1.Methimazole-induced agranulocytosis and other hematologic damages: Bone marrow characteristics and literature review
Yuanlin LUO ; Pan MA ; Jie ZHENG ; Liya FAN ; Hui GUO ; Bao ZHANG ; Bingyin SHI ; Yayi HE
Chinese Journal of Endocrinology and Metabolism 2024;40(3):219-227
Objective:To retrospectively analyze the bone marrow characteristics of methimazole-induced agranulocytosis and other hematologic damage, and to explore its correlation with clinical features and prognosis.Methods:The bone marrow and clinical parameters of 20 patients of Graves′ disease diagnosed with methimazole-induced agranulocytosis at the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2022 were collected. The intergroup differences in bone marrow characteristics and granulocyte recovery time were analyzed. Differences in peripheral blood and bone marrow characteristics between patients with single agranulocytosis and pancytopenia were compared. Besides, literature review of the bone marrow characteristics of methimazole-induced hematologic diseases was conducted.Results:Compared to patients with bone marrow characteristics of granulocyte and precursor maturation disorders(Type Ⅱ), patients with aplastic marrow(Type Ⅰ) had significant decreases in the proportions of granulocytes in all phases( P<0.05). Patients with bone marrow characteristics of Type Ⅰ had a significant increase in the proportion of the lymphocyte system [51.00%(41.50%, 75.50%) vs 22.00%(14.00%, 35.00%), P=0.002], and got a longer to recovery time [(6.58±1.68)d vs(3.71±1.60)d, P=0.003]; Correlation analysis suggested the granulocyte to erythrocyte ratio was negatively correlated with the granulocyte recovery time( r=-0.520, P=0.023), and the proportion of the bone marrow lymphocyte was positively correlated with granulocyte recovery time( r=0.622, P=0.004). Compared to patients with single agranulocytosis, patients with pancytopenia had a markedly longer hospital stay duration [(27.14±5.27)d vs(14.15±7.36)d, P=0.001]. Literature review suggestsed that methimazole may cause various degrees of damage to blood system and bone marrow. Conclusion:Methimazole can induce a variety of hematologic damages. Analysis of bone marrow characteristics can aid in further prognosis assessment. Clinicians should be vigilant about potential hematologic adverse reactions when using methimazole and promptly diagnose and treat them to prevent serious consequences.
2.Development of the Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses and its reliability and validity
Meng LI ; Jiayue LIU ; Qian LIANG ; Meng ZHAO ; Qianqian YAO ; Bingyin SHI
Chinese Journal of Modern Nursing 2024;30(11):1450-1456
Objective:To develop the Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses and test its reliability and validity.Methods:From January to June 2019, the questionnaire item pool was constructed through literature review, and 13 experts were included in two rounds of Delphi consultation using purposive sampling. In July 2019, convenience sampling was used to select 50 clinical nurses from the surgical ward of the First Affiliated Hospital of Xi'an Jiaotong University as the research subject. A preliminary survey was conducted to form an initial Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses. From August to September 2019, 110 clinical nurses from this ward were selected as the research subject again, and the questionnaire was subjected to item screening and reliability and validity testing.Results:The final Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses included five dimensions of factors influencing blood glucose abnormalities, hazards of blood glucose abnormalities, preoperative and postoperative nursing observation points, emergency treatment of perioperative critical conditions, and key points for perioperative blood glucose management, with a total of 19 items. In the two rounds of consultation, the positivity coefficients of experts were both 100.00% (13/13), the authority coefficient of experts was 0.88, and the coefficients of variation for two rounds of consultation were 0 to 0.30 and 0 to 0.17. Exploratory factor analysis extracted five common factors, with a cumulative variance contribution rate of 66.70%. The Cronbach's α coefficient of the total questionnaire was 0.92, the test-retest reliability coefficient was 0.97, and the scale-level content validity index was 0.98.Conclusions:The Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses has good scientific and practical significance, and can be used as an effective tool to evaluate the perioperative blood glucose management knowledge among surgical nurses.
3.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.
4.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.
5.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.
6.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.
7.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.
8.Practice of the hospital emergency management in fighting against the outbreak of COVID-19 from the aspects of man, machine, material, method, environment and monitoring
Hongmei YAO ; Fan DING ; Jingyuan GAO ; Qing YE ; Ling LEI ; Chen WANG ; Bingyin SHI
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(3):381-384,388
In fighting against the outbreak of coronavirus disease 2019 (COVID-19), focusing on the six key points of man, machine, material, method, environment and monitoring in quality management, our hospital took a series of effective measures in advance to intervene in the key factors that affected the quality of emergency management of public health emergencies. With the development of the epidemic situation, they were further improved with continuous evaluation and adjustment. The emergency response ability and emergency management quality of our hospital have been greatly improved and patients’ safety has been ensured.
9.Directional differentiation and identification of bone marrow-derived dendritic cells in BALB/C mice
Wenxu ZHOU ; Xiaoyan WU ; Bingyin SHI ; Ning NI ; Chenguang DING ; Zhihui GUAN ; Yazhuo JIANG ; Heli XIANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(2):219-224
【Objective】 To establish an effective method for acquiring bone marrow-derived dendritic cells (DCs) from BALB/C mice in vitro and to establish a reservoir of DC precursor cells. 【Methods】 CD117+ hematopoietic stem cells (HSCs) were isolated and purified from bone marrow of BALB/C mice by immunomagnetic beads separation system (MACS), and then amplified in vitro with mouse stem cell factor (SCF) and interleukin-3 (IL-3). HSC was induced to differentiate into DCs by adding granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and IL-4. Different cytokines (tumor necrosis factor-alpha or IL-10) were added to control the maturity of dendritic cells. Then the morphology (electron microscopy), surface molecular markers (FACS method) and cytokine secretion level (ELISA method) were identified. 【Results】 ① The purity of CD117 + HSC isolated and purified by MACS system was over 95%. ② SCF plus IL-3 could effectively stimulate HSC amplification. ③ The morphology of mature DC (mDC) and immature DC (imDC) was significantly different under light and scanning electron microscopy. ④ In the expressions of surface markers CD40, CD80, CD86, I-A/I-E, there were significant differences between imDC group and mDC group (P<0.01). ⑤ After LPS stimulation, the secretion of IL-12 in imDC group did not change significantly (P=0.064), while the secretion of IL-12 in mDC group increased significantly (P=0.009). LPS and TNF-α had a synergistic effect in stimulating DC maturation. 【Conclusion】 Specific combinations of cytokines can effectively induce the differentiation of bone marrow HSCs into DCs in BALB/C mice, and can control the maturity of DCs. This study makes it possible to use gene modified dendritic cells in GD immunotherapy.
10.Sitagliptin compared with glimepiride combined with metformin as an initial therapy in newly diagnosed diabetes patients with severe hyperglycaemia: A randomized controlled non-inferiority study
Mingqian HE ; Jingya WANG ; Mei DENG ; Bingyin SHI ; Jing SUI
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(1):86-92,98
【Objective】 To investigate the efficacy and safety of sitagliptin combined with metformin versus glimepiride combined with metformin in newly diagnosed type 2 diabetes patients with severe hyperglycaemia. 【Methods】 A randomized controlled and non-inferiority trial was carried out. A total of 129 newly diagnosed type 2 diabetes patients with severe hyperglycaemia [FPG≥200 mg/mL (11.1 mmol/L) and HbA1c≥9.0%] were enrolled and numerally randomly assigned to two groups. The patients received sitagliptin combined with metformin (n=66) or glimepiride combined with metformin (n=63) for 4 weeks and then metformin alone for another 8 weeks. Glycaemic control, weight changes and β-cell insulin secretory capacity were investigated to demonstrate the efficacy and safety of these two treatments. 【Results】 Mean HbA1c reduction was 4.03% in sitagliptin group and 4.13% in glimepiride group after 3 months of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HbA1c reduction difference between the two groups was -0.648%, which was more than -0.65%, suggesting that the predefined statistical criterion for non-inferiority was achieved. FPG decreased significantly after one month of intervention in both groups (P<0.05). Significant reduction in the time of reaching euglycemia, FPG and weight decrease was observed in sitagliptin group than glimepiride group (P<0.05). The FPG control rate FPG<110 mg/mL (6.1 mmol/L) was higher in sitagliptin group than in glimepiride group (P<0.05). After the 3-month follow-up, FPG, HbA1c and incidence of hypoglycemia showed no significant differences in the two groups, while weight loss and BMI changes showed significant differences in sitagliptin group compared with glimepiride group (P<0.05). No significant differences in β-cell insulin secretory indexes were observed in the two therapy groups (P>0.05). 【Conclusion】 Our study provided evidence that sitagliptin combined with metformin in newly diagnosed diabetes patients with severe hyperglycaemia showed better outcomes in glycaemic remission compared with glimepiride for those who refused insulin injection.

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