1.Effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease model rats
Yu LEI ; Jing LU ; Wenjuan HE ; Jiaying GU ; Dengfeng ZHOU
China Pharmacy 2025;36(8):939-944
OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease (COPD) model rats. METHODS COPD rat model was induced by lipopolysaccharide, and they were randomly divided into model group (COPD group), bumetanide low-dose and high-dose groups (Bumetanide-L group, Bumetanide-H group), bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif (YAP/TAZ) signaling pathway activator group (Bumetanide-H+PY-60 group), with 12 rats in each group. Another 12 normal rats were selected as normal control group (Control group). Thirty minutes before modeling, bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration, the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds (FEV0.3), forced vital capacity (FVC), peak expiratory flow (PEF), FEV0.3/FVC]. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in bronchoalveolar lavage fluid (BALF) were determined; the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β (TGF- β), α -smooth muscle actin (α-SMA) and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group, the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated; the exfoliation of lung epithelial cells, tube wall thickening and the degree of pulmonary fibrosis were alleviated; inflammatory cell infiltration was reduced, and blue collagen deposition was reduced; FEV0.3, FVC, FEV0.3/FVC and PEF were significantly increased, while the lung injury score, levels of TNF-α, IL-6, IL-1β, expression levels of TGF-β, α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased (P<0.05). PY-60 could significantly reverse the improvement effects of bumetanide on above indexes (P<0.05). CONCLUSIONS Bumetanide can alleviate lung injury, inflammatory response and pulmonary fibrosis in COPD rats, and its mechanism is related to inhibiting YAP/TAZ signaling pathway.
2.Evaluation of the Effect for National Centralized Drug Procurement Policy of PPIs in 33 Hospitals in Wuhan
Zhijuan LIN ; Li LIU ; Wenjuan HE ; Zhiliang ZHANG ; Zhaohui GUO ; Ping LIU ; Quan LEI ; Ying XU
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1723-1728
OBJECTIVE
To analyze the use status and development trend of proton pump inhibitors(PPIs) in 33 hospitals in Wuhan, Hubei Province after the implementation of the national centralized drug procurement(NCDP) policy, and to provide reference for promoting the subsequent rational use of NCDP drugs and improving related policies.
METHODS
To make statistics and analysis of purchasing amount of PPIs, defined daily dose system(DDDs), defined daily dose consumption(DDDc) and utilization rate of 33 hospitals in Wuhan in 2019 and 2022.
RESULTS
After the implementation of the NCDP policy, the total purchasing amount of PPIs decreased by 53.6%, DDDs decreased by 15.4%, DDDc decreased by 45.2%, and the utilization rate of PPIs injectable dosage forms decreased by 12.6%. After NCDP, the highest growth rate of oral dosage forms was omeprazole(5.7%), followed by rabeprazole(5.0%), while injectable dosage forms showed a significant difference in utilization rate, with a significant decline in NCDP varieties and a significant increase in non-NCDP varieties. The overall NCDP utilization rate of PPIs in Wuhan was 64.9%, with little difference among hospitals of different grades.
CONCLUSION
The NCDP policy achieves the purpose of reducing the drug cost of patients and improving the accessibility of drugs, and is more optimized in the selection of dosage forms, which is in line with the policy expectations overall; but the quantity and price of PPIs in Wuhan decreased after NCDP, and highlighted a certain tendency in the selection of varieties. In the future, we still need to optimize measures to guide clinical priority in the selection of NCDP drugs, to ensure and improve the implementation of NCDP policy.
3.Study of the effects of dietary patterns on glycemic control in community type 2 diabetic mellitus patients
Liyun LEI ; Li QIN ; Zhanguo WANG ; Jun WANG ; Qun ZHAO ; Chaoqin JI ; Bo CHEN ; Qingjun ZHANG ; Fang ZHOU ; Ming WU ; Jinyi ZHOU ; Wenjuan WANG
Chinese Journal of Epidemiology 2024;45(2):242-249
Objective:To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients.Methods:Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control.Results:Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95% CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95% CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern ( OR=0.71, 95% CI: 0.52-0.98) and fruit-aquatic products-potato patterns ( OR=0.71, 95% CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns ( OR=0.60, 95% CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern ( OR=1.41, 95% CI: 1.03-1.94; OR=1.68, 95% CI: 1.13-2.51) and egg-milk-bean pattern ( OR=1.75, 95% CI: 1.25-2.46; OR=1.56, 95% CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q2 group), egg-milk-bean pattern ( Q3 group)" was higher ( OR=6.79, 95% CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q3 group), egg-milk-bean pattern ( Q2 group), oil-salt pattern ( Q2 group)" had higher control rate of 2 h PBG ( OR=12.78, 95% CI: 1.26-130.05, P=0.031). Conclusions:A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.
4.Two case reports of rare antisynthetase syndrome and literature review
Dongbin JIANG ; Yinli ZHANG ; Wenjuan GUAN ; Lei ZHANG ; Hongling ZENG ; Xin ZHANG ; Shengyun LIU ; Guanmin GAO
Chinese Journal of Rheumatology 2024;28(2):123-126
Objective:To study the clinical and immunological features of two case of rare antisynthetase syndrome (ASS), so as to improve the level of diagnosis and treatment.Methods:Two cases with rare antisynthetase syndrome admitted to the First Affiliated Hospital of Zhengzhou University from July 2020 to August 2022 were collected.Results:The two rare ASS were anti-Zo antibody and anti-Ha antibody positive patients, both of which had interstitial lung disease (ILD) as the main clinical manifestation and positive anti-Ro52 antibody. Two rare antisynthetase autoantibodies manifested cytoplasmic ANA indirect immunofluorescence (IIF) staining pattern, but it is different from the cytoplasmic dense speckled pattern of several common ASS antibodies. After treatment with glucocorticoids and immunosuppressants, case 1 died of respiratory failure due to a long course of disease and late diagnosis, the lung lesions of case 2 improved significantly.Conclusion:When encountering the cytoplasmic ANA fluorescent pattern in ILD patients, especially with anti-Ro52 antibody, it is necessary to screen more myositis specific antibodies to rule out the possibility of rare ASS.
5.Analysis of pathological differences in lupus nephritis between the Li and Han ethnic groups in Hainan
Wenjuan LEI ; Ju CHEN ; Yanyan FENG ; Jun ZHOU
Journal of Chinese Physician 2024;26(5):712-716
Objective:To explore the differences in renal pathological characteristics between Li and Han patients with lupus nephritis (LN) in Hainan region.Methods:A retrospective analysis was conducted on the renal pathological data of 135 patients with systemic lupus erythematosus (SLE) who underwent renal biopsy in the Department of Nephrology and Rheumatology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from January 2013 to December 2023. They were divided into Li ( n=22) and Han ( n=113) patients according to their ethnicity. The SLE disease activity index (SLEDAI-2000), renal pathological classification, glomerulosclerosis, and tubulointerstitial lesions of LN patients from different ethnicities were analyzed. Results:During the follow-up period, there was no statistically significant difference in the incidence rate of end-stage renal disease in LN patients between Li nationality and Han nationality (13.6% vs 7.9%, P=0.656). The SLEDAI-2000 score of Li ethnic LN patients was mainly mild and moderate activity, while Han ethnic LN patients were mainly moderate and severe activity. There was no statistically significant difference in SLEDAI-2000 between the two groups ( P=0.577). The pathological subtypes of LN patients in both Li and Han ethnic groups are mainly Ⅳ/Ⅳ+ Ⅴ. There was no statistically significant difference between the two groups in different pathological subtypes of Ⅰ, Ⅱ, Ⅲ/Ⅲ+ Ⅴ, Ⅳ/Ⅳ+ Ⅴ, and Ⅴ (all P>0.05). There was no statistically significant difference in AI and CI between the two groups (all P>0.05). There was no statistically significant difference in the proportion of glomerulosclerosis between Li and Han LN patients ( P>0.05). However, the acute and chronic renal tubulointerstitial lesions in Li ethnic LN patients are more severe than those in Han ethnic group ( P=0.008 and P=0.038). Conclusions:The incidence rate of end-stage renal disease in LN patients of Li nationality is higher than that in Han nationality. The acute and chronic renal tubular and interstitial lesions in LN patients of Li nationality are more serious than those in Han nationality.
6.Distribution characteristics of pathogenic microorganisms in patients with postoperative incision infection after general surgery and the predictive value of serum LDH and IL-6 for infection
Qiang DENG ; Lei ZHANG ; Liu HE ; Huiting SU ; Wenjuan XU
International Journal of Laboratory Medicine 2024;45(12):1506-1510
Objective To explore the general surgery patients with postoperative incision infection(SSI)of pathogenic microorganism distribution characteristics and serum lactate dehydrogenase(LDH),interleukin(IL)-6 to the predictive value of infection.Methods A total of 100 patients who underwent surgery in the General Surgery Department of the hospital from January 2021 to June 2023 were selected as the research ob-jects.According to the occurrence of postoperative infection,the patients were divided into infection group(28 cases)and non-infection group(72 cases).The basic data of the patients were collected,including age,gender,operation type,operation time,incision type,and incision healing.Bacterial culture and pathogen identification were performed on the incision secretion of patients under sterile conditions.At the same time,the serum LDH and IL-6 levels of the patients on the first and third day after operation were detected,and the differences of LDH and IL-6 levels between the infection group and the non-infection group were compared.Pearson cor-relation analysis was used to analyze the correlation between serum LDH level and IL-6.Multivariate Logistic regression analysis was used to analyze the influencing factors of SSI.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of serum LDH and IL-6 levels for SSI.Results A-mong the 100 patients,28 patients developed SSI,and the infection rate was 28%.There were significant differences in age,operation time,and incision type between the infection group and the non-infection group(P<0.05).The results of bacterial culture showed that a total of 35 strains of bacteria were isolated from the patients in the infection group,of which Gram-positive bacteria accounted for 54.29%and Gram-negative bac-teria accounted for 45.71%,mainly Staphylococcus aureus(14 strains),Pseudomonas aeruginosa(7 strains),and Escherichia coli(5 strains).The serum levels of LDH and IL-6 in the infection group were higher than those in the non-infection group on postoperative days 1 and 3(P<0.05).The serum level of LDH in the in-fection group was positively correlated with IL-6(r=0.512,P<0.001).Multivariate Logistic regression a-nalysis showed that age,operation time,type of incision,and serum LDH and IL-6 levels on postoperative day 3 were independent risk factors for SSI(P<0.05).ROC curve analysis showed that serum LDH and IL-6 lev-els had a high diagnostic efficacy for SSI,with an area under the curve of 0.89 and 0.88,the best cut-off values of 210 U/L and 15 pg/mL,the sensitivity of 82.14%and 85.71%,and the specificity of 78.57%and 80.36%,respectively.Conclusion Staphylococcus aureus and Pseudomonas aeruginosa are the main pathogenic micro-organisms of SSI in general surgical patients.Serum LDH and IL-6 levels can be used as predictors of SSI,which is of great significance for early diagnosis and treatment of infection.
7.Vector flow mapping technique for evaluating left ventricular diastolic function in ovarian cancer patients with postoperative chemotherapy
Chuncui CHEN ; Wenjuan QIN ; Ruimeng TIAN ; Ruoxi CHEN ; Yifei ZHOU ; Lei HUANG ; Xueting GUO ; Guilin LU
Chinese Journal of Interventional Imaging and Therapy 2024;21(8):477-481
Objective To observe the value of vector flow mapping(VFM)technique for assessing changes of left ventricular diastolic function in ovarian cancer(OC)patients who underwent postoperative chemotherapy.Methods Totally 37 OC patients who received postoperative chemotherapy were prospectively enrolled in chemotherapy group,while 40 healthy adults were taken as controls(control group).Routine echocardiography and VFM were performed for chemotherapy group before chemotherapy,after 3 and 6 cycles of chemotherapy,also for controls at enrollment,and comparison was performed between groups before chemotherapy,as well as among different time points within chemotherapy group,and the correlations of VFM results with hemoglobin and routine echocardiographic results in chemotherapy group were analyzed.Results No significant difference of age,body mass,body surface area(BSA),nor hemoglobin level,routine echocardiographic and VFM results before chemotherapy was found between groups(all P>0.05).With the process of chemotherapy,hemoglobin level gradually decreased,the isovolumic relaxation period(IR),atrial systole period(AS)intraventricular pressure difference(IVPD)and intraventricular pressure gradient(IVPG)of the left ventricle gradually increased(adjusted P<0.05),whereas routine echocardiography only showed that the left atrial volume index(LAVI)and the ratio of early mitral inflow velocity and the mean mitral annular early diastolic velocity(E/e')increased after 6 cycles of chemotherapy compared with those pre-chemotherapy(adjusted P<0.05).In chemotherapy group,VFM results in all diastolic subphases were strongly correlated with hemoglobin levels(|r|=0.718 to 0.836,all P<0.05),weakly to moderately correlated with LAVI(|r|=0.375 to 0.525,all P<0.05)and moderately correlated with E/e'(|r|=0.424 to 0.537,all P<0.05).Conclusion The diastolic function of left ventricle was probably damaged in early stage after postoperative chemotherapy in OC patients.VFM might detect slight changes of early diastolic function of left ventricle more sensitively than routine echocardiography.
8.Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming.
Shixin DUAN ; Xinyi LOU ; Shiyi CHEN ; Hongchao JIANG ; Dongxin CHEN ; Rui YIN ; Mengkai LI ; Yuseng GOU ; Wenjuan ZHAO ; Lei SUN ; Feng QIAN
Acta Pharmaceutica Sinica B 2023;13(12):4785-4800
Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
9.Analysis of related factors of emotional and behavioral abnormalities in children with overactivity of bladder
Wenjuan WANG ; Guowei SI ; Yakai LIU ; Ru JIA ; Songyang WANG ; Jing YANG ; Lei LYU ; Yanping ZHANG ; Xiaoping SHANG ; Jianguo WEN
Journal of Modern Urology 2023;28(4):313-317
【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.
10.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.


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