Objective To explore the correlation between thyroid hormones and massive proteinuria in patients with type 2 diabetes mellitus (T2DM). Methods A total of 308 patients with T2DM admitted to 3201 Hospital between June 2020 and June 2025 were selected as the observation group, and another 250 healthy individuals who underwent physical examinations during the same period served as the control group. The thyroid hormones levels [free triiodothyronine (FT₃), thyroid stimulating hormone (TSH), and free thyroxine (FT₄)] were measured and compared between the two groups. Based on whether 24-hour urinary protein quantification was ≥ 3.5 g, the patients in the observation group were divided into a massive proteinuria group and a non-massive proteinuria group. Multivariate logistic regression analysis was used to analyze the factors influencing the occurrence of massive proteinuria in T2DM patients. Pearson method was applied to analyze the relationship of thyroid hormone indicators with severity indicators of massive proteinuria. Results Compared with the control group and the non-massive proteinuria group, FT₃ and FT₄ in the massive proteinuria group were lower, while TSH was higher (P<0.05). Multivariate logistic regression analysis suggested that glycosylated hemoglobin (OR=1.113, 95%CI: 1.045-1.185), TSH (OR=1.123, 95%CI: 1.006-1.253), eGFR (OR=0.894, 95%CI: 0.822-0.973), and FT₃ (OR=0.898, 95%CI: 0.828-0.973) were related factors for the occurrence of massive proteinuria in T2DM patients (P<0.05). Pearson correlation analysis revealed that FT3 and FT4 levels in T2DM patients were significantly negatively correlated with 24-hour urinary protein quantification (r=-0.514, -0.502), while the level of TSH was positively correlated with 24-hour urinary protein quantification (r=0.486) (P<0.001). Conclusion In T2DM patients, low FT3 and eGFR levels and high TSH and glycosylated hemoglobin levels are related factors for the occurrence of massive proteinuria, and thyroid hormone levels are significantly associated with the severity of massive proteinuria.

OBJECTIVE To evaluate the cost-effectiveness of acalabrutinib， zanubrutinib， and ibrutinib as first-line treatments for patients with chronic lymphocytic leukemia （CLL）. METHODS A partitioned survival model was developed to simulate the 10-year disease progression of treatment-naive CLL patients. The model used a 4-week cycle length， and an annual discount rate of 4.5% was applied to both costs and health outcomes. Relevant clinical trial literature was systematically reviewed， and survival data for each treatment strategy were extracted. Using the ibrutinib arm from the RESONATE-2 trial as the anchor arm， an anchored indirect comparison approach was performed to estimate the relative treatment effects of acalabrutinib group and zanubrutinib group versus ibrutinib group. Survival curves for progression-free survival and overall survival for each treatment strategy were generated by combining the relative efficacy estimates with the survival data from the anchor arm. Quality-adjusted life year （QALY） were used as the model outcome measure. The incremental cost-effectiveness ratio and incremental net monetary benefit （INMB） were calculated to assess the economic value of the three treatment regimens. The willingness-to-pay （WTP） threshold was set at twice the 2025 per capita gross domestic product of China， corresponding to 199 330 yuan/QALY. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analyses were conducted to evaluate the robustness of the base-case results. RESULTS In the base-case analysis， compared with ibrutinib group， both acalabrutinib group and zanubrutinib group demonstrated cost-saving and health-improving advantages. The INMBs were 149 361.37 yuan for acalabrutinib group and 194 783.94 yuan for zanubrutinib group， indicating that both strategies were dominant over ibrutinib. One-way sensitivity analysis showed that drug prices， hazard ratios between treatment strategies， and utility values were the major factors influencing the results. Probabilistic sensitivity analysis demonstrated that when the WTP threshold was below 450 000 yuan/QALY， acalabrutinib group and zanubrutinib group regimens consistently had higher probabilities of being cost-effective than ibrutinib group. Scenario analyses showed that acalabrutinib group and zanubrutinib group remained cost-effective compared with ibrutinib group under alternative assumptions， including different anchor arms， high-risk patient cohorts， and an extended 20-year time horizon. CONCLUSIONS Compared with ibrutinib， zanubrutinib and acalabrutinib can provide greater economic value as first-line treatments for CLL， with zanubrutinib demonstrating a more pronounced cost-effectiveness advantage.

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 investigate the feasibility of flight fatigue being detected via photoplethysmography (PPG) and regional cerebral oxygen saturation (rScO 2) in order to address the challenges posed by flight fatigue during prolonged or multiple consecutive flights. Methods:A total of 16 healthy male volunteers were enrolled. A wireless cerebral oximetry monitor headband was employed to collect PPG and rScO 2 data from the forehead while a multi-lead physiological data acquisition system was used concurrently to record three-lead electrocardiograms (ECGs). After 18 h of sleep deprivation, each volunteer performed a flight-simulating task, which was divided into 4 stages: the baseline period (T1), relaxation period (T2), early fatigue period (T3) and severe fatigue period (T4). Five-minute data was collected from each stage for analysis using AcqKnowledge 6.0. Heart rate (HR) and 3 HR variability (HRV) metrics, namely standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and low frequency to high frequency power ratio (LF/HF), were computed independently from both ECG and PPG traces. The mean rScO 2 value for each stage was used to represent the cerebral oxygen saturation during that stage. The intra-class correlation coefficient (ICC) was employed to assess the consistency of the measurements, and the differences in HR and HRV indicators of the volunteers in the 4 stages of the experiment were analyzed. Results:The HR measured by ECG and PPG was highly consistent across the 4 stages among the 14 volunteers ( ICC=0.951, 0.963, 0.962, 0.963, P=0.013, 0.011, 0.021, 0.015), so were SDNN, RMSSD and LF/HF values ( ICC=0.935-0.983, all P<0.05). HR values calculated with either method showed significant differences across the 4 stages in the 14 volunteers ( F=21.63, 20.52, P=0.007, 0.008). HR gradually declined from T1 to T4, and was significantly lower at T4 than at T1 ( P=0.011, 0.009). There were significant differences in SDNN ( F=22.31, 24.26, P=0.006, 0.003), RMSSD ( F=22.30, 22.26, P=0.006, 0.006), and LF/HF ( F=20.37, 25.13, P=0.009, 0.002) across the 4 stages among the 14 volunteers. SDNN and RMSSD kept increasing as fatigue was intensified, while LF/HF decreased correspondingly. Statistically significant differences were found in SDNN, RMSSD and LF/HF values between T4 and T1 (all P<0.01). rScO 2 measured during the flight-simulating trial also differed significantly across the 4 stages ( F=21.39, P=0.007). rScO? at both T3 and T4 was significantly lower than at T1 ( P=0.009, 0.007). Conclusions:PPG can replace ECG for monitoring HR and HRV indicators under flight fatigue. Furthermore, the combination of PPG with rScO 2 monitoring allows for earlier detection of flight fatigue. This study is expected to offer a user-friendly and non-invasive approach to management of pilot fatigue.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

Objective:To investigate the feasibility of flight fatigue being detected via photoplethysmography (PPG) and regional cerebral oxygen saturation (rScO 2) in order to address the challenges posed by flight fatigue during prolonged or multiple consecutive flights. Methods:A total of 16 healthy male volunteers were enrolled. A wireless cerebral oximetry monitor headband was employed to collect PPG and rScO 2 data from the forehead while a multi-lead physiological data acquisition system was used concurrently to record three-lead electrocardiograms (ECGs). After 18 h of sleep deprivation, each volunteer performed a flight-simulating task, which was divided into 4 stages: the baseline period (T1), relaxation period (T2), early fatigue period (T3) and severe fatigue period (T4). Five-minute data was collected from each stage for analysis using AcqKnowledge 6.0. Heart rate (HR) and 3 HR variability (HRV) metrics, namely standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and low frequency to high frequency power ratio (LF/HF), were computed independently from both ECG and PPG traces. The mean rScO 2 value for each stage was used to represent the cerebral oxygen saturation during that stage. The intra-class correlation coefficient (ICC) was employed to assess the consistency of the measurements, and the differences in HR and HRV indicators of the volunteers in the 4 stages of the experiment were analyzed. Results:The HR measured by ECG and PPG was highly consistent across the 4 stages among the 14 volunteers ( ICC=0.951, 0.963, 0.962, 0.963, P=0.013, 0.011, 0.021, 0.015), so were SDNN, RMSSD and LF/HF values ( ICC=0.935-0.983, all P<0.05). HR values calculated with either method showed significant differences across the 4 stages in the 14 volunteers ( F=21.63, 20.52, P=0.007, 0.008). HR gradually declined from T1 to T4, and was significantly lower at T4 than at T1 ( P=0.011, 0.009). There were significant differences in SDNN ( F=22.31, 24.26, P=0.006, 0.003), RMSSD ( F=22.30, 22.26, P=0.006, 0.006), and LF/HF ( F=20.37, 25.13, P=0.009, 0.002) across the 4 stages among the 14 volunteers. SDNN and RMSSD kept increasing as fatigue was intensified, while LF/HF decreased correspondingly. Statistically significant differences were found in SDNN, RMSSD and LF/HF values between T4 and T1 (all P<0.01). rScO 2 measured during the flight-simulating trial also differed significantly across the 4 stages ( F=21.39, P=0.007). rScO? at both T3 and T4 was significantly lower than at T1 ( P=0.009, 0.007). Conclusions:PPG can replace ECG for monitoring HR and HRV indicators under flight fatigue. Furthermore, the combination of PPG with rScO 2 monitoring allows for earlier detection of flight fatigue. This study is expected to offer a user-friendly and non-invasive approach to management of pilot fatigue.

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.

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.