1.4‑(Arylethyl)‑pyrrolo2,3-d pyrimidine improves post-traumatic stress disorder in mice by inhibiting mGluR5-regulated ERK1/2-SGK1 signaling pathway.
Cunbao HE ; Shaojie YANG ; Guoqi ZHU
Journal of Southern Medical University 2025;45(4):765-773
OBJECTIVES:
To observe the effect of 4-(arylethynyl)-pyrrolo[2,3-d] pyrimidine (10b) on post-traumatic stress disorder (PTSD)-like behaviors and ERK1/2-SGK1 signaling pathway in mice.
METHODS:
C57BL/6 mouse models exposed to single prolonged stress (SPS) were treated with daily gavage of saline, 10b at low, moderate and high doses, or paroxetine for 14 days. The changes in PTSD-like behaviors of SPS mice with different treatments were observed using behavioral tests. Western blotting and immunofluorescence assay were used to detect the protein expression levels of mGluR5, p-ERK, and SGK1 in the hippocampus of the mice. Pathological changes in the liver and kidney tissues of the mice were examined using HE staining. Molecular docking and molecular dynamics analyses were employed to evaluate the binding stability between the compound 10b and mGluR5.
RESULTS:
Compared to the normal control mice, the SPS mice exhibited obvious PTSD-like behaviors with increased hippocampal expressions of mGluR5 and p-ERK proteins and decreased SGK1 protein expression. Compound 10b significantly ameliorated behavioral abnormalities in SPS mice, inhibited mGluR5 expression, and reversed the dysregulation of p-ERK and SGK1. No obvious liver or kidney toxicity was observed after 10b treatment. Molecular docking and dynamics studies demonstrated a stable interaction between 10b and mGluR5.
CONCLUSIONS
The compound 10b ameliorates PTSD-like behaviors induced by SPS in mice possibly by inhibiting mGluR5 expression to modulate the ERK1/2-SGK1 signaling pathway.
Animals
;
Stress Disorders, Post-Traumatic/drug therapy*
;
Receptor, Metabotropic Glutamate 5/metabolism*
;
Mice, Inbred C57BL
;
Mice
;
Protein Serine-Threonine Kinases/metabolism*
;
Pyrimidines/pharmacology*
;
Immediate-Early Proteins/metabolism*
;
Signal Transduction/drug effects*
;
MAP Kinase Signaling System/drug effects*
;
Male
;
Molecular Docking Simulation
;
Hippocampus/metabolism*
2.Analysis of influencing factors on the protective effect of hearing protectors for noise workers in the petrochemical industry
Jiawei ZHU ; Xi ZHONG ; Shaojie FU ; Qifan HUANG ; Rongzong LI ; Ming LIU ; Shibiao SU ; Hao CHEN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(7):513-517
Objective:To Exploring the protective effect of hearing protectors worn by noise workers in the petrochemical industry and the factors affecting the protective effect of hearing protectors.Methods:From June 2021 to July 2023, 929 petrochemical workers were selected as the research subjects through cluster sampling. The noise exposure of workers and the usage of two types of hearing protectors were surveyed through questionnaire surveys and on-site occupational hygiene surveys. The protective effect of hearing protectors were evaluated by testing the PAR of workers. If the noise exposure value of workers minus the PAR value was less than 85 dB (A) , it was considered passed. Otherwise, it was considered not passed. The passing rate of the protective effect test of hearing protectors was analyzed through chi square test and the influencing factors for the effectiveness of workers hearing protectors in test were explored through single factor analysis and logistic regression models.Results:Among the research subjects, 80.5% of workers (748/929) had noise exposure levels greater than 85 dB (A) . The passing rate (80.9%) of the earmuff is greater than that of the earplug (52.6%) , and the median of PAR of the earmuff is 22 (16, 25) , which is greater than that of the earplug 15 (3, 22) dB dB, with a statistically significant difference ( P<0.001) . Univariate analysis and logistic regression models showed that length of service, exposure level to noise, and wearing comfort were the influencing factors of earplug protection effect ( P<0.05) , while wearing comfort was the influencing factor of earmuff protection effect ( P<0.05) . Conclusion:This study indicates that the protective effect of hearing protectors on workers in the petrochemical enterprise is poor, and the protective effect of earmuffs is greater than that of earplugs. Working experience, noise exposure level, and wearing comfort are the influencing factors of earplug protection effect, while wearing comfort is the influencing factor of earplug protection effect.
3.Analysis of influencing factors on the protective effect of hearing protectors for noise workers in the petrochemical industry
Jiawei ZHU ; Xi ZHONG ; Shaojie FU ; Qifan HUANG ; Rongzong LI ; Ming LIU ; Shibiao SU ; Hao CHEN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(7):513-517
Objective:To Exploring the protective effect of hearing protectors worn by noise workers in the petrochemical industry and the factors affecting the protective effect of hearing protectors.Methods:From June 2021 to July 2023, 929 petrochemical workers were selected as the research subjects through cluster sampling. The noise exposure of workers and the usage of two types of hearing protectors were surveyed through questionnaire surveys and on-site occupational hygiene surveys. The protective effect of hearing protectors were evaluated by testing the PAR of workers. If the noise exposure value of workers minus the PAR value was less than 85 dB (A) , it was considered passed. Otherwise, it was considered not passed. The passing rate of the protective effect test of hearing protectors was analyzed through chi square test and the influencing factors for the effectiveness of workers hearing protectors in test were explored through single factor analysis and logistic regression models.Results:Among the research subjects, 80.5% of workers (748/929) had noise exposure levels greater than 85 dB (A) . The passing rate (80.9%) of the earmuff is greater than that of the earplug (52.6%) , and the median of PAR of the earmuff is 22 (16, 25) , which is greater than that of the earplug 15 (3, 22) dB dB, with a statistically significant difference ( P<0.001) . Univariate analysis and logistic regression models showed that length of service, exposure level to noise, and wearing comfort were the influencing factors of earplug protection effect ( P<0.05) , while wearing comfort was the influencing factor of earmuff protection effect ( P<0.05) . Conclusion:This study indicates that the protective effect of hearing protectors on workers in the petrochemical enterprise is poor, and the protective effect of earmuffs is greater than that of earplugs. Working experience, noise exposure level, and wearing comfort are the influencing factors of earplug protection effect, while wearing comfort is the influencing factor of earplug protection effect.
4.Research progress and thinking on mental health inequality
Shaojie YU ; Juanfang ZHU ; Jinhai SUN ; Lei YUAN
Academic Journal of Naval Medical University 2025;46(7):922-930
Mental health inequality is a major manifestation of health inequality in the psychological dimension,and it has become a realistic problem to challenge common social progress.The aim of this study is to review the domestic and international research on the measurement and decomposition of mental health inequality.The authors mainly discussed 3 aspects:socio-economic and demographic inequalities in mental health,and the impact of acute major infectious diseases on mental health inequality.They also summarized the commonly used indicators and research methods.This paper reviews the selection of data indicators,research subjects,and research perspectives,so as to provide evidence for further research on mental health inequality in China.
5.Efficacy and safety of N-acetylcysteine in treatment of severe alcoholic hepatitis
Fangjiao SONG ; Tianjiao XU ; Yirui YIN ; Hua TIAN ; Sa LYU ; Shaoli YOU ; Shaojie XIN ; Bing ZHU
Journal of Clinical Hepatology 2024;40(12):2484-2491
ObjectiveTo investigate the efficacy and safety of N-acetylcysteine (NAC) in the treatment of severe alcoholic hepatitis (SAH), and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018, and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC (8 g/day, 28 days) was assessed in terms of its safety in SAH patients, its impact on 28-day biochemical parameters, and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure (ACLF-SAH patients) and those without acute-on-chronic liver failure (non-ACLF-SAH patients). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment, suggesting that NAC had a good safety profile. Compared with the control group, NAC did not significantly improve the 28-day biochemical parameters (all P>0.05) and survival rate of SAH patients (P=0.081), but it could improve the 180-day survival rate of SAH patients (67.4% vs 81.0%, χ2=4.280, P=0.039). NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients (both P>0.05); NAC did not improve the 28-day survival rate of non-ACLF-SAH patients (P>0.05), but it could improve the 180-day survival rate of these patients (68.4% vs 88.9%, χ2=4.883, P=0.027). The multivariate Cox regression survival analysis showed that NAC treatment (hazard ratio [HR]=2.530, 95% confidence interval [CI]: 1.334 — 4.796, P=0.004,), Maddrey discriminant function score (HR=3.852, 95%CI: 2.032 — 7.304, P<0.001), and serum sodium level (HR=1.948, 95%CI: 1.079 — 3.517, P=0.027) were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients, and in particular, non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.
6.Analyzing the result of half-mask respirator fit testing in workers exposed to organic solvents and its influencing factors
Qifan HUANG ; Yingyin ZHANG ; Zepeng LI ; Xi ZHONG ; Xi LUO ; Jiawei ZHU ; Shaojie FU ; Shibiao SU
China Occupational Medicine 2024;51(2):183-187
ObjectiveTo analyze the results of fit testing and its influencing factors on half-mask respirator among workers exposed to organic solvents. Methods A total of 84 workers exposed to organic solvents were selected as the research subjects using a convenience sampling method. The qualitative fit test apparatus of respiratory protection was tested after the workers had put on the half-mask respirats, and 11 facial indicators of the subjects were measured. Results The overall pass rate of the respirator fit testing was 71.4% (60/84). The lowest pass rate was 63.1% (53/84), which occurred during bending movements of workers. The head width, minimum forehead width, face length, nose length, nose depth, head circumference and head length were higher in workers who passed respirator fit testing, compared with those in the failing group (all P<0.05). The result of binary logistic regression analysis showed that gender and face width were influencing factors of the respirator fit testing (both P<0.05). Female workers had a lower pass rate of the fit testing than male workers, and workers with larger face width had a lower pass rate in the fit testing. Conclusion Drastic movement may lead to a decrease in the seal of half-mask respirator of workers exposed to organic solvents. When providing half-mask respirator to workers exposed to organic solvents, employers need to pay attention to the fit of respirators of female works and those with larger face width to ensure the effectiveness of respiratory protection for workers.
7.Clinical, imaging and pathological and molecular characteristics of simple bone cyst
Xuxi YANG ; Shaojie SHENG ; Yuefen ZOU ; Yan ZHU ; Ying DING ; Qinhe FAN ; Qixing GONG
Chinese Journal of Pathology 2024;53(3):243-249
Objective:To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses.Methods:Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis.Results:There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur ( n=4), humerus ( n=5) and iliac bone ( n=5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions:EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.
8.Analysis on incidence, mortality and disease burden of acute myocardial infarction in Qingdao, 2014-2020
Xiaohui SUN ; Haiping DUAN ; Canqing YU ; Wenzhong ZHANG ; Jing ZHANG ; Xuefen YANG ; Hua ZHANG ; Xiaojia XUE ; Yuanyuan ZHAO ; Zengzhi ZHANG ; Jintai ZHANG ; Conglin MAO ; Zhigang ZHU ; Kang WANG ; Haiyan MA ; Xiaoyan ZHENG ; Hongxuan YAN ; Shaojie WANG ; Feng NING
Chinese Journal of Epidemiology 2023;44(2):250-256
Objective:To describe the characteristics and change trends of incidence, mortality and disease burden of acute myocardial infarction (AMI) in Qingdao from 2014 to 2020.Methods:We analyzed the incidence data of AMI retrieved from Qingdao Chronic Diseases Surveillance System. The average annual percent change (AAPC) of morbidity and mortality of AMI were evaluated by using Joinpoint log-linear regression model. Disability adjusted life year (DALY) was used to estimate disease burden of AMI in Qingdao.Results:A total of 70 491 AMI cases and 50 832 deaths of AMI occurred in Qingdao from 2014 to 2020. The age-standardized morbidity and mortality were 54.71/100 000 and 36.55/100 000, respectively. During 2014-2020, the AAPC of age-standardized morbidity was 2.86% (95% CI: 0.42%-5.35%), and 4.30% (95% CI: 1.24%-7.45%) in men and 0.78% (95% CI: -0.89%-2.47%) in women, respectively. The log-linear regression model showed that age-standardized morbidity in age groups 30-39, 40-49 years increased rapidly, with the AAPCs of 8.92% (95% CI: 2.23%-16.06%) and 6.32% (95% CI: 3.30%-9.44%), respectively. The trend was also observed in age groups 30-39, 40-49 and 50-59 years in men, with the AAPCs of 11.25% (95% CI: 3.54%-19.54%), 6.73% (95% CI: 2.63%-10.99%) and 6.72% (95% CI: 2.98%-10.60%), respectively. There was no significant change in age-standardized mortality. The DALY rate increased from 7.49/1 000 in 2014 to 8.61/1 000 in 2020, with the AAPC of 1.97% (95% CI: 0.36%-3.60%). Conclusions:The age-standardized morbidity of AMI in men increased in Qingdao, especially in those aged 30-49 years, while age-standardized mortality rate of AMI was relatively stable from 2014 to 2020. The burden of disease of AMI increased in both men and women.
9.The clinical value of coronary artery calcification in early screening of coronary atherosclerotic heart disease in civil pilots
Lin ZHANG ; Qingqing JIN ; Qingqing DUAN ; Yan XU ; Qiuyu SHEN ; Shaojie ZHU ; Kai CHEN ; Jie GAO ; Yukai LI ; Yan CHEN ; Xuejun ZHAO ; Meng SONG ; Jinke ZHENG ; Bin REN
Chinese Journal of Aerospace Medicine 2023;34(4):210-214
Objective:To explore the clinical value of coronary artery calcification (CAC) detected by chest CT in early screening of coronary atherosclerotic heart disease (CAHD) in civil pilots.Methods:The physical examination data of 2 899 civil pilots were retrospectively analyzed. Pilots were divided into CAHD group and control group based on the results of coronary angiography (CAG). The health data were compared between 2 groups and the clinical value of CAC in the diagnosis of CAHD was analyzed by using binary Logistic regression model and receiver operating characteristic (ROC) curve.Results:Thirty-eight CAHD cases were diagnosed, and the remaining 2 861 were in the control group. Comparing to that of control group, the average age of the pilots in CAHD group was greater ( t=12.09, P<0.001), and the average total flying hours were longer ( Z=-7.68, P<0.001). The proportions of smoking, hyperlipidemia, diabetes, hypertension, fatty liver, obesity, carotid plaques, positive or suspiciously positive in submaximal treadmill exercise test, CAC, as well as the proportions of taking further requested coronary CT angiography and CAG were significantly higher in the CAHD group ( χ2=5.42-1 430.25, P<0.01 or <0.05). Logistic regression model showed that smoking ( OR=2.800, 95% CI: 1.074-7.301, P=0.035), obesity ( OR=3.336,95% CI:1.243-8.956, P=0.017), positive or suspiciously positive in submaximal treadmill exercise test ( OR=17.669, 95% CI: 2.923-106.756, P=0.002) and CAC ( OR=96.039, 95% CI: 11.439-806.396, P<0.001) were the independent risk factors for diagnosing CAHD. The ROC curve results suggested that the sensitivity and specificity of CAC for predicting CAHD was 97.4% and 93.1%, respectively, and the area under the ROC curve was 0.952 ( P<0.001). Conclusions:CAC detected by chest CT in physical examination is helpful for early screening of asymptomatic or atypical CAHD in civil pilots.
10.Development of hypothermia after spinal anesthesia and risk factors
Jing ZHANG ; Shaojie ZONG ; Xinyan ZHU ; Xueyao YU ; Zhengqian LI ; Yi LIU ; Jiechu WANG
Chinese Journal of Anesthesiology 2023;43(2):152-155
Objective:To evaluate the development of hypothermia after spinal anesthesia and risk factors.Methods:Patients undergoing spinal anesthesia in the anesthesia preparation room of our hospital from April 2020 to April 2021 were included. The temperature of the tympanic membrane was measured before spinal anesthesia and immediately after anesthesia and at 5, 10 and 15 min after anesthesia. Patients with tympanic membrane temperature<36 ℃ at any time point were considered as having hypothermia and included in hypothermia group and patients with membrane temperature ≥ 36 ℃ were considered as having no hypothermia and included in non-hypothermia group. The patients′ demographic data, highest anesthesia plane, puncture space of spinal anesthesia, types of anesthetics, preoperative fasting time, and surgical sites were recorded. The multivariate logistic regression analysis was performed to identify the risk factors for hypothermia.Results:A total of 196 patients were finally enrolled. The body temperature was significantly decreased at 5 and 10 min after anesthesia compared with the baseline body temperature before anesthesia and immediately after anesthesia ( P<0.001), and the incidence of hypothermia was 10.2%. The multivariate logistic regression analysis showed that female and high anesthesia plane were independent risk factors for hypothermia, and higher baseline body temperature was an independent protective factor for hypothermia ( P<0.05). Conclusions:Body temperature decreases at 5-10 min after spinal anesthesia, and the occurrence of hypothermia is not a small probability event in the patients undergoing spinal anesthesia; female and higher anesthesia plane are risk factors and higher baseline body temperature is the protective factor.

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