 groups with 7 rats in each group, including sham group (simple free common bile duct, without ligation, intraperitoneal injection of normal saline), obstructive jaundice (OJ) group (established by common bile duct ligation, intraperitoneal injection of normal saline), OJ group with 3-MA, OJ group with Rapamycin, and OJ group with 3-MA and VX-765. Morphological changes in liver tissues were analyzed with HE staining. Expression of autophagy-related protein Atg5 was detected by immunohistochemistry staining. Liver function was analyzed by automatic biochemical instrument and the level of serum interleukin (IL)-18 was detected using ELISA assay. Protein levels of autophagy related-proteins and endoplasmic reticulum stressed (ERs)-related apoptosis proteins were detected by Western Blot.Results:The relative expression of autophagy related protein Atg5 in OJ group was significantly higher than that in sham group [(5.0±1.0) vs. (2.8±1.3), t=-3.00, P<0.05]. Compared with sham group, the activity of autophagy was enhanced and the protein levels of Caspase-1/p-65 and IL-18 were significantly increased in OJ group. At the same time, apoptosis was induced by activating ERs. In OJ group, the autophagy inducer 3-MA improved the expression levels of Caspase-1/p-65 and IL-18, and aggravate liver injury. While after applying the autophagy agonist Rapamycin in OJ rat models, the expression of Caspase-1/p-65 and IL-18 was repressed and liver damage was also reduced. In addition, in rat OJ groups with 3-MA, inhibition of Caspase-1 by VX-765 could down regulate the expression of Caspase-1/p-65 and IL-18, and protect against liver injury. Conclusions:Both ERs related apoptosis and autophagy were activated after ligation of common bile duct. Besides, activation of autophagy could reduce OJ-induced liver injury in SD rats by inhibiting the Caspase-1/p-65 inflammatory pathway.
5. Application of three methods in occupational health risk assessment of automobile 4S shop
Lin CHEN ; Zibo CEN ; Weiyu MA ; Yali JIN ; Youmei SHU ; Yimin LIU ; Xudong LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(11):866-870
Objective:
To choose various occupational health risk assessment of the mature methods at home and abroad respectively occupational health risk assessment was carried out on the 4s stores, to explore different risk assessment methods on the 4 s shop the applicability of the occupational health risk assessment.
Methods:
Chemical was applied on the harmful factors of occupational health risk assessment technology guideline in the composite index method, quantitative cancer risk assessment method using the guidelines for the harmful factors of occupational health risk assessment of chemical technology of composite index method, quantitative cancer risk assessment method, international commission on mining and metals (ICMM) occupational health risk assessment quantitative method and the occupational-disease-inductive operation classification to evaluate chemical factors in 4S store, Combined with on-site occupational health investigation to compare with the result of risk assessment and analysis of international mining and metals (ICMM) committee occupational health risk assessment quantitative method and the occupational-disease-inductive operation classification of 4S store to evaluate chemical factors, combined with on-site occupational health investigation comparison and analysis the result of the risk assessment.
Results:
Except for 6 times, the results of ICMM matrix method and comprehensive index method were consistent, which were all higher than job classification. The other results were job classification of >of ICMM matrix method >comprehensive index method or job classification of >of ICMM matrix method.
Conclusion
When the concentration of occupational-disease-inductive factors is lower than 1/2 limit, the risk assessment results tend to be ICMM quantitative >composite index method >operation classification. When the occupational-disease-inductive factors were involved with triphenyl, the quantitative non-carcinogenic risk assessment method was more likely to reach the conclusion that the occupational health risk was unacceptable.
6.Failure patterns of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma: implications for the target area design of postoperative therapy
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU
Chinese Journal of Radiological Medicine and Protection 2018;38(4):265-272
Objective To analyze the failure patterns and prognostic factors of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma (TESCC),and the implications for the target area design of postoperative therapy.Methods We retrospectively analyzed 1 191 patients with TESCC who underwent radical surgery at our institution.The failure patterns,the prognostic factors,as well as the effects of lesion locations and N stage on the failure patterns were analyzed.Results The thoracic-region recurrence rate and the distant metastasis rate was 31.7% and 16.4% in all patients.The multivariate analysis showed that the lesion locations,the degree of inflammatory adhesion,T staging,N staging and the rate of lymph nodes metastasis were independent factors affecting the regional recurrence (P < 0.05).Gender,tumor differentiation and the rate of lymph nodes metastasis were independent factors affecting distant metastasis (P < 0.05).The intrathoracic lymph nodes recurrence rate of upper/middle TESCC was significantly higher than that of the lower TESCC (x2 =6.179,P =0.046),while the abdomen lymph nodes recurrence rate of the lower was significantly higher than that of upper/middle TESCC (x2 =15.853,P < 0.05).The recurrence rate and distant metastasis rate of stage N1 patients were significantly higher than that of N0 patients (x2 =7.764-56.495,P < 0.05).The abdomen lymph nodes recurrence rate of stage N1 patients was significantly higher than that of N0 in upper TESCC (x2 =7.905,P <0.05).The supraclavicular and intrathoracic lymph nodes recurrence rates of stage N1 patients were significantly higher than that of N0 patients in middle TESCC (x2 =12.506,18.436,P < 0.05).The supraclavicular lymph nodes,anastomosis and abdomen lymph node recurrence rates of stage N1 were significantly higher than that of N0 patients in lower TESCC (x5 =5.272,4.878,18.006,P < 0.05).The anastomotic recurrence rate of stage T3+4 was higher than that of T1+2 in middle/lower TESCC (x2 =4.341,7.154,P < 0.05),and the abdominal lymph nodes recurrence rate of stage T3 +4 was higher than that of T1 +2 in lower TESCC (x2 =5.366,P < 0.05).Conclusions The lymphatic drainage regions for postoperative radiotherapy (PORT) are selective.We suggest that abdominal lymph nodes drainage area should be noted for the stage N1 patients with upper TESCC,and the supraclavicular lymph nodes drainage area should be noted for the N1 patients with lower TESCC.In addition,the anastomosis is suggested to be included in PORT target area for stage T3/T4 middle/lower TESCC patients.
7.Efficacy of postoperative chemoradiotherapy after radical resection of squamous cell carcinoma of upper thoracic esophagus
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU ; Jinrui XU
Chinese Journal of Radiological Medicine and Protection 2018;38(5):355-359
Objective To compare the prognosis of patients with squamous cell carcinona of the upper thoracic esophagus after radical resection with and without postoperative chemoradiotherapy (POCRT).Methods From January 2007 to December 2011,168 patients with upper thoracic esophageal carcinoma who were treated in the Fourth Hospital of Hebei Medical University were retrospectively included in this study.According to the different treatment method,they were divided into simple surgery group (86 cases) and POCRT group (82 cases) respectively.Based on SPSS statistical software,the group data composition,prognostic analysis and multivariate prognostic analysis were performed by x2 test,Log-rank method and Cox regression model,respectively.Results The 1,3,5 year-survival rate,recurrence rate and distant metastasis rate were 83.9%,52.4%,43.5%,26.5%,40.8%,43.4% and 5.3%,11.4%,16.9%,respectively.The result of multivariate analysis showed that gender,T stage,N stage and treatment method were independent prognostic factors of overall survival (P =0.020,0.008,0.005,0.000);N staging and treatment method were the independent prognostic factors of local/regional recurrence (P =0.001,0.003);differentiation and T staging were the independent prognostic factors of distant metastasis (P =0.045,0.020).The intrathoracic regional recurrence rate of operation only group and POCRT group patients were 44.2% (38/86) and 29.3% (24/82) respectively,where the difference was statistically significant (x2 =7.110,P < 0.05).The rate of metastasis were 19.8% (17/86) and 13.4% (11/82) respectively without significant difference (P >0.05).Conclusions The recurrence rate of patients with upper thoracic esophageal squamous cell carcinoma after radical resection was still high.Postoperative chemoradiotherapy can improve the overall survival rate and reduce the recurrence rate,but whether it can reduce the patient's distant metastasis rate needs further study.
8.Abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma:risk factors and guidance for postoperative radiotherapy
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU ; Jinrui XU
Chinese Journal of Radiation Oncology 2018;27(2):135-139
Objective To analyze the risk factors for abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma (TE-SCC),and to design the target volume for postoperative radiotherapy based on the results.Methods A retrospective study was performed among 913 patients with middle TE-SCC undergoing radical surgery who were admitted to our hospital from 2007 to 2012.Influencing factors were analyzed for abdominal lymph node recurrence after treatment.The efficacy was compared between different treatment methods in the high-risk population.Comparison of categorical data was made by chi-square test.The overall survival rates (OS) were calculated by the Kaplan-Meier method and analyzed by the univariate log-rank analysis.The influencing factors for abdominal lymph node recurrence were analyzed by the multivariate logistic regression equation.Results After treatment,37 patients had abdominal lymph node recurrence,yielding a recurrence rate of 4.1%.A total of 53 recurrent sites were found.The univariate analysis showed that no/low differentiation,pT3+4 stage,no less than 3 positive postoperative lymph nodes,and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P =0.032,0.001,0.009,0.000).The multivariate regression analysis showed that pathological T staging and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P=0.011,0.000).For patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes,postoperative radiotherapy improved OS and local control rates but failed to reduce the distant metastasis-free rate.Conclusions T staging and positive postoperative abdominal lymph nodes are important risk factors for abdominal lymph node recurrence after radical surgery in patients with middle TE-SCC.Postoperative adjuvant therapy is recommended for patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes.
9.Comparison of different treatment modalities in node-positive patients after radical resection for squamous cell carcinoma of the thoracic esophagus
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU ; Jinrui XU
Chinese Journal of Radiation Oncology 2018;27(3):250-255
Objective To compare the efficacy between different modalities in the treatment of positive lymph nodes after radical resection for squamous cell carcinoma of thoracic esophagus(TESCC),and to explore the best treatment mode. The Kaplan?Meier method was used to calculate survival rates. The log-rank test and Cox model were used for univariate and multivariate prognostic analyses,respectively. Methods A retrospective analysis was performed among 548 patients with TESCC who were admitted to our hospital and had positive lymph nodes after radical resection. The efficacy of different treatment methods was evaluated. Propensity scores(PSM)were used to make 1-to-1 patient matching between different treatment groups to further analyze and figure out the best treatment model for patients. The Kaplan?Meier method was used to calculate the overall survival(OS)and disease-free survival(DFS)rates. The log-rank test was used for survival analysis and univariate prognostic analysis. The Cox regression model was used for multivariate prognostic analysis. Results In all patients,the 1-,3-,and 5-year OS rates were 79.9%, 38.1% and 28.5%,respectively,while the 1-,3-,and 5-year DFS rates were 68.5%,39.8% and 32.5%, respectively. After 1-to-1 matching based on PSM,there were no differences in general clinical pathological data between the four groups. After PSM,there were significant differences in 1-,3-,and 5-year OS and DFS rates between the surgery alone group,the postoperative radiotherapy group,the postoperative chemotherapy group,and the postoperative chemoradiotherapy(POCRT)group(P=0.000,0.000).There were significant differences in OS and DFS rates between patients with stage N1,N2,and N3disease(P=0.000,0.000).The result of the Cox multivariate analysis showed that treatment method and N staging were two independent prognostic factors for OS and DFS(P=0.001,0.000,0.025,0.016). Conclusions Patients with positive lymph nodes after radical resection for TESCC have a poor prognosis. Moreover,the prognosis becomes worse with the increase in metastatic lymph nodes. POCRT may improve the survival in those patients. Prospective studies are needed to further confirm those conclusions.
10. Clinical observation of orthokeratology lens in the treatment of mild and moderate myopia
Lijun JIANG ; Yongwei ZHU ; Youmei ZHANG ; Yamin HU ; Lingling LIU
Chinese Journal of Primary Medicine and Pharmacy 2018;25(17):2236-2239
Objective:
To observe the clinical effects and safety of orthokeratology(OK) lens in the treatment of mild and moderate myopia, and to evaluate the effects on the myopia control.
Methods:
The study included a total of 166 eyes in 83 myopia children who were treated in Jiaxing Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University from January 2014 to December 2014.They were randomly divided into two groups according to the digital table, 43 cases(86 eyes) in the observation group underwent standard OK lens, and the other 40 cases(80 eyes) in the control group were given common spectacles.The patients were followed up for two years.The uncorrected visual acuity, corneal curvature and ocular surface in the, observation group were examined, and diopter, axial length were examined in the two groups.
Results:
The visual acuity of the observation group improved significantly at 1 day, trended to be stable at 1 week, and then was basically stable within 1 year, but decreased at 2 years.After 3 months, the mean corneal curvature[(41.93±1.12)D]was significantly lower than before orthokeratology[(43.56±1.44)D], and the difference was statistically significant(

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