OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

Psychological factors have become significant contributors to the onset and progression of insomnia. This article explored the treatment of insomnia from the perspective of “liver governs wei qi （defensive qi）”. The concept of “liver governs wei qi （defensive qi）” is summarized in three aspects， firstly， the liver assists the spleen and stomach in transformation and transportation， governing the generation of wei qi； secondly， the liver aids lung qi diffusion and dispersion， governing the distribution of wei qi； thirdly， the liver regulates circadian rhythms， governing the circulation of wei qi. It is proposed that the clinical treatment of insomnia should focus on the following methods： for regulating the liver to harmonize the five viscera， and facilitate the circulation of wei qi， medicinals entering the liver channel include Chaihu （Bupleuri radix）， Baishao （Paeoniae Radix Alba）， Zhizi （Gardeniae Fructus）， and Suanzaoren （Ziziphi Spinosae Semen） could be commonly used； for nourishing the liver， the treatment should align with the day-night rhythm， and herbs such as Baihe （Lilium）， Hehuan （Albizia julibrissin）， and Yejiaoteng （Polygoni multiflori caulis） are commonly used； for soothing the liver and address both mental and physical health to calm wei qi， treatment should advocate verbal counseling， psychological regulation， and health education. Ultimately， this treatment approach can free liver qi to flow， soothe qi movement， restore the motion of wei qi， regulate during day and night， balance yin and yang， and resolve insomnia effectively.

OBJECTIVE To analyze the cost-effectiveness of abemaciclib， palbociclib and ribociclib combined with aromatase inhibitors （AI） in first-line treatment of hormone receptor-positive （HR+） advanced breast cancer from the perspective of Chinese medical system. METHODS The 20-year disease course of the patients was simulated by the partitioned survival model， and the simulation period was determined to be 4 weeks， the model output was the total cost and quality-adjusted life year （QALY）， the cost and effect were discounted at a discount rate of 5%. A network meta-analysis was constructed by systematically searching relevant clinical trials to obtain the efficacy parameters of abemaciclib， palbociclib and ribociclib combined with AI. Survival fitting and extrapolation were performed based on the survival curve of the placebo group in MONALEESA-2 trial. Cost-effectiveness was assessed by incremental cost-effectiveness ratio （ICER） and incremental net monetary benefit （INMB）， with a willingness-to-pay threshold of 3 times China’s per capita gross domestic product （GDP） in 2023； one-way sensitivity analysis and probability sensitivity analysis were used to detect the influence of parameters on the results and the robustness of the incremental analysis results. RESULTS In the 20-year simulation， compared with palbociclib+AI scheme， the ICER of ribociclib+AI scheme was 58 558.38 yuan/QALY and the INMB was 62 988.20 yuan. Compared with ribociclib+AI scheme， the ICER of abemaciclib+AI scheme was 264 928.34 yuan/QALY and the INMB was 344.84 yuan. One-way sensitivity analysis showed that the incremental analysis results of abemaciclib+AI scheme compared to ribociclib+AI scheme were not robust. Probabilistic sensitivity analysis confirmed that the probability of ribociclib+AI scheme becoming the most economical was the highest when the threshold was 1-3 times China’s per capita GDP in 2023. CONCLUSIONS Ribociclib+AI scheme is more likely to be the most economical first-line treatment than abemaciclib+AI scheme and palbociclib+AI scheme in Chinese patients with HR+ advanced breast cancer when threshold is 1-3 times China’s per capita GDP in 2023.

BACKGROUND:Prosthesis loosening and wear are still the main problems in the failure of total ankle replacement,which are closely related to the micro-motion of the implant-bone interface,the contact stress of the articular surface and joint motion.The design of artificial joint components,including insert and tibial/talar stem prosthesis,is a key factor affecting the force,motion,and micromotion of the contact interface of the ankle joint.The development of new inserts is of great significance to improve the survival rate of artificial ankle joints. OBJECTIVE:The finite element model of the total ankle replacement model was constructed to detect the biomechanical properties of the porous structure-optimized inserts,and the effect of the porous structure-optimized inserts on reducing prosthesis micromotion and improving the contact behavior of the articular surface was analyzed. METHODS:Based on the CT scan data of the right ankle joint of a healthy adult and the INBONE Ⅱ system product manual,a three-dimensional model including bone and artificial joint system was established,and the total ankle replacement model(model A)was obtained after osteotomy and prosthesis installation,and then through four new types of inserts,G50,G60,D50,and D60,were obtained by transforming the porous structure of the original insert,and the original one was replaced with different inserts to establish an optimized total ankle replacement model(models B-E)corresponding to the inserts.The gait loads were applied on the five models to simulate the gait conditions.The differences in micromotion and articular surface contact behaviors at the implant-bone interface of all five models were compared. RESULTS AND CONCLUSION:(1)In the gait cycle,the micromotion of the prosthesis of the four optimized total ankle replacement models was lower than that of the original model.Compared with model A,the micromotion of the prosthesis in models B-E decreased by 5.4%,10.1%,8.1%,and 20.9%,respectively.The high micromotion area of t ??he tibial groove dome in the optimized model was significantly smaller than that of the original model.(2)The four optimized models obtained a larger articular surface contact area.Compared with model A,the average contact area of t ??he inserts in models B-E increased by 11.8%,14.7%,8.1%,and 32.6%,respectively.(3)Similar to the effect of increasing the contact area,compared with the original model,the contact stress of the optimized model decreased in varying degrees,and the value of model E decreased the most significantly(P<0.05),it is due to good mechanical properties and large porosity of the Diamond lattice that constitutes the D60-type insert.(4)The research results show that the use of porous structure to improve the inserts can improve the elasticity of the inserts and increase its ability to absorb joint impact,for favorable conditions are created for reducing micromotion at the implant-bone interface and improving joint contact behavior.

Objective:To analyze the occupational disease hazards in stone processing enterprises in Weihai City to provide scientific basis for occupational disease prevention.Methods:From January 2021 to December 2022, 107 stone processing enterprises in Weihai City were selected to collect the detection status of occupational hazard factors in the workplace through on-site investigation and on-site monitoring of occupational hazard factors. The diagnostic reports on occupational diseases and suspected occupational diseases of 780 workers were collected through the Occupational Diseases and Hazard Factors Monitoring Information System of the Chinese Center for Disease Control and Prevention, the occupational health monitoring files of the occupational health examination institutions and the information data of the occupational disease diagnosis institutions. The differences between the measurement data were analyzed by Chi-square test or Fisher exact probability method.Results:107 stone processing enterprises were mainly focused on granite processing, and the average free silica content in granite was 32.92% (12.78%-47.84%). The over-standard rate of silica dust was 0.31% (6/1920), and the over-standard rate of noise was 86.20% (1324/1536). Among them, the noise intensity of cutting position was the highest[120.5 dB (A) ]. The over-standard rates of noise in cutting, water grinding, dry grinding (polishing) and material preparation (forklift transportation) were 98.05%, 89.55%, 70.00% and 42.62%, respectively, and the differences were statistically significant ( P<0.05). Among 780 workers, 31 cases (3.97%) of suspected silicosis were detected, and 13 cases (1.67%) were diagnosed with silicosis. 51 cases (6.54%) of suspected occupational noise deafness were detected, and 11 cases (1.41%) were diagnosed with occupational noise deafness. Conclusion:Silicon dust and noise in some positions of stone processing enterprises in Weihai City exceed the standard, and supervision should be strengthened, prevention and control measures should be implemented to protect the occupational health of workers.

Objective:To analyze the occupational disease hazards in stone processing enterprises in Weihai City to provide scientific basis for occupational disease prevention.Methods:From January 2021 to December 2022, 107 stone processing enterprises in Weihai City were selected to collect the detection status of occupational hazard factors in the workplace through on-site investigation and on-site monitoring of occupational hazard factors. The diagnostic reports on occupational diseases and suspected occupational diseases of 780 workers were collected through the Occupational Diseases and Hazard Factors Monitoring Information System of the Chinese Center for Disease Control and Prevention, the occupational health monitoring files of the occupational health examination institutions and the information data of the occupational disease diagnosis institutions. The differences between the measurement data were analyzed by Chi-square test or Fisher exact probability method.Results:107 stone processing enterprises were mainly focused on granite processing, and the average free silica content in granite was 32.92% (12.78%-47.84%). The over-standard rate of silica dust was 0.31% (6/1920), and the over-standard rate of noise was 86.20% (1324/1536). Among them, the noise intensity of cutting position was the highest[120.5 dB (A) ]. The over-standard rates of noise in cutting, water grinding, dry grinding (polishing) and material preparation (forklift transportation) were 98.05%, 89.55%, 70.00% and 42.62%, respectively, and the differences were statistically significant ( P<0.05). Among 780 workers, 31 cases (3.97%) of suspected silicosis were detected, and 13 cases (1.67%) were diagnosed with silicosis. 51 cases (6.54%) of suspected occupational noise deafness were detected, and 11 cases (1.41%) were diagnosed with occupational noise deafness. Conclusion:Silicon dust and noise in some positions of stone processing enterprises in Weihai City exceed the standard, and supervision should be strengthened, prevention and control measures should be implemented to protect the occupational health of workers.

Objective To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization (MR) approach. Methods Summary data for exposure factors and outcome were obtained from different genome-wide association studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted (IVW) method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results. Results The random-effects model of IVW analysis showed that heel bone mineral density (OR=0.986;95% CI,0.974 to 0.998;P=0.023) as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density (OR=1.031;95% CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density (OR=1.014;95% CI,0.973 to 1.057;P=0.505),and forearm bone mineral density (OR=1.011;95% CI,0.935 to 1.094;P=0.775) as outcome datasets showed no causal effect with bronchial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results. Conclusion MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone mineral density in patients with bronchial asthma to timely detect and intervene osteoporosis.

BACKGROUND: Changes in thyroid hormone levels are commonly recognized characters among the elderly, which were reported to potentially influence incident frailty. Therefore, we examined the cross-sectional associations of thyroid hormones (THs) with frailty as well as the five components characterizing frailty (fatigue, resistance, ambulation, number of illnesses, and loss of weight) among the oldest-old. METHODS: Four hundred and eighty-seven community-dwelling oldest-old from a local community in Haidian District, Beijing, participated in our recruitment campaign between April 2019 and May 2020. The primary outcomes were a definitive diagnosis of frailty according to the FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, Loss of weight) and a positive score for each frailty subdomain. Demographic information (age, sex, marital status, and educational status), comorbidities, and details on the participants' lifestyles were recorded. Serum THs including free triiodothyronin (fT3), triiodothyronine (T3), free thyroxine (fT4), and thyroxine (T4) and thyroid stimulating hormone (TSH) levels were also measured at the beginning of our study. Logistic regressions were conducted to screen for potential risk factors for frailty and its subdomains. RESULTS: Among the total 487 subjects at enrollment, 60 (12.23%) of them were diagnosed with subclinical hypothyroidism and 110 (22.59%) of the total population scored positive for frailty. Logistic regression analyses adjusted for all potential confounders, showed that frailty was significantly associated with the serum TSH concentration (odds ratio [OR]: 1.06), fT3 concentration (OR: 0.54), and subclinical hypothyroidism score (OR: 2.18). The association between fT4 and frailty was absent in our observational study. The fT3/fT4 ratio characterizing peripheral hormone conversion was also tested to be correlated with frailty. CONCLUSION Subclinical hypothyroidism, higher TSH level, lower fT3 level, and decreased fT3/fT4 ratio were all associated with frailty assessed by the FRAIL scale among the community-dwelling oldest-old, suggesting a relevant role of thyroid function in aging. Future longitudinal studies are warranted to determine the casual relationship between thyroid dysfunction and frailty in the oldest-old.
Humans ; Aged, 80 and over ; Aged ; Thyroxine ; Cross-Sectional Studies ; Thyrotropin ; Frailty ; Independent Living ; Triiodothyronine ; Thyroid Function Tests ; Thyroid Hormones ; Hypothyroidism ; Fatigue

Objective:To establish and verify a model to predict histologic chorioamnionitis (HCA) for women during expected management of preterm premature rupture of membranes (PPROM) at 24-34 weeks of gestation.Methods:This retrospective study enrolled 493 pregnant women who were diagnosed with PPROM at 24-33 +6 weeks of gestation and delivered in Peking University Third Hospital from January 1, 2012, to December 31, 2020. They were randomly divided into the modeling set ( n=345) and validation set ( n=148) at a ratio of 7∶3. Basic information, risk factors, clinical treatment, and maternal and infant outcomes were compared between participants with and without HCA using Chi-square test, t test, or Mann-Whitney U test. Multivariate logistic regression analysis was performed to analyze the independent risk factors for HCA. The predictive values of different indexes for HCA were compared and the predictive model was then established and verified using the receiver operating characteristic (ROC) curve and area under curve (AUC). Results:There were no significant differences in the basic information, common risk factors for premature rupture of membranes (PROM), or the use of tocolytics, antibiotics or dexamethasone between women in the HCA and non-HCA groups (all P>0.05). Compared with the non-HCA group, the HCA group showed an earlier onset of PROM [31.3 (24.0-33.9) vs 32.3 (27.0-33.9) gestational weeks, U=4 103.00, P=0.017], longer expected treatment [66.5 (0.7-895.3) vs 18.0 (0.3-1 123.0) h, U=1 791.00, P<0.001] and higher incidence of neonatal asphyxia, sepsis, and intracranial hemorrhage [24.3% (58/239) vs 13.2% (14/106), χ 2=5.44; 9.6% (23/239) vs 2.8% (3/106), χ 2=4.86; 41.0% (98/239) vs 17.9% (19/106), χ 2=17.45; all P<0.05]. Moreover, the positive rate of bacterial culture, C-reactive protein (CRP) level, neutrophil/lymphocyte ratio (NLR), white blood cell (WBC) and neutrophil counts were significantly increased in the HCA group [37.2% (89/239) vs 22.6% (24/106), χ 2=7.10; 8.2 (0.0-273.0) vs 5.0 (0.0-218.9) ng/ml, U=2 419.00; 5.6 (1.2-58.6) vs 4.6 (1.7-18.7), U=2 357.50; 11.9 (4.5-30.0)×10 9/L vs 10.1 (5.8-21.8)×10 9/L, U=4 074.50; 9.5 (2.5-28.1)×10 9/L vs 7.6 (3.5-18.5)×10 9/L, U=4 021.50; all P<0.05], while the lymphocyte count was decreased [1.5 (0.5-3.7)×10 9/L vs 1.6 (0.7-3.9)×10 9/L, U=4 237.00, P=0.017]. CRP level, NLR, the gestational week at the onset of PROM and the duration of expected treatment were independent risk factors for HCA ( OR=1.069, 95% CI: 1.024-1.117; OR=1.192, 95% CI: 1.048-1.356; OR=0.906, 95% CI: 0.867-0.947; OR=1.017, 95% CI: 1.007-1.026). Based on the four risk factors, the predictive model was established and ROC curve was drawn. AUC for evaluating the performance of the predictive model was 0.880, which indicated a clinical significance. Conclusion:The model established based on the four risk factors, which were CRP level, NLR, the gestational week at onset of PROM and the duration of expected treatment, performs well in the prediction of HCA in women with PPROM during expected treatment and has good clinical practical value.

Objective:To investigate the clinical manifestations, risk factors and outcomes of patients with acute cingulate cortex (CC) infarction.Methods:Patients with acute CC infarction admitted to the Department of Neurology, the First Affiliated Hospital of Nanjing Medical University from December 2019 to April 2022 were enrolled retrospectively. According to the location of infarction, they were divided into anterior cingulate cortex (ACC) infarction group and posterior cingulate cortex (PCC) infarction group. The clinical manifestations, stroke risk factors, imaging examination and National Institutes of Health Stroke Scale (NIHSS) score of the patients were analyzed. At one month after onset, the modified Rankin Scale was used to evaluate the short-term outcome.Results:A total of 21 patients with acute CC infarction were enrolled, including 12 males (57.14%), aged 67.14±12.36 years (range, 45-89 years). There were 16 patients (76.19%) with ACC infarction, including 13 (81.25%) unilateral CC infarction. The clinical manifestations were mainly apathy, decreased concentration, and executive dysfunction. There were 5 patients (23.81%) with PCC infarction, all with unilateral onset, mainly manifested as memory loss and visual space disorder. Among the 21 patients, 18 (85.71%) had ≥2 vascular risk factors, and 13 patients (61.90%) had ≥3 vascular risk factors, of which hypertension was most common (90.48%); 19 (90.48%) were caused by atherosclerosis, and 2 (9.52%) were caused by cardiogenic embolism. After treatment, the symptoms of both groups were improved significantly, and there was statistical difference in the NIHSS score before and after treatment ( Z=4.07, P<0.01). During the follow-up, 16 patients (76.19%) had a good outcome, 5 (23.81%) had a poor outcome and no death occurred. Conclusions:ACC and PCC infarction mainly showed different forms of cognitive impairment. If the diagnosis and treatment are timely, the overall outcome of CC infarction is good.