1.CircSLC8A1_005 Inhibits the Fibrotic Phenotype of Cardiac Fibroblasts by Encoding Protein
Yating HU ; Yuan GAO ; Huayan WU ; Yu LIANG ; Hui LI ; Jindong XU ; Yupeng LIU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):35-44
ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes, collagen type I alpha 1 chain (Col1a1), collagen type Ⅲ alpha 1 chain (Col3a1) and smooth muscle actin alpha 2 (Acta2), in mouse cardiac fibroblasts (mCFs) were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay, respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site (IRES) in circSLC8A1_005. CircSLC8A1_005-translated protein, SLC8A1-605aa, and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation (RIP) was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 (Sod2) mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs, and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku, which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 (Sod2) expression, but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA, and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein, and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.
2.Analysis of drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023
Pengfang GAO ; Yanying CHEN ; Yanlei GE ; Xiaoli DU ; Huan XING ; Jiachen LI ; Yuelong LI ; Yating TANG ; Xiao HAN ; Juan LI ; Zhigang CUI ; Haijian ZHOU ; Aiying DONG
Chinese Journal of Preventive Medicine 2024;58(3):306-314
Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.
3.Molecular characteristics and drug susceptibility analysis of Streptococcus agalactiae from respiratory specimen sources
Xiao HAN ; Xinyi GONG ; Beibei MIAO ; Huan XING ; Zeliang LIU ; Pengfang GAO ; Yuelong LI ; Jiachen LI ; Yating TANG ; Yanlei GE ; Aiying DONG ; Juan LI
Chinese Journal of Preventive Medicine 2024;58(6):891-897
To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.
4.Analysis of drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023
Pengfang GAO ; Yanying CHEN ; Yanlei GE ; Xiaoli DU ; Huan XING ; Jiachen LI ; Yuelong LI ; Yating TANG ; Xiao HAN ; Juan LI ; Zhigang CUI ; Haijian ZHOU ; Aiying DONG
Chinese Journal of Preventive Medicine 2024;58(3):306-314
Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.
5.Molecular characteristics and drug susceptibility analysis of Streptococcus agalactiae from respiratory specimen sources
Xiao HAN ; Xinyi GONG ; Beibei MIAO ; Huan XING ; Zeliang LIU ; Pengfang GAO ; Yuelong LI ; Jiachen LI ; Yating TANG ; Yanlei GE ; Aiying DONG ; Juan LI
Chinese Journal of Preventive Medicine 2024;58(6):891-897
To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.
6. Pathogenic mechanism and research progress of adipocytokines in endometrial cancer
Yitong MA ; Jianhong MA ; Yating GAO ; Chang LIU ; Yitong MA ; Jianhong MA ; Yating GAO ; Chang LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1315-1320
Endometrial carcinoma (EC) is one of the most common gynecologic tumors, and its incidence and mortality are increasing.The prognosis is usually favorable when the disease is diagnosed at an early stage. However, the prognosis for patients with recurrence and metastasis is relatively poor. As one of the risk factors for EC, the complex and widespread oncogenic role of obesity in EC has been validated, then the oncogenic and pro-carcinogenic mechanisms of adipocytokines secreted by adipose tissue in EC have attracted continuous attention. This review highly summarizes and concludes the previous relevant literature on the role of adipocytokines in endometrial cancer and the progress of research,and elucidates the correlation between adipocytokines and the occurrence risk, stage grading, and long-term prognosis of EC, as well as their signaling pathways and mechanisms of action in the development of EC. All this information will likely contribute to the development of novel molecular markers in EC, the discovery of new therapeutic targets, and the study of related targeted drugs, which may in turn break the current dilemma of early screening, early diagnosis, and treatment of recurrent and metastatic patients in EC in the future, resulting in an improvement of the long-term prognosis of patients with EC.
7.Establishment and Evaluation of Rat Model for Chronic Obstructive Pulmonary Disease with Lung-spleen Qi Deficiency
Huanzhang DING ; Di WU ; Qinjun YANG ; Haoran XU ; Huimin CI ; Fan WU ; Jiabing TONG ; Yating GAO ; Jie ZHU ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):47-55
ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease (COPD) model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS) along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank, model, and low- (L-FXY), medium- (M-FXY), and high-dose (H-FXY) Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke, with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling, the L-FXY, M-FXY, and H-FXY groups were administrated with Sennae Folium infusion at 5, 10, and 20 g·kg-1, respectively, and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions (body mass, food intake, fecal water content, and anal temperature) and behaviors (grip strength test and tail suspension test) of rats in different groups were examined. The lung function, lung histopathology, D-xylose, amylase, and gastrin levels in the serum, interleukin(IL)-1β and IL-6 levels in the alveolar lavage fluid, levels of T-lymphocyte subsets (CD4+, CD8+, and CD4+/CD8+) in the peripheral blood, and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group, both the M-FXY and H-FXY groups exhibited reduced body mass and food intake (P<0.01) and increased fecal water content (P<0.01). The anal temperature in the H-FXY group was lower than that in the blank group (P<0.01). The grip strength decreased in the modeling groups compared with the blank group (P<0.01), and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups (P<0.05, P<0.01). Compared with the blank group, the modeling groups showed reduced 0.3 second forced expiratory volume (FEV0.3), FEV0.3/forced vital capacity (FVC)(P<0.01), thickening of bronchial walls, proliferation of goblet cells, and the presence of emphysematous changes. In terms of gastrointestinal function, the M-FXY and H-FXY groups had lower levels of D-xylose, gastrin, and α-amylase than the blank group (P<0.01). Regarding the immune and inflammatory indices, the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group (P<0.01). Compared with the blank group, the modeling groups presented lowered CD4+ level (P<0.01) and CD4+/CD8+ ratio (P<0.05, P<0.01) in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid (P<0.01) than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke, intratracheal instillation with LPS, and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose (10 g·kg-1) Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.
8.Effectiveness of a multifaceted intervention for the improvement of nutritional status and nutrition knowledge of children in poverty-stricken areas in Shaanxi Province,China
Zhao CAI ; Ma LU ; Gao LIWANG ; Wu YAN ; Yan YATING ; Peng WEN ; Wang YOUFA
Global Health Journal 2022;6(3):156-163
Objectives:Compare the differences between the intervention and control groups in changes of primary outcomes(body mass index[BMI]and waist-to-height ratio[WHtR])and secondary outcomes(nutrition knowledge of children and parents),from baseline to the 6-and 12-month follow-ups;examine the associations of changes in nutrition knowledge of children and their parents with children's changes in BMI and WHtR.Data sources:Data collected from four schools in two poverty-stricken counties in northern Shaanxi Province in 2020-2021.Methods:A multifaced intervention program targeted children(promoting healthy diet and nutrition education)and their parents(promoting nutrition knowledge)was conducted in the interventional group.Four schools,with two in each group,were randomly allocated to the intervention or control group,with 814 eligible children aged 7.1 to 12.8 years.The control group conducted myopia promotion.Differences in changes of BMI and WHtR between groups were compared with t-test.Mixed-effects model was used to examine the associations between changes in nutrition knowledge of children and parents with changes in children's BMI and WHtR.Results:At the 6-month follow-up,the difference in changes in BMI between the intervention and control groups was 0.4 kg/m 2(P<0.001).At the 12-month follow-up,the difference in changes in BMI and WHtR between intervention and control groups was 0.1 kg/m2(P<0.001)and 0.01 kg/m2(P<0.001).In the intervention group,the nutrition knowledge awareness rate of children increased from 16.9%(69/409)at baseline to 21.3%(87/409)at 6-month,and 22.7%(93/409)at 12-month.The awareness rate of nutrition knowledge of parents also fluctuated,from 5.6%(23/409)to 6.6%(27/409)and 5.4%(22/409).However,the difference in changes in nu-trition knowledge between intervention and control groups was non-significant.The 6-month follow-up changes in children's nutrition knowledge scores were negatively associated with changes in BMI in girls(β=-0.26,95%confidence interval[CI]:-0.38 to-0.14,P<0.001),while positively associated with changes in WHtR in boys(β=0.003,95%CI:-0.0002 to 0.005,P=0.035).The 12-month follow-up changes in children's nutrition knowledge scores were positively associated with changes in children's WHtR(β=0.003,95%CI:0.0004 to 0.01,P=0.018).Conclusions:The intervention strategies did not reduce the BMI and WHtR of children,and the nutrition knowl-edge of children and parents increased after the intervention in intervention group.Changes in nutrition knowl-edge of children and their parents are associated with changes in children's BMI or WHtR.Interventions with a new focus on obesity are needed to help improve children's nutritional status in poverty-stricken areas in Shaanxi Province of China.
9.Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD: A promising drug Potentilla discolor Bunge.
Longshan JI ; Qian LI ; Yong HE ; Xin ZHANG ; Zhenhua ZHOU ; Yating GAO ; Miao FANG ; Zhuo YU ; Robim M RODRIGUES ; Yueqiu GAO ; Man LI
Acta Pharmaceutica Sinica B 2022;12(9):3529-3547
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and metabolic stress-induced liver injury. There are currently no approved effective pharmacological treatments for NAFLD. Traditional Chinese medicine (TCM) has been used for centuries to treat patients with chronic liver diseases without clear disease types and mechanisms. More recently, TCM has been shown to have unique advantages in the treatment of NAFLD. We performed a systematic review of the medical literature published over the last two decades and found that many TCM formulas have been reported to be beneficial for the treatment of metabolic dysfunctions, including Potentilla discolor Bunge (PDB). PDB has a variety of active compounds, including flavonoids, terpenoids, organic acids, steroids and tannins. Many compounds have been shown to exhibit a series of beneficial effects for the treatment of NAFLD, including anti-oxidative and anti-inflammatory functions, improvement of lipid metabolism and reversal of insulin resistance. In this review, we summarize potential therapeutic effects of TCM formulas for the treatment of NAFLD, focusing on the medicinal properties of natural active compounds from PDB and their underlying mechanisms. We point out that PDB can be classified as a novel candidate for the treatment and prevention of NAFLD.
10.Status and associations of nutritional and dietary behaviors of school age children in poor areas of western China
WU Yan, GAO Liwang, MA Lu, LI Chao, ZHAO Cai, LIU Min, YAN Yating, BAI Jing, ZHAO Li, WANG Youfa
Chinese Journal of School Health 2022;43(12):1787-1790
Objective:
To investigate the status of nutrition and dietary behaviors and their associations in school age children in poor areas of western China, to provide clues for sustainable improvement strategies of malnutrition among primary school students in rural revitalization.
Methods:
A total of 1 887 school age students from 3 poverty stricken counties in Shaanxi and Sichuan provinces were investigated by physical examination and questionnaire survey during October to December in 2020. Mixed effects model was used to analyze associations between nutritional status and dietary behaviors.
Results:
The prevalence of stunting, wasting, overweight and obesity, and central obesity among 1 887 students were 1.8%, 6.6%, 27.7%, 24.5%, respectively, and the differences between two provinces were statistically significant ( χ 2=94.76, 46.05, 109.96, 80.50, P <0.05). The prevalence of overweight and obesity of students in Shaanxi and Sichuan were 32.8% and 4.9%, respectively. The prevalence of stunting and wasting were 0.4% and 4.7% in Shaanxi, and 8.1% and 14.7% in Sichuan, respectively. Among 1 160 students with complete dietary data, the proportions of students who ate breakfast, eggs, and milk daily were low, and eating breakfast daily was negatively associated with overweight and obesity( OR =0.26, P <0.05), and eating out and eating in canteen were positively associated with wasting( OR = 2.51, 2.82, P <0.05).
Conclusion
School age children in poor areas of western China are facing double burden of malnutrition, and there are significant regional differences. Future targeted interventions should be made to improve these students nutritional status.


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