OBJECTIVE To investigate the effect of plasma trough concentration of venetoclax and its influencing factors in patients with acute myeloid leukemia （AML）. METHODS After 5 days of venetoclax administration， venous blood samples were collected from AML patients before the next dose. Plasma trough concentrations of venetoclax were determined using high-performance liquid chromatography-tandem mass spectrometry. Spearman correlation was used to assess the correlations between venetoclax plasma trough concentration and various parameters （including patients’ general information， venetoclax-related indicators， liver function indicators， kidney function indicators， and blood routine indicators）. Multiple linear regression analysis was performed to identify independent factors influencing plasma trough concentration of venetoclax. Using efficacy as dependent variable [complete remission （CR）+partial remission （PR） vs. no remission （NR）]， univariate and multivariate binary Logistic regression analyses were conducted to identify factors affecting efficacy. The receiver operating characteristic （ROC） curve was used to evaluate the predictive value of venetoclax plasma trough concentration for clinical efficacy （assessed as CR）. RESULTS A total of 172 venetoclax plasma trough concentration measurements from 101 patients were included in this study. The median plasma trough concentration of venetoclax was 2.38 （1.18， 3.85） μg/mL； the median sampling time for plasma trough concentration of venetoclax was 10 （7， 15） d； the duration of venetoclax use was （34±12） d. Multiple linear regression analysis showed that alkaline phosphatase （ B ＝14.65， 95%CI： 5.35-23.95， P ＝0.002）， total bilirubin （ B ＝－101.71， 95%CI： －197.16 to －6.25， P ＝0.037）， and white blood cell count （ B ＝－106.84， 95%CI： －187.61 to －26.07， P ＝0.010） were independent factors influencing plasma trough concentration of venetoclax. Due to patient attrition during treatment， 114 venetoclax plasma trough concentration measurements from 69 patients were included for efficacy evaluation. The results showed that 46 patients （66.7%） achieved CR， 11 patients （15.9%） achieved PR， and 12 patients （17.4%） were NR. Multivariate binary Logistic regression analysis showed that age， hemoglobin， venetoclax plasma trough concentration， hematocrit， and mean corpuscular hemoglobin were independent factors affecting patient efficacy （ P ＜0.05）. ROC curve analysis showed that the cut-off value of plasma trough concentration of venetoclax for predicting patient efficacy （assessed as CR） was 1.68 μg/mL （AUC＝0.66， 95%CI： 0.54-0.78， P ＝0.014）. CONCLUSIONS There is considerable inter-individual variability in plasma trough concentration of venetoclax among AML patients. Plasma trough concentration of venetoclax is significantly correlated with alkaline phosphatase， total bilirubin， and white blood cell count. Plasma trough concentration of venetoclax is an independent factor affecting patient’s efficacy， and when the cut-off value for predicting CR is above 1.68 μg/mL， better effects may be achieved.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Crohn's disease (CD) is a chronic progressive inflammatory bowel disease. With the introduction of the "treat-to-target (T2T) " concept, the treatment goals for CD have become clearer and more specific. Traditional surgical treatment for CD typically follows a "complication-driven" approach, in which surgery is usually performed only after severe complications, such as bowel obstruction, fistulas, perforation, or cancer have occurred. The emergence of the treat-to-target strategy and the concept of disease clearance has transformed the surgical treatment of CD from a "passive rescue" model to an "active intervention" approach. Treatment goals have shifted from merely addressing complications and improving symptoms to achieving both short and long-term therapeutic objectives within the framework of treat-to-target. Achieving these goals helps to prevent CD-related complications, delay disease progression, reduce the risk of recurrence and malignancy, and improve the quality of life.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

Crohn's disease (CD) is a chronic progressive inflammatory bowel disease. With the introduction of the "treat-to-target (T2T) " concept, the treatment goals for CD have become clearer and more specific. Traditional surgical treatment for CD typically follows a "complication-driven" approach, in which surgery is usually performed only after severe complications, such as bowel obstruction, fistulas, perforation, or cancer have occurred. The emergence of the treat-to-target strategy and the concept of disease clearance has transformed the surgical treatment of CD from a "passive rescue" model to an "active intervention" approach. Treatment goals have shifted from merely addressing complications and improving symptoms to achieving both short and long-term therapeutic objectives within the framework of treat-to-target. Achieving these goals helps to prevent CD-related complications, delay disease progression, reduce the risk of recurrence and malignancy, and improve the quality of life.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

The prevalence of periodontal disease in Chinese population is more than 90％.The present treatment techniques can only control the development of the disease,inducement of bone tissue regeneration is a promising strategy and a challenge for the treatment.Exosomes are multivesicle structures derived from endosomes.More and more studies have been conducted on their application in perio-dontal regeneration.This paper reviews the application of exosome in periodontal regeneration in recent years,which is expected to pro-vide new idea for periodontal regeneration therapy.