1.Exploring Detoxication Mechanism of Dioscoreae Bulbiferae Rhizoma Processed with Phaseoli Radiati Semen Juice Based on Target Organ Ferroptosis
Yaqian DUAN ; Lingling SONG ; Yueyue ZHANG ; Junming WANG ; Minghao LIU ; Yamin LI ; Bingyin LI ; Xiaohui WU ; Yanmei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):70-76
ObjectiveTo investigate the attenuating effect of Dioscoreae Bulbiferae Rhizoma(DBR) processed with Phaseoli Radiati Semen(PRS) juice, and explore the attenuating mechanism based on ferroptosis of the main toxic target organ. MethodSixty male ICR mice were randomly divided into blank group, DBR group, water roasted DBR group(hereinafter referred to as water group), PRS juice-roasted DBR group 1(DBR-PRS 10∶1, stuffy moistening for 40 min, stir-fried at 130 ℃ for 18 min, hereinafter referred to as group 1), PRS juice-roasted DBR group 2(DBR-PRS 10∶1, stuffy moistening for 80 min, stir-fried at 100 ℃ for 14 min, hereinafter referred to as group 2), PRS juice-roasted DBR group 3(DBR-PRS=20∶3, stuffy moistening for 40 min, stir-fried at 160 ℃ for 14 min, hereinafter referred to as group 3). The raw and processed groups of DBR were gavaged with their corresponding 95% ethanol extract at a dose of 3 g·kg-1·d-1, while the blank group was gavaged with an equal volume of 0.5% sodium carboxymethyl cellulose, once a day for 14 consecutive days. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of mouse liver. Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in serum, as well as malondialdehyde(MDA), ferrous ions(Fe2+), reduced glutathione(GSH) and superoxide dismutase(SOD) levels in liver tissue were detected by the biochemical detection. Western blot was used to detect the expression of iron key proteins such as ferritin heavy chain 1(FTH1) and glutathione peroxidase 4(GPX4). ResultHE staining results showed that the liver tissue structure of the blank group was clear, the morphology of hepatocytes was normal, the cytoplasms of hepatocytes in the DBR group and water group were loose and vacuolar, with obvious pathological damages, and the pathologic damages of mice in the group 1-3 were significantly improved. Compared with the blank group, the levels of ALT, AST, MDA and Fe2+ in mice from the DBR group were significantly increased(P<0.01), while GSH and SOD levels were significantly reduced(P<0.01), and the protein expression levels of FTH1 and GPX4 were significantly decreased(P<0.01). Compared with the DBR group, the ALT, AST,MDA and Fe2+ levels of mice in the group 1-3 were significantly reduced(P<0.05, P<0.01), the GSH and SOD levels and the protein expression levels of FTH1 and GPX4 were significantly increased(P<0.01). Compared with the water group, the AST and MDA levels of mice in the group 1-3 were significantly reduced(P<0.05, P<0.01), the SOD level significantly increased(P<0.05, P<0.01), the FTH1 protein expression significantly increased(P<0.01), and the serum ALT level of mice in the group 2-3 significantly reduce(P<0.01), Fe2+ level significantly reduced(P<0.01), GSH level significantly increased(P<0.05, P<0.01), and GPX4 protein expression significantly increased(P<0.05, P<0.01). Among the group 1-3, the group 3 had the best detoxification effect. ConclutionProcessing with PRS juice can reduce the liver injury induced by DBR, and the mechanism may be related to the inhibition of ferroptosis in the liver.
2.Development and validity test of blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia
Meng LI ; Meng ZHAO ; Qian LIANG ; Jiayue LIU ; Qianqian YAO ; Zhenzhen WANG ; Bingyin SHI
Chinese Journal of Diabetes 2024;32(10):756-763
Objective To develop a blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia and test its reliability and validity.Methods The initial questionnaire was formed through literature review,expert consultation,two rounds of Delphi letter consultation,and pre-survey.From August to September 2019,a total of 125 perioperative patients with hyperglycemia who were hospitalized in the surgical ward of the First Affiliated Hospital of Xi'an Jiaotong University were selected as the survey objects by the convenient sampling method.The items of the questionnaire were screened and the reliability and validity were tested.Results A total of 125 questionnaires were distributed and 115 valid questionnaires were returned,with an effective recovery rate of 92.0%.The blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia included five dimensions(17 items in total),including influencing factors and hazards of abnormal blood glucose,key points of preoperative and postoperative nursing observation,perioperative blood glucose control goals,perioperative blood glucose management points,and emergency treatment of perioperative critical conditions.The effective recovery rates for both rounds of inquiry are 100.00%,the expert authority coefficient was 0.880 and the average coefficient of variation was 0.086 and 0.065(P<0.01).Exploratory factor analysis extracted a total of five common factors,and the cumulative variance contribution rate was 79.895%.The Cronbach's α coefficient of the questionnaire was 0.905,the test-retest reliability was 0.955,and the content validity index was 0.968.Conclusions The blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia is scientific and practical,which can be used as an effective tool to evaluate the blood glucose management knowledge level during perioperative period.
3.The regulatory role of the hypothalamus in the thermogenesis of brown and beige adipose tissue
Hongli DU ; Huan YAN ; Bingyin SHI ; Yanan WANG
Chinese Journal of Endocrinology and Metabolism 2024;40(8):719-726
There are three types of adipose tissue: white adipose tissue that stores energy, brown adipose tissue that expends energy, and beige adipose tissue which results from the browning of white adipose tissue. Research has established that adipose tissue is vital for energy metabolism. However, the complex regulatory mechanisms limit the development of effective therapeutic strategies for obesity and related metabolic diseases. This review explores the characteristics and functions of adipose tissue types, emphasizing the role of central hypothalamic nuclei in regulating peripheral adipose tissue function Additionally, it provides a summary and comparison of current research on leveraging brown and beige adipose tissue thermogenesis as a treatment for metabolic diseases, offering insights for the advancement of targeted therapies for obesity and related disorders.
4.Secretory expression of human thyroid stimulating hormone receptor A subunit in sf9 insect cell system
Meng ZHANG ; Kaining ZHANG ; Ziyi CHEN ; Ling WANG ; Liping WU ; Yue WANG ; Bing LIU ; Bingyin SHI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):409-414
【Objective】 To construct the secretory expression system of insect cells to express the secretory TSHR A subunit protein in the ovarian cells of Spotoma oryzae (sf9). 【Methods】 A recombinant plasmid containing the target protein was constructed, and then the positive bacmid was screened out by the blue and white spots experiment. The verified bacmid was transfected into SF9 insect cells to obtain recombinant baculovirus. The virus was amplified, and the titer level was detected by virus plaque assay. Finally, Western blotting was used to identify the expression of the recombinant protein and optimize the expression conditions. 【Results】 During the construction of the protein expression system, PCR identification and sequencing results confirmed the correctness of the sequences of the recombinant plasmid and the recombinant bacmid. After the transfection of the bacmid, the signs of virus budding were observed in sf9 cells. The virus was collected and amplified. The titer of P1 generation virus was 2×107 pfu/m according to the plaque assay. The recombinant protein was identified by Western blotting and confirmed to be exogenous into the culture medium. The optimal condition for virus infection and protein expression was 72 h after the infection when the multiplicity of infection (MOI) was 1. 【Conclusion】 We constructed an insect cell expression system secreting TSHR 22-289 (55 ku), and the protein could be successfully glycolyzed. This system provides a preliminary basis for the construction and production of its industrial platform and also provides a useful tool for studies on TSHR protein and prevention of GO in the future.
5.Rapamycin restores CD4 + T cell subsets imbalance in Graves′ ophthalmopathy mice model
Meng ZHANG ; Ling WANG ; Xi DING ; Mingqian HE ; Ziyi CHEN ; Xiaoyan WU ; Liping WU ; Bingyin SHI ; Yue WANG
Chinese Journal of Endocrinology and Metabolism 2023;39(11):964-973
Objective:To study the effect of rapamycin on the disorder of CD4 + T cell subsets in Graves′ ophthalmopathy(GO) mice, as well as the ophthalmopathy and hyperthyroidism phenotype, providing new possibilities for the treatment of GO. Methods:6-8 weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times. Rapamycin was given by embedding in the feed(14 ppm). The animals were euthanized 4 weeks after the final injection to obtain blood, spleen cells, thyroid glands, and orbital tissue. TT 4, thyrotropin receptor antibody(TRAb), thyroid, and orbital pathologic changes were detected, and the CD4 + T cell subgroup was evaluated by flow cytometry and immunohistochemistry. Results:After final immunization, the mice showed characteristics of GO: increased retrobulbar fibrosis and retrobulbar adipogenesis that indicated ophthalmopathy, increased autoantibodies, and serum total thyroxin that indicated hyperthyroidism. After the intervention of rapamycin, retrobulbar fibrosis and retrobulbar adipogenesis were significantly improved, and the incidence of ophthalmopathy was reduced from 80%-90% to 20%. Moreover, the increase of total thyroxin was reduced from 80% to 20%, and the metabolic condition and thyroid pathology were also improved. Flow cytometry of the spleen, immunohistochemistry of the thyroid and orbital tissue revealed that GO mice exhibited Th1 dominance in Th1/Th2 balance and reduction of Treg cells. After the intervention of rapamycin, flow cytometry showed that the ratio of Th1 and Th17 cells decreased and the ratio of Th2 and Treg cells increased. Immunohistochemistry of thyroid and orbital tissues also confirmed improvement of Th1/Th2 cell imbalance and Treg cell reduction.Conclusion:GO mouse model showed a significant imbalance of CD4 + T cell subsets, and rapamycin could not only regulate the disorder of CD4 + T cell subsets in GO mice, but also effectively improve the phenotype of ophthalmopathy and hyperthyroidism. Therefore, the imbalance of CD4 + T cell subsets is one of the etiological intervention targets of GO, and rapamycin is a potential intervention mode of GO, which can be further explored by randomized clinical studies in the future.
6.Research progress on the regulation of cholesterol metabolism in the treatment of nonalcoholic fatty liver disease
Huan YAN ; Hui GUO ; Bingyin SHI ; Yanan WANG
Chinese Journal of Clinical Nutrition 2022;30(2):87-100
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide nowadays. Given the very complex pathogenesis, there are yet no effective pharmacological agents for the treatment of NAFLD. Accumulating evidence has shown that cholesterol metabolism dysregulation, resulting in excess cholesterol accumulation in the liver and subsequent hepatic inflammation and injury, is one of the most important causes for the occurrence and development of NAFLD. This suggests the application of cholesterol metabolism- targeting therapeutic strategy in NAFLD. This review firstly summarized the pathogenesis of NAFLD, then focused on the regulation of cholesterol metabolism and underlying mechanisms through which excess hepatic cholesterol contributed to NAFLD, and reviewed the research progress on cholesterol-lowering agents aimed at maintaining the cholesterol homeostasis to treat NAFLD, which would provide insights for novel strategies to treat NAFLD in both preclinical studies and clinical settings.
7.Epidemiological Characteristics of syphilis in Kashgar area of Xinjiang Uygur Autonomous Region, 2005-2020
Kare YASEN ; Xiaowang PENG ; Chunmei XIE ; Ping WANG ; Shaofeng JIANG ; Bingyin ZHANG
Chinese Journal of Epidemiology 2022;43(8):1269-1274
Objective:To understand the epidemiological characteristics and trends of syphilis in Kashgar area of Xinjiang Uygur Autonomous Region and provide a basis for formulating syphilis control measures.Methods:A descriptive epidemiological method was used to analyze the epidemiological characteristics of syphilis cases reported in Kashgar from 2005 to 2020, and the Joinpoint 4.8.0.1 software was used to calculate the annual percent change (APC) and perform trend testing.Results:From 2005 to 2020, 75 331 syphilis cases were reported in Kashgar. The number of syphilis cases increased from 720 in 2005 to 4 275 in 2020. The reported incidence increased from 19.57/100 000 in 2005 to 93.86/100 000 in 2020 in two stages. From 2005 to 2014, the reported incidence increased from 19.57/100 000 to 188.17/100 000, with an average annual increase of 28.24%. From 2014 to 2020, the reported incidence decreased from 188.17/100 000 to 93.86/100 000, with an average annual decrease of 12.58%. The reported incidence of primary syphilis, secondary syphilis, tertiary syphilis and fetal-transmitted syphilis increased first and then decreased with time. However, the reported incidence of recessive syphilis has been on the rise. Since 2018, the ratio of recessive syphilis has exceeded that of primary syphilis, becoming the main epidemic type. The incidence ratio of male to female was 0.97∶1 (37 097∶38 234); all age groups had reported cases, with 20-49-year-old group the most, accounting for 55.65% (41 921/75 331) of the total number of reported cases; occupational distribution was dominated by farmers, accounting for 71.15% (53 595/75 331) of all reported cases, and the proportion of farmers was increasing year by year, from 35.00% in 2005 to 79.04% in 2020.Conclusions:The situation of syphilis in Kashgar was serious in 2005-2020. We should strengthen the publicity of health knowledge and health education,especially strengthen the health education and prevention of young and middle-aged people, farmers, women of childbearing age and other key groups. Additional, the screening that raises syphilis ceaselessly even and detects level, accomplish early discovery, standard report and cure, in order to curb the popularity of syphilis.
8.The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65
Xichang WANG ; Haoyu WANG ; Li YAN ; Lihui YANG ; Yuanming XUE ; Jing YANG ; Yongli YAO ; Xulei TANG ; Nanwei TONG ; Guixia WANG ; Jinan ZHANG ; Youmin WANG ; Jianming BA ; Bing CHEN ; Jianling DU ; Lanjie HE ; Xiaoyang LAI ; Yanbo LI ; Zhaoli YAN ; Eryuan LIAO ; Chao LIU ; Libin LIU ; Guijun QIN ; Yingfen QIN ; Huibiao QUAN ; Bingyin SHI ; Hui SUN ; Zhen YE ; Qiao ZHANG ; Lihui ZHANG ; Jun ZHU ; Mei ZHU ; Yongze LI ; Weiping TENG ; Zhongyan SHAN
Endocrinology and Metabolism 2021;36(4):778-789
Background:
Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension.
Methods:
Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017.
Results:
The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years.
Conclusion
The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.
9.Comparison of efficacy and safety of insulin aspart injection Rishulin and NovoRapid for treatment of diabetes: a multicenter, randomized, open-labeled, controlled trial
Weiping JIA ; Yuqian BAO ; Heng MIAO ; Ping TU ; Yu LIU ; Tao YANG ; Wenbo WANG ; Bingyin SHI ; Ming LIU ; Wenjin HUA ; Ningning HOU ; Qiu ZHANG ; Ling HU ; Shuguang PANG ; Jingdong LIU ; Guixia WANG
Chinese Journal of Internal Medicine 2021;60(12):1148-1156
Objective:To compare the efficacy and safety of Tonghua Dongbao′s insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes.Methods:A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment.Results:For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% ( P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % ( P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95% CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% ( P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% ( P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L ( P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L ( P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group ( P=0.320). Ratios of negative to positive were 7.43% and 10.61% ( P=0.360), and ratios of positive to negative were 10.40% and 7.58% ( P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% ( P=0.371), and the incidence of adverse events was 76.60% and 77.70% ( P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions:Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.
10.The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65
Xichang WANG ; Haoyu WANG ; Li YAN ; Lihui YANG ; Yuanming XUE ; Jing YANG ; Yongli YAO ; Xulei TANG ; Nanwei TONG ; Guixia WANG ; Jinan ZHANG ; Youmin WANG ; Jianming BA ; Bing CHEN ; Jianling DU ; Lanjie HE ; Xiaoyang LAI ; Yanbo LI ; Zhaoli YAN ; Eryuan LIAO ; Chao LIU ; Libin LIU ; Guijun QIN ; Yingfen QIN ; Huibiao QUAN ; Bingyin SHI ; Hui SUN ; Zhen YE ; Qiao ZHANG ; Lihui ZHANG ; Jun ZHU ; Mei ZHU ; Yongze LI ; Weiping TENG ; Zhongyan SHAN
Endocrinology and Metabolism 2021;36(4):778-789
Background:
Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension.
Methods:
Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017.
Results:
The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years.
Conclusion
The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

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