ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Objective:To investigate personal exposures to nitrogen oxides(NOX)and nitrogen di-oxide(NO2)and the influence of baseline personal characteristics,living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai.Methods:In this panel study,91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study.The study was conducted in summer and winter.The participants were followed for three times with an interval of at least two weeks.Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic.Twenty-seven participants completed follow-up visits in both seasons.We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity in-formation through questionnaire/diary.The linear mixed model was used to analyze the associations be-tween potential influencing factors and personal NOX and NO2 exposure levels.Results:There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities.The ave-rage 24 h personal exposures to NO2 and NOX(volume fraction)in Tianjin participants were 18.0 x 10-9 and 26.2 × 10-9 in summer,and 31.0 x 10-9 and 54.9 x 10-9in winter,respectively;and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7 x 10-9and 100.0x10-9in summer,and 45.5 x10-9 and 139.2 x 10-9 in winter,respectively.The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city,season,gender,average daily cooking times,and ambient NO2 concentrations measured at fixed-site monitoring stations.In addition to the above factors,the personal NOX exposure levels were also significantly associ-ated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking,average daily home time,cooking energy type,residential distance from main traffic road,and use of kitchen ventilators.Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai,were significantly lower in summer than that in winter,and were significantly and positively associated with ambient NO2 concen-trations measured at fixed-site monitoring stations.In addition,personal NOX exposure levels were signifi-cantly lower in females than in males,and personal NO2 exposure levels were significantly positively asso-ciated with average daily cooking times and significantly inversely associated with average daily home time.For every interquartile range(IQR)increase(12.7 × 10-9)in ambient NO2,the personal NO2 exposure levels increased by 27.5％(95％CI:17.0％-38.9％),and personal NOX exposure levels in-creased by 16.1％(95％CI:7.1％-25.8％).Conclusion:Season,city and ambient NO2 concentra-tions are significant influencing factors of personal exposure levels of NO2and NOX At the same time,the personal exposures levels of NO2 are also affected by lifestyle factors.Our study provides scientific evi-dence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m³ increase of gestational exposure to PM_2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1^st-2^nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O₃ exposure during the 1^st week and SO₂ exposure during 6^th-7^th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS This study highlighted that gestational exposure to PM_2.5, O₃, and SO₂ had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.
Infant ; Pregnancy ; Child ; Humans ; Female ; Air Pollutants/analysis* ; Case-Control Studies ; Prenatal Exposure Delayed Effects/epidemiology* ; Heart Defects, Congenital/etiology* ; China/epidemiology* ; Particulate Matter/adverse effects* ; Maternal Exposure/adverse effects*

Objective: To investigate the effect of long-term exposure of nitrogen dioxide on the incidence of hypertension. Methods: From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow-up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self-report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO₂ during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO₂ exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO₂ exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results: The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m². During an average follow-up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m³. After adjusting for age, sex, BMI, family history of hypertension, socio-economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m³ increase of NO₂ was 1.21 (95%CI: 1.18-1.25). Compared with residents aged 60 years and over (HR=1.19, 95%CI: 1.14-1.26), former and current smoking (HR=1.20, 95%CI: 1.14-1.25), and high-frequency fruit consumption (HR=1.17, 95%CI: 1.13-1.21), residents younger than 60 years (HR=1.28, 95%CI: 1.25-1.32), non-smoker (HR=1.23, 95%CI: 1.19-1.27), and low-frequency fruit consumption (HR=1.27, 95%CI: 1.20-1.35) had stronger interaction effect with NO₂ (all P values for interaction<0.05). Conclusion NO₂ exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low-frequency fruit consumption.

Objective To investigate the effect of long?term exposure of nitrogen dioxide on the incidence of hypertension. Methods From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow?up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self?report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m2. During an average follow?up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m3. After adjusting for age, sex, BMI, family history of hypertension, socio?economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m3 increase of NO2 was 1.21 (95%CI:1.18-1.25). Compared with residents aged 60 years and over ( HR=1.19, 95%CI : 1.14-1.26), former and current smoking ( HR=1.20, 95%CI : 1.14-1.25), and high?frequency fruit consumption ( HR=1.17, 95%CI :1.13-1.21), residents younger than 60 years ( HR=1.28, 95%CI : 1.25-1.32), non?smoker ( HR=1.23, 95%CI :1.19-1.27), and low?frequency fruit consumption ( HR=1.27, 95%CI : 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low?frequency fruit consumption.

Objective To investigate the effect of long?term exposure of nitrogen dioxide on the incidence of hypertension. Methods From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow?up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self?report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m2. During an average follow?up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m3. After adjusting for age, sex, BMI, family history of hypertension, socio?economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m3 increase of NO2 was 1.21 (95%CI:1.18-1.25). Compared with residents aged 60 years and over ( HR=1.19, 95%CI : 1.14-1.26), former and current smoking ( HR=1.20, 95%CI : 1.14-1.25), and high?frequency fruit consumption ( HR=1.17, 95%CI :1.13-1.21), residents younger than 60 years ( HR=1.28, 95%CI : 1.25-1.32), non?smoker ( HR=1.23, 95%CI :1.19-1.27), and low?frequency fruit consumption ( HR=1.27, 95%CI : 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low?frequency fruit consumption.

Objective To observe the changes of serum ferritin and 25-(OH) vitamin D3 in patients with diabetic cranial neuropathy.Methods There were 50 patients without diabetic Cranial neuropathy,46 patients with diabetic cranial neuropathy,and 40 cases of normal control group.The changes of serum ferritin and 25-hydroxy vitamin D3 were observed in each group.The correlation between two indexes and the correlation with diabetic cranial neuropathy were analzyzed.Results The serum ferritin levels in diabetic group and diabetic neuropathy group were significantly higher than those in normal control group (P ＜ 0.01),and its level in patients with diabetic cranial neuropathy [(687.54 ± 65.38)ng/ml] was significantly higher than that of patients without diabetic cranial neuropathy [(497.28 ± 46.39) ng/ml,P ＜0.01].The serum 25-(OH) vitamin D3 levels in the diabetic group and diabetic neuropathy group were lower than those in the control group (P ＜ 0.01),and its level in patients with diabetic cranial neuropathy [(26.45 ± 8.93)nmol/l] was significantly less than that of patients without diabetic cranial neuropathy [(37.19-± 9.74)nmol/L,P ＜ 0.01].Serum ferritin levels were positively correlated with 25-(OH) vitamin D3 (r =-0.59,P ＜ 0.01).Multivariate unconditional Logistic regression analysis showed that diabetic neuropathy was negatively correlated with 25-(OH) vitamin D3 (P ＜ 0.05).Conclusions The increases of serum ferritin and 25-(OH) vitamin D3 are closely related to the occurrence and development of diabetic cranial neuropathy,which provides the theoretical basis for clinical intervention therapy.

Objective To investigate the changes of serum ferritin and homocysteine of diabetic patients,to explore its correlation with diabetic gastroparesis.Methods Pure 50 patients with diabetes,50 patients with diabetic gastroparesis,and 50 cases of normal control group were chosen.The serum ferritin levels were measured with chemiluminescence method,the serum homocysteine levels were measured with enzyme linked immunosorbent assay (ELISA) method.The changes of serum ferritin and serum homocysteine in each groups were observed.Its relationship with diabetic gastroparesis was studied.Results For all diabetic patients,the serum ferritin and homocysteine levels were significantly higher than those in normal control group (P ＜ 0.01).Patients with diabetic gastroparesis was higher than those of pure diabetes (P ＜ 0.01).Serum ferritin levels was positively correlated with glycosylated hemoglobin and homocysteine (r =0.62,0.78,P ＜ 0.01).Multi-factor analysis showed that serum ferritin,and homocysteine level was positively associated with diabetic gastroparesis (P ＜ 0.05).Conclusions The increases of serum ferritin and homocysteine levels were closely related to the occurrence and development of diabetic gastroparesis.They can be used as one of parameters of diabetic gastroparesis,and provide theoretical basis for clinical intervention therapy.