ObjectiveTo evaluate the safety and clinical utilization of traditional Chinese medicine （TCM） formula granules based on real-world data， and to provide evidence for their rational clinical use. MethodsA multicenter， prospective， open-label， observational centralized monitoring study was conducted. Participants who received TCM formula granules in 293 medical institutions throughout China from February 5th， 2020 to May 20th， 2025 were consecutively enrolled. The year of data collection was used as the stratification factor. Demographic characteristics （including sex， age， and concomitant medication use）， information on TCM formula granule use （including mean prescribed dosage and inappropriate use）， and adverse event（AE）/adverse drug reaction（ADR） occurrence and related factors were collected and statistically analyzed. ResultsA total of 42 011 participants were included in the safety set （SS）， with a mean age of （38.34±22.30） years， including 18 693 males and 23 318 females. Among them， 3519 participants （8.38%） had a history of or concomitant diseases. The three most common comorbidities were hypertension （1189 cases， 33.79%）， diabetes mellitus （850 cases， 24.15%）， and coronary heart disease （471 cases， 13.38%）. The top three diagnostic categories were respiratory， thoracic， and mediastinal diseases （7008 cases， 16.68%）， infectious and parasitic diseases （6591 cases， 15.69%）， and gastrointestinal diseases （4580 cases， 10.90%）.Among 41 961 participants with available concomitant medication data， 3332（7.94%） received concomitant medications， and western medicines were the most commonly used concomitant medications （2819 cases， 6.72%）. The mean prescribed dosage of TCM formula granules （expressed as the equivalent dosage of crude herbal pieces） was （158.23±104.86） g in 2020， （131.70±65.84） g in 2021， （130.62±59.96） g in 2022， （86.74±50.61） g in 2023， （118.59±52.01） g in 2024， and （134.38±49.43） g in 2025. The five most frequently prescribed toxic herbs were Kuxingren （Semen Armeniacae Amarum， 2746 cases， 6.54%）， Xixin （Radix et Rhizoma Asari， 2193 cases， 5.22%）， processed Kuxingren （862 cases， 2.05%）， Baiqucai （Herba Chelidonii， 747 cases， 1.78%）， and Wuzhuyu （Fructus Evodiae， 645 cases， 1.54%）. Prescriptions involving incompatible combinations of the "eighteen antagonisms" and the "nineteen mutual inhibitions" were most frequently observed in 2020 （54 cases， 0.503%）， and then decreased markedly， remaining at zero or an extremely low level thereafter. The overall incidence of adverse drug reactions （ADRs） associated with TCM formula granules was 0.057% （24 cases）， indicating a rare occurrence. The annual incidence was 0.028% （3 cases） in 2020， 0 in both 2021 and 2022， 0.065% （5 cases） in 2023， 0.158% （15 cases） in 2024， and 0.226% （1 case） in 2025. Among the 24 patients who experienced ADRs， 15 had inappropriate medication use.Five of the 24 patients used toxic herbs， and all five had inappropriate medication. Multivariate logistic regression analysis showed that no history of drug-related adverse reactions ［OR=0.053， 95%CI（0.006， 0.465）］ and no concomitant medication ［OR=0.315， 95%CI（0.109， 0.911）］ were associated with a lower risk of ADRs. ConclusionTCM formula granules are widely used in clinical practice and exhibit a favorable overall safety. Greater attention should be paid to people with a history of drug-related adverse reactions and those receiving concomitant medications to further improve medication safety.

Objective To analyze the temporal trend of thyroid cancer incidence in China from 1992 to 2021 and evaluate the impact of age,period and cohort on the incidence.Methods Based on the Global Burden of Disease 2021,the trend changes of age-standardized incidence rate(ASIR)of thyroid cancer in China from the period were analyzed,and the obtained data were further analyzed with Joinpoint regression and age-period-cohort analysis.Auto regressive integrated moving average(ARIMA)model was applied to predict the incidence of thyroid cancer in China in the next 20 years.Results The ASIR of thyroid cancer among males was increased from 0.70/100 000 to 2.11/100 000 between 1992 and 2021,with an average annual percent change(AAPC)of 3.93%(95%CI:3.86%～4.00%,P<0.001);For the females,the ASIR was elevated from 1.91/100 000 to 2.87/100 000 in the time,with an AAPC of 1.43%(95%CI:1.36%～1.50%,P<0.001).On the age effect,the overall variation in ASIR among the females was minor,and that in the males reached its peak in the≥85-years-old group,with a rate of 230.51/100 000.Regarding the period effect,the risk of thyroid cancer incidence in the males and females changed with the period and exhibited a temporal increase,and the incidence risk was consistently higher in the males than the females across different periods.Taking the incidence risk during 1992 and 1996 as a reference(RR=1),the males(RR=2.94,95%CI:2.78～3.11)and the females(RR=1.37,95%CI:1.32～1.42)had the highest risk of thyroid cancer in the period from 2017 to 2021.On the cohort effect,the risk of thyroid cancer in both sexes showed an increasing trend with cohort change.When taking the cohort during 1992 and 1996 as a reference(RR=1),the females in the pre-1986 cohort exhibited a higher risk of incidence than the males,but in the post-1996 cohort,the males demonstrated a greater risk of incidence than the females.The males in the 2012-2016 cohort had the highest risk of thyroid cancer when compared to the reference group(RR=2.54,95%CI:1.80～3.57),and the females in the cohort from 1992 to 2016 had higher risk of thyroid cancer than the reference group,though no statistical differences were observed.The ARIMA model prediction analysis found that the ASIR of thyroid cancer in males and females in China would continue to increase from 2022 to 2041,and the ASIR of thyroid cancer in males would reach 2.79/100 000(95%CI:1.96～3.61),and the ASIR of thyroid cancer in females would reach 3.54/100 000(95%CI:3.02～4.06)by 2041.Conclusion Between 1992 and 2021,the ASIR of thyroid cancer in China has exhibited a consistent upward trend,with the females having a higher ASIR than the males.However,the risk of developing thyroid cancer is higher in men who are older and those who were born more recently.In the next 20 years,the incidence of thyroid cancer among both men and women in China is projected to continue to rise,and the situation for prevention and control will be challenging.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Objective To develop and validate a risk prediction model for social dysfunction in middle-aged and elderly patients with ischemic stroke.Methods A non-matched case-control study was conducted among ischemic stroke patients admitted to the neurology department of a tertiary hospital in Tangshan between August 2022 and March 2023.Patients who developed social dysfunction within 3 months after discharge were assigned to a case group,while those without it were assigned to a control group.Multivariate logistic regression was used to identify significant predictors and construct a nomogram-based prediction model.The model's discrimination and calibration were assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Internal validation was performed via bootstrap resampling,and clinical utility was evaluated using decision curve analysis.Results Logistic regression identified the following as significant risk factors for social dysfunction(P＜0.05):male gender,age≥60 years,primary education or below,rural residence,income＜3 000,cognitive impairment,low disability acceptance,poor self-management ability,suboptimal utilization of chronic disease resources,low future-oriented coping,and high cumulative ecological risk.The nomogram achieved an AUC of 0.874,with a sensitivity of 79.4％and specificity of 80.7％.The Hosmer-Lemeshow test indicated good calibration(x2=3.631,P=0.88).Conclusion The developed nomogram provides an effective tool for predicting the risk of social dysfunction in middle-aged and elderly ischemic stroke patients,facilitating early identification of high-risk individuals.

Chronic atrophic gastritis(CAG)is a precancerous lesion of gastric cancer,and its pathogenesis is complicated,with recurrent and prolonged symptoms.Starting from the view of stomach collaterals and sweat pores,the paper analyzed the pathogenesis of CAG,i.e.,stagnation and obstruction of sweat pores,and blood stasis obstructing stomach collaterals.Furthermore,this paper explored the efficacy of wind medicines in treating CAG by opening sweat pores and unblocking stomach collaterals.It is believed that wind medicines are pungent with warm nature,and have the actions of relieving exterior syndrome,regulating qi,elevating yang,unblocking collaterals and dissipating masses,which enable their efficacy on opening sweat pores and unblocking stomach collaterals.In the treatment of CAG,wind medicines are able to open the sweat pores,and the opening of sweat pores promotes the recovery of spleen-stomach function in lifting lucid yang and lowering turbid yin;wind medicines have the actions of directing herbs to the affected meridian or site,and assisting the other Chinese medicines to achieve satisfactory efficacies;wind medicines can also be used for drying dampness,and enhance the efficacy of removing dampness with the help of their actions of opening sweat pores.During the treatment of CAG,the combination of wind medicines can enhance the therapeutic effect of Chinese herbal medicine,and the exploration in this paper will provide reference for traditional Chinese medicine treatment of CAG in clinic.

Objective:To analyze the infection status of Coxsackievirus B group (CVB) in regions affected by sudden unexplained death in Yunnan (referred to as sudden death in Yunnan), and to provide a scientific basis for formulating effective prevention and control strategies.Methods:A cross-sectional survey method was employed. The population from 16 counties (cities, districts, referred to as counties) affected by sudden death in Yunnan Province from 2002 to 2022 and the population from one non-affected county in 2021 and 2022 (control population) were classified into cases of sudden death in Yunnan (7 cases), co-occurring cases (29 cases), high-risk population (1 303 cases), and control population (270 cases). Blood samples were collected from these populations. By using enzyme-linked immunosorbent assay (ELISA), CVB immunoglobulin M (CVB-IgM) antibodies in the acute-phase serum samples of the population in the affected areas were detected, and CVB immunoglobulin G (CVB-IgG) antibodies in the convalescent-phase serum samples were detected. Both types of detections were carried out on the control population, and the test results were analyzed.Results:A total of 1 609 serum samples were tested, including 1 339 samples from the population in the affected areas (923 acute-phase samples and 416 convalescent-phase samples) and 270 samples from the control population. Among the 16 affected counties, positive CVB-IgM antibody results were detected in 9 counties. The overall positive rate of the population in the affected areas was higher than that of the control population [7.80% (72/923) vs. 4.44% (12/270), χ 2 = 40.78, P < 0.001]. The positive rates of the high-risk population in Dayao County and Lufeng City were both higher than that of the control population [(22.22% (22/99), 10.92% (25/229) vs. 4.44% (12/270), χ 2 = 27.37, 7.56, P < 0.05]. Positive CVB-IgG antibody results were detected in 7 counties. The overall positive rate of the population in the affected areas was higher than that of the control population [(4.09% (17/416) vs. 0.74% (2/270), χ 2 = 6.81, P = 0.009]. The positive rates of CVB-IgM and CVB-IgG antibodies in the population of the affected areas in Dayao County [22.22% (22/99), 9.80% (5/51)] were both higher than those of the control population ( P < 0.05). Among the five affected villages in Dayao County, the positive rates of CVB-IgM and CVB-IgG antibodies in the population of Aji Ju Village were the highest [25.49% (13/51), 3/13]. Conclusions:The positive rates of both CVB-IgM and CVB-IgG antibodies in the population of the areas affected by sudden death in Yunnan were higher than those of the control population, indicating that CVB infection occurred during the sudden death events in the above-mentioned affected areas.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Objective:To construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy, to provide a basis for promoting pre-rehabilitation in patients undergoing radical prostatectomy.Methods:Literature analysis was used to search domestic and foreign databases such as China National Knowledge Infrastructure, Wanfang, PubMed, etc, on triple pre-rehabilitation and rapid rehabilitation of patients undergoing radical prostatectomy, with a search time frame from January 1, 2013 to December 31, 2023. The Delphi expert letter consultation was conducted later, and the final draft of the triple pre-rehabilitation intervention program for patients with radical prostatectomy was finally formed.Results:A total of 20 experts completed 2 rounds of inquiries, all were female, with an age of (40.85 ± 5.40) years old. The response rates for the 2 rounds of expert inquiries were both 100%(20/20). The authority coefficients of the experts were 0.87 and 0.90, respectively. Kendall coordination coefficients were 0.11 and 0.21, respectively. The coefficient of variation for each item in the second round of inquiries ranged from 0 to 0.15. The triple pre-rehabilitation intervention program for patients with radical resection of prostate cancer was constructed, including 4 primary indexes, 8 secondary indexes and 25 tertiary indexes.Conclusions:It is scientific, targeted and feasible to construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy based on Delphi method, which can provide clinical basis for pre-rehabilitation of elderly patients undergoing prostate cancer surgery.

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.