1.Effects of hawthorn leaves flavonoids on angiotensin Ⅱ-induced cardiac hypertrophy by regulating miR-21a-5p
Lin-Yan TIAN ; Ran ZHU ; Ju-Ping DAI ; Jia-Jia WANG ; Bin ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2182-2186
Objective To explore the effect and mechanism of hawthorn leaves flavonoids(HLF)on angiotensin Ⅱ(Ang Ⅱ)-induced myocardial hypertrophy.Methods The H9c2 cells were divided into control group(normal culture),model group(100 nmol·L-1 Ang Ⅱ for 24 h),experimental-L,-M,-H groups(received 100 nmol·L-1 Ang Ⅱ for 24 h,then treated with 25,50 and 100 mg·L-1 HLF for 24 h,respectively),anti-miR-NC and anti-miR-21a-5p groups(transfected with anti-miR-NC and anti-miR-21a-5p,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h),miR-NC+high-dose and miR-21a-5p+high-dose group(transfected with miR-NC and miR-21a-5p mimics,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h+100 mg·L-1 HLF for 24 h).The cell viability was detected by cell counting kit-8.The cell apoptosis was measured by flow cytometry.The expression levels of miR-21a-5p was assessed by quantitative real-time polymerase chain reaction.The expression levels of cyclooxygenase-2(COX2)and prostaglandin E2(PGE2)was measured by Western blot.Results The cell viabilities of control,model group experimental-H groups were 1.03±0.09,0.51±0.05 and 0.93±0.08;cell apoptosis rates were(7.69±0.61)%,(23.04±1.82)%and(9.43±0.71)%;the expression levels of miR-21a-5p were 1.00±0.09,2.43±0.18 and 1.09±0.08;the relative expression levels of COX2 protein were 0.42±0.03,0.85±0.08 and 0.40±0.04;the relative expression levels of PGE2 protein were 0.34±0.03,0.75±0.07 and 0.35±0.03;the differences of above indexes were statistically significant between the model group and the control and experimental-H groups(all P<0.05).The cell viabilities of anti-miR-NC,anti-miR-21a-5p,miR-NC+high dose and miR-21a-5p+high dose groups were 0.52±0.04,1.12±0.08,0.94±0.09 and 0.57±0.04;the cell apoptosis rates were(23.04±1.82)%,(9.86±0.73)%,(9.47±0.64)%and(24.96±1.94)%;the expression levels of miR-21a-5p were 1.00±0.10,0.43±0.04,1.00±0.09 and 2.12±0.18;the relative expression levels of COX2 protein were 0.86±0.05,0.39±0.04,0.41±0.03 and 0.78±0.07;the relative expression levels of PGE2 protein were 0.74±0.06,0.38±0.07,0.36±0.02 and 0.71±0.05.Compared the anti-miR-21a-5p group with the anti-miR-NC group,compared the miR-21a-5p+high-dose group with the miR-NC+high-dose group,the differences of above indexes were statistically significant(all P<0.05).Conclusion HLF can inhibit Ang Ⅱ-induced myocardial hypertrophy by regulating the expression of miR-21a-5p and COX2/PGE2 pathway.
2.Investigation of the relationship between metformin and sarcopenia-related traits based on Mendelian randomization
Yue ZHU ; Yinghui JU ; Yuying YANG ; Menglin WANG ; Rui WU
China Pharmacy 2024;35(22):2793-2798
OBJECTIVE To investigate the relationship between metformin and sarcopenia-related traits. METHODS Based on the data from publicly genome-wide association study-related databases, using single nucleotide polymorphisms strongly associated with metformin as instrumental variables, the two-sample Mendelian randomization (MR) analysis methods [inverse variance weighting (IVW) method, MR-Egger regression method and weighted median estimator method] were employed to investigate the relationship between metformin and three sarcopenia-related traits (low grip strength, muscle mass and walking speed). Cochran’s Q test was used to assess heterogeneity, MR-Egger intercept test was used to detect horizontal pleiotropy, and leave-one-out analysis was performed for sensitivity analysis. RESULTS The results of IVW method showed that metformin use was significantly associated with an increased risk of low grip strength (β=1.550, 95%CI was 0.389-2.711, P=0.009) and reduced limb muscle mass (right leg lean body mass: β=-0.665, 95%CI was -1.018--0.312, P<0.001; left leg lean body mass: β=-0.710, 95%CI was -1.049--0.371,P<0.001; right arm lean body mass: β=-0.471, 95%CI was -0.890--0.053, P=0.027; left arm lean body mass: β=-0.463, 95%CI was -0.865--0.061, P=0.024),but was not associated with walking speed. The results or causal effects of the other two methods are consistent with it. The Cochran’s Q test indicated some degree of heterogeneity in the result of this study. No horizontal pleiotropy was detected by the MR-Egger intercept test. The sensitivity analysis suggested that the results of this study were stable. CONCLUSIONS Metformin may increase the risk of sarcopenia.
3.Mechanism of peimine improving chronic obstructive pulmonary disease induced by lipopolysaccharide combined with cigarette smoke in mice
Pei CHEN ; Xiao-Ju CHEN ; Zhu-Man DU ; Cao-Hui WANG
Acta Anatomica Sinica 2024;55(2):215-221
Objective To investigate the effects and mechanisms of peimine(PME)on chronic obstructive pulmonary disease(COPD)in mice.Methods The mice were randomly divided into 4 groups(20 mice in each group),control group,PME group,chronic obstructive pulmonary disease group and treatment group.Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke.The effects of PME on COPD model mice was analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on COPD model mice were analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on inflammatory factor tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting.The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium(DHE)staining and Western blotting.The effects of PME on nuclear factor kappa-B(NF-κB)pathway and nuclear factor erythroid 2-related factor 2(Nrf2)pathway were analyzed by protein immunoblotting.Results Compared with the COPD group,PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice,and the wet/dry weight ratio of lung tissue was significantly reduced.Compared with the control group,the levels of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced.In addition,compared with the control group,the protein expression of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced.Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2)protein in COPD group was significantly lower than that in control group,while PME treatment could improve the level of superoxide dismutase protein.The analysis of MDA content in lung tissue showed that compared with the COPD group,the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment.Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα)and the transfer of NF-κB p65 to the cell nucleus,and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1)in the lung tissue of mice treated with PME significantly increased.Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.
4.Latent tuberculosis infection among close contacts of positive etiology pul-monary tuberculosis in Chongqing
Rong-Rong LEI ; Hong-Xia LONG ; Cui-Hong LUO ; Ben-Ju YI ; Xiao-Ling ZHU ; Qing-Ya WANG ; Ting ZHANG ; Cheng-Guo WU ; Ji-Yuan ZHONG
Chinese Journal of Infection Control 2024;23(3):265-270
Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83%.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P<0.05);infection rate presented increased trend with the increase of age and BMI(both P<0.001),and decreased trend with the increase of education(P<0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95%CI:1.031-3.693),age 55-64 years old(OR=2.473,95%CI:1.279-4.781),other occupations(OR=0.530,95%CI:0.292-0.964),teachers(OR=0.439,95%CI:0.242-0.794),students(OR=0.445,95%CI:0.233-0.851),junior high school education or below(OR=1.412,95%CI:1.025-1.944),BMI<18.5 kg/m2(OR=0.762,95%CI:0.586-0.991),co-living with indicator cases(OR=1.621,95%CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95%CI:1.083-1.540)were the influential fac-tors for LTBI(all P<0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.
5.Acromegaly with pregnancy: A case report and review of literature
Jianghua JU ; Huijuan ZHU ; Linjie WANG ; Hongbo YANG ; Yong YAO ; Lian DUAN
Chinese Journal of Endocrinology and Metabolism 2024;40(1):68-72
This article reports the diagnosis and treatment of a case of acromegaly in a pregnant patient who took bromocriptine during pregnancy and delivered successfully. A retrospective summary of the clinical data and treatment outcomes before and after two pregnancies of the patient is provided. The patient took bromocriptine during the second pregnancy, and her condition remained stable. A baby girl was delivered by caesarean section at full term. The article suggests that pregnancy in acromegaly patients, after the stabilization of the condition, can lead to favorable outcomes. The use of dopamine receptor agonists during pregnancy does not increase adverse events during the perinatal period.
6.Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China
Lei WANG ; Jie SHAO ; Wenhong DONG ; Shuangshuang ZHENG ; Bingquan ZHU ; Qiang SHU ; Wei CHEN ; Lichun FAN ; Jin SUN ; Yue GAO ; Youfang HU ; Nianrong WANG ; Zhaohui WANG ; Tingting NIU ; Yan LUO ; Ju GAO ; Meiling TONG ; Yan HU ; Wei XIANG ; Zhengyan ZHAO ; Meng MAO ; Fan JIANG
Chinese Journal of Pediatrics 2024;62(5):416-422
Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.
7.Proteomic profiling and functional analysis of differentially expressed proteins in lung cancer coexistent with pulmonary tuberculosis
Wendi ZHOU ; Jiamin LIN ; Daichen JU ; Qi WANG ; Jialou ZHU ; Ning SU ; Jinxing HU
The Journal of Practical Medicine 2024;40(13):1814-1821
Objective This study aims to analyze the proteomic characteristics of peripheral blood in patients with lung cancer coexistent with pulmonary tuberculosis(LC-PTB),identify the differential proteins compared with lung cancer(LC)patients,and conduct functional analysis on these proteins.Methods The study included 8 LC-PTB patients and 10 LC patients.The LC patients were newly diagnosed and confirmed by pathology and did not receive any anti-tumor treatment before,while the PTB patients were Mycobacterium tuberculosis positive at the time of sampling.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was applied to perform proteomic mass spectrometry to assess the differential proteins,and then functional analysis was conducted via bioinformatics.Results A total of 5,185 proteins were detected between two groups.Through differential expression screening,190 proteins(58 upregulated and 132 downregulated)were identified to be differentially expressed.Subcellular localization analysis revealed that the differential proteins were mainly concentrated in the cytoplasm,nucleus,and extracellular matrix.KEGG pathway and GO analysis showed the roles of differential proteins in biological processes including immune response,metabolism,and secretion regulation.Protein interaction network analysis highlighted the importance of SORT1,SAR1B,RPS6KB1,VWF,SHC1,SRPRB,CTSD,TARDBP,RPLP0,PSMA2,RPS6,XPO1,PRKACB,and HLA-DRB1 in LC-PTB.Additionally,the expression changes in proteins like ADA2,MAP3K1,and GLS2 might be closely associated with the development of LC-PTB.Conclusions The proteomic profile comprehensively described the proteomic characteristics of LC-PTB and identified numerous differentially expressed proteins,which could provide further clues for research on biological mechanism of LC-PTB.
8.Application of high-throughput drug sensitivity testing in children with relapsed and refractory acute leukemia
Wen-Jing QI ; Xue-Ju XU ; Bai LI ; Tao WANG ; Guang-Yao SHENG ; Ping ZHU ; Chun-Mei WANG
Chinese Journal of Contemporary Pediatrics 2024;26(10):1093-1100
Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.
9.Effect of endoscopic prebiopsy forceps on the detection rate of polyps in the right semicolon
Weizhao WANG ; Mengxian JU ; Haihang ZHU ; Jun LIU ; Lu WANG ; Chaowu CHEN ; Haina CHAI ; Weiwei HAN ; Chao SUN
China Journal of Endoscopy 2024;30(8):31-35
Objective To investigate the effect of endoscopic prebiopsy forceps on the detection rate of polyps in the right semicolon.Method Clinical data of 148 patients diagnosed and treated from March 2022 to December 2022 who were detected as polyps in the right semicolon by general electronic colonoscopy were collected,and clinical data of the patients who underwent endoscopic prebiopsy forceps were re-examined and the patients underwent endoscopic treatment within 1 month.The differences in general data,polyp number detected,polyp size,morphology and pathological diagnosis between the two groups were analyzed and compared.Results 168 polyps were detected in the right semicolon in the general colonoscopy group,and 41 polyps were missed in reexamination using endoscopic prebiopsy forceps,with a missed diagnosis rate of 19.62%.The detection rate of<5 mm polyps was higher in the endoscopic prebiopsy forceps group than that of general colonoscopy group,the difference was statistically significant(P<0.05).The polyps in the two groups were mainly wide-basal type,and the pathological properties were mainly tubular adenoma,there was no statistical significance among all groups(P>0.05).No complications such as bleeding and perforation occurred in the two groups.Conclusion Endoscopic prebiopsy forceps can significantly improve the detection rate of polyps in the right semicolon,in particular,the intraoperative search for disappeared preoperatively identified intestinal polyps,as well as smaller diameter intestinal polyps,which is worthy of further clinical promotion.
10.Harmonization of 18F-FDG PET brain imaging based on ComBat method: a pilot study
Fangyang JIAO ; Dan WANG ; Yuhua ZHU ; Jiaying LU ; Zizhao JU ; Qian XU ; Jingjie GE ; Tao HUA ; Ping WU ; Kuangyu SHI ; Yihui GUAN ; Chuantao ZUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):412-416
Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

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