Background Hypertension is one of the chronic diseases with the highest prevalence in China, and a history of hypertension may potentially exacerbate hearing loss. Investigating the association between long-term blood pressure trends and hearing thresholds could contribute to hearing protection efforts for occupationally noise-exposed populations. Objective By investigating hearing thresholds and blood pressure levels among occupationally noise-exposed workers in an urban rail transit enterprise, and conducting a comprehensive analysis of the association between long-term blood pressure changes and hearing thresholds, to provide data references for health management strategies targeting occupationally noise-exposed workers. Methods Workers exposed to occupational noise at a rail transit enterprise were enrolled as study subjects and underwent pure-tone audiometry. Group-based trajectory modeling was employed to identify blood pressure trajectories. Categorical data were compared using chi-square tests, while normally distributed continuous variables were analyzed via t-tests and analysis of variance (ANOVA). Generalized linear mixed models (GLMMs) were subsequently applied toexamine associations between these trajectory groups and high-frequency hearing thresholds. Results Among 2 002 occupationally noise-exposed workers, the median (P₂₅, P₇₅) age was 32 (28, 35) years, with a median (P₂₅, P₇₅) working tenure of 7 (3, 10) years. In 2019, the positive hypertension rate was 9.04%, with a mean systolic blood pressure (SBP) of (122.97±11.60) mmHg and a mean diastolic blood pressure (DBP) of (76.37±9.02) mmHg. The hearing loss prevalence was 10.1%, showing bilateral high-frequency average hearing thresholds of (17.18±8.71) dB and speech-frequency average thresholds of (13.79±3.46) dB. Three distinct trajectory groups were identified for both SBP and DBP. Compared with other trajectory groups, the high-stable DBP group exhibited significantly higher hearing loss prevalence (χ²=6.34, P=0.042) and elevated high-frequency hearing thresholds (all Ps<0.05). Specifically, within the 30-39 age subgroup, the moderate-stable DBP group demonstrated 1.96 dB lower high-frequency thresholds than the high-stable group [β(95%CI): −1.96 (−3.61, −0.32), P=0.020]. Conclusion Among occupationally noise-exposed workers in a municipal rail transit enterprise, DBP trajectories demonstrated a positive association with high-frequency hearing thresholds. Notably, in young and middle-aged occupationally noise-exposed populations, DBP may exert a more critical influence than SBP on the progression of hearing loss.

Objective To investigate the characteristics of ST segment changes in middle-aged and elderly people in Fuzhou through cardiopulmonary exercise test and to analyze its possible influencing factors, in order to provide theoretical guidance for cardiovascular prevention. Methods A total of 987 individuals undergoing health examination at the physical examination center of 900TH Hospital of Joint Logistics Support Force from 2017 to 2023 were collected as study subjects, and cardiopulmonary exercise tests were performed, and the exercise maximum heart rate (/min), resting systolic blood pressure (mm Hg), resting diastolic blood pressure (mm Hg), peak systolic blood pressure (mm Hg),，carbon dioxide ventilation equivalent (%) ，Borg score (score) and other index data were collected, using Logistic regression to analyze the influencing factors of ST segment anomalies. Results A total of 234 ST-segment abnormalities occurred, and the abnormal rate was 23.72%. Among them, 148 cases (14.99%) were depressed in ST segment, 52 cases (5.27%) were elevated in ST segment, 13 cases (1.32%)was extended in ST segment , and 21 cases (2.14%) was shortened in ST segment . The ST-segment abnormal group had higher exercise maximum heart rate (/min), resting systolic blood pressure (mm Hg), resting diastolic blood pressure (mm Hg), peak systolic blood pressure (mm Hg), peak diastolic blood pressure (mm Hg), carbon dioxide ventilation equivalent (%) and Borg score (score) than the normal group, and the differences were statistically significant. The results of multivariate regression analysis showed that peak systolic blood pressure (mm Hg), carbon dioxide ventilation equivalent (%) and Borg score (score) were the influencing factors in the ST segment depression ; the peak systolic blood pressure (mm Hg) and Borg score (score) were the influencing factors in the ST segment elevation(OR>1). Conclusion Peak systolic blood pressure (mm Hg), carbon dioxide ventilation equivalent (%) and Borg score (score) are the influencing factors of ST segment abnormalities in cardiopulmonary exercise test in middle-aged and elderly people , and their measurement is of great significance for cardiovascular health evaluation and treatment.

OBJECTIVE To study the effect of 60Co-γ irradiation on the sterilization effect and main components of Rubus chingii Hu. METHODS Irradiated Rubus chingii Hu by 0, 6, 10, 15, 30 kGy doses of 60Co-γ, used the microbial count method to determine the microbial level of Rubus chingii Hu before and after irradiation. Analyzed the components of Rubus chingii Hu by high resolution mass spectrometry, investigated the effects of irradiation on the quality of Rubus chingii Hu by comparing the components of Rubus chingii Hu samples before and after irradiation, analyzing the quantitative results of ellagic acid and kaempferol 3-O-yunxiangoside, and evaluating the similarity of fingerprints. RESULTS The results of microbial examination of Rubus chingii Hu after different doses of irradiation all met the requirements, cluster analysis and principal component analysis of 20 components showed no significant difference. And there was no significant difference in the contents of ellagic acid and kaempferol 3-O-glucoside before and after irradiation. The similarity of fingerprints before and after irradiation was between 0.995 and 1.000. CONCLUSION Irradiation can effectively control the microbial level in Rubus chingii Hu, and there is no significant effect on the chemical composition of Rubus chingii Hu, the results provide a basis for the application of irradiation in the sterilization process of Rubus chingii Hu.

OBJECTIVE To investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.

OBJECTIVE To establish a ultra-high-performance liquid chromatography-mass spectrum/mass spectrum(UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. METHODS Zanubrutinib was used as internal standard and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18(100 mm×2.1 mm, 3.0 μm) column using acetonitrile and 10 mmol·L−1 ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL·min−1 and injection volume was 5 μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at m/z 408.1→339.1 for anlotinib and m/z 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. RESULTS The method was validated over the concentration range of 1.0−100.0 ng·mL−1, with R2=0.998 4. The precision RSD was<9%, the recovery and matrix effect were 104.81%−107.32% and 102.54%−105.26%, respectively, and this method had good stability and was not affected by matrix effect. The method had been used for determined 52 advanced non-small cell lung cancer patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than lower limit of quantitation (1.0 ng·mL−1) from 52 patients. The plasma concentration of anlotinib Ctrough was (11.38±4.29)ng·mL−1 with 37.66% coefficients of variation, which were shown large inter-patient variability. CONCLUSION This method is high sensitivity, specificity and accurate, and suitable for determination of anlotinib in human plasma.

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.