1.Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway.
Weijie NI ; Yajie ZHAO ; Jinxin SHEN ; Qing YIN ; Yao WANG ; Zuolin LI ; Taotao TANG ; Yi WEN ; Yilin ZHANG ; Wei JIANG ; Liangyunzi JIANG ; Jinxuan WEI ; Weihua GAN ; Aiqing ZHANG ; Xiaoyu ZHOU ; Bin WANG ; Bi-Cheng LIU
Chinese Medical Journal 2025;138(2):193-204
BACKGROUND:
Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD.
METHODS:
We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data.
RESULTS:
Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes.
CONCLUSIONS
Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals
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MicroRNAs/metabolism*
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Angiotensin II/toxicity*
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Mice
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Renal Insufficiency, Chronic/chemically induced*
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Mice, Knockout
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Disease Models, Animal
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Male
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Signal Transduction/genetics*
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LIM Domain Proteins/genetics*
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Mice, Inbred C57BL
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Cell Line
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Humans
2.A comparative study of two single-stage oral mucosal substitution urethroplasty (Kulkarni and Asopa) in the surgical treatments of lichen sclerosus urethral strictures.
Xiang WAN ; Hai-Jun YAO ; Min-Kai XIE ; Jian-Shu NI ; Da-Jun GAO ; Zhong WANG ; Bin XU ; Da-Chao ZHENG
Asian Journal of Andrology 2023;25(6):719-724
Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male
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Humans
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Urethral Stricture/etiology*
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Retrospective Studies
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Constriction, Pathologic/surgery*
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Lichen Sclerosus et Atrophicus/surgery*
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Treatment Outcome
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Urologic Surgical Procedures, Male/methods*
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China
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Urethra/surgery*
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Postoperative Complications/etiology*
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Mouth Mucosa
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Diabetes Mellitus/etiology*
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Anticoagulants
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Coronary Disease
3.Diagnosis and treatment strategy of penoscrotal avulsion injury based on AAST penoscrotal injury grade
Xiang WAN ; Xiaomin REN ; Dachao ZHENG ; Minkai XIE ; Jianshu NI ; Zhong WANG ; Bin XU ; Haijun YAO
Journal of Modern Urology 2023;28(7):573-575
【Objective】 To explore the emergency treatment of penoscrotal avulsion injury based on the American Association for Surgery and Trauma (AAST) penoscrotal injury grade. 【Methods】 Data of 30 patients with penoscrotal avulsion injury treated in our hospital with in-situ suture, skin grafting or skin flap during Oct.2003 and Dec.2017 were reviewed. 【Results】 Among the 30 patients, 29 received emergency surgery, including in-situ suturein 15 grade Ⅰ-Ⅲ cases, skin graft in 8 grade Ⅳ-Ⅴ cases, and skin flap in 6 cases;1 case received delayed operation due to wound infection on admission. In the perioperative period,25 cases had more than 90% wound healing, 3 cases had 70% wound healing after wound dressing change, and 2 cases had complete necrosis. Second-stage skin graft yielded satisfactory penoscrotal appearance. 【Conclusion】 According to the specific conditions of patients, reasonable surgical methods can be selected. For grade Ⅰ-Ⅲ patients, in-situ suture can be used, while for grade Ⅳ-Ⅴ patients, wound condition, age, fertility and other factors should be taken into consideration so as to preserve the function of testis to the maximum extent.
4. Apigenin inhibits liver fibrosis through PDK1/AKT signaling pathway in mice
Xin-Dong CHEN ; Pei-Yao YAN ; Jia-Ni KUANG ; Tao SUN ; Biao HUANG ; Yuan QIN ; Wei-Long ZHONG ; Kai-Liang QIAO
Chinese Pharmacological Bulletin 2022;38(7):1010-1016
Aim To evaluate the therapeutic effect of apigenin on liver fibrosis in mice anrl the pharmacologi¬cal mechanism.Methods Carbon tetrachloride ( CC14) -induced liver fibrosis mouse model was estab¬lished.The mice were divided into six groups of con¬trol, model, silibinin(55 mg • kg 1 • d 1 ) , apigenin in high dosage (60 mg • kg 1 • d 1 ) , apigenin in mid¬dle dosage( 30 mg • kg 1 • d 1 ) and apigenin in low dosage( 15 mg • kg 1 • d 1 ).The general life status, body weight and liver coefficient of the mice in every group were recorded.HE staining, Masson staining, immunohistochemistry and Western blot were used to e- valuate the effect of apigenin on the pathological chan¬ges, the markers related to epithelial-mesenchymal transition and signaling pathways of liver tissues.Re¬sults In CCI4-induced liver fibrosis mice, middle and high-dosage of apigenin could improve the general life status, increase body weight, decrease liver coeffi¬ cient, and significantly improve liver lesions.Middle and high-dosage of apigenin significantly increased the expression of the epithelial marker protein E-cadherin and significantly decreased the expression of the mes¬enchymal marker protein Vimentin in liver tissues of mice with the disease.The further results showed that middle and high-dosage apigenin could significantly in¬hibit the expression of phosphorvlated PDK1 and phos- phorvlated AKT protein in liver tissues of model mice.Conclusions Apigenin can inhibit EMT by inhibiting PDK1/AKT signaling pathway, which plays an anti-fi- brosis role.The apigenin has the potential to be further developed as a drug to protect the liver and treat liver fibrosis.
5.UGT1A1 gene mutations in Chinese Dong neonates in Sanjiang, Guangxi.
Xuan YAO ; Dan-Ni ZHONG ; Yun-Cong PENG
Chinese Journal of Contemporary Pediatrics 2022;24(7):792-796
OBJECTIVES:
To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates.
METHODS:
A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced.
RESULTS:
In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05).
CONCLUSIONS
UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.
Asians/genetics*
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China
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Exons
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Glucuronosyltransferase/genetics*
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Humans
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Hyperbilirubinemia, Neonatal/genetics*
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Infant, Newborn
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Mutation
6.Innovation and exploration of diversified teaching patterns for Biochemical Reaction Engineering under the new engineering education background.
Benwei ZHU ; Fang NI ; Qiang XIONG ; Zhong YAO ; Yun SUN
Chinese Journal of Biotechnology 2021;37(7):2571-2580
Biochemical Reaction Engineering is a professional discipline with emphasis on both theory and practice. It is the core course in the curriculum provision for students majoring in bioengineering and plays an important role in the cultivation of professional talents. However, there are so much theory knowledge, such as formulas and deduction, that students showed poor efficiency in their study. Herein, to cater the objective command of innovative talents under new education background, and to improve the practical teaching efficiency and the students' enthusiasm as well as the practical innovation capability, the teaching team innovated and explored the teaching pattern, the teaching method as well as the teaching technologies. The teaching efficiency has been remarkably improved by introducing the virtual simulate technology, the micro-lecture, the case teaching pattern attempts and the scientific platform, which can be used as reference by other peers.
Bioengineering
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Curriculum
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Humans
;
Students
7. Diagnostic value of water swallow test and simple two-step swallowing provocation test for aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)
Ni LIU ; Ze-guang ZHENG ; You-xia LI ; Jie-ying HU ; Li-hong ZHONG ; Yao-yao FAN ; Rong-chan CHEN
Chinese Journal of Practical Internal Medicine 2019;39(10):904-908
OBJECTIVE: To explore the value of water swallow test(WST)and simple two-step swallowing provocation test(SSPT)in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS:87 hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease were recruited from the First Affiliated Hospital of Guangzhou Medical University during the period between December 2014 to December 2015. RESULTS: The number of patients of grade1,2,3,4 and 5 of water swallow test successively were 44,39,4,0 and 0. Patients with positive aspiration by the first-step(water injection of 0.4 mL)and the second-step(water injection of 2.0 m L)were 16 and 0. Patients with positive aspiration by radionuclide imaging was 35. Comparison of radionuclide imaging, the rate of missed diagnosis applying water swallow test was high 37.3%(31/83). Both the water swallow test and simple two-step swallowing provocation test have poor consistency with radionuclide imaging in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(McNemar consistency test P=0.00).CONCLUSION: There is a high rate of missed diagnosis applying water swallow test and simple two-step swallowing provocation test to diagnosis aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and combined use of multiple assessment methods can reduce the missed diagnosis rate of aspiration.
8.Research on the correlation between uric acid levels and thyroid nodules and gender differences
Yao LIU ; Ziwei LIN ; Chunjun SHENG ; Dajin ZOU ; Zhongwei LYU ; Huixiong XU ; Yikun ZHU ; Yun HUANG ; Ni ZHONG ; Zhao JIA ; Qing WEI ; Shen QU
Chinese Journal of Endocrinology and Metabolism 2017;33(5):377-381
Objective To explore the correlation between thyroid nodules and uric acid levels and to find their gender differences.Methods A total of 68 056 subjects in a regional medical physical examination center of Shanxi Province from January 2013 to June 2015 were enrolled in this study.All the participants′ general information and parameters were recorded.Thyroid nodules were detected by color Doppler ultrasonography.Results The total prevalence of thyroid nodule was 35.5%, 30.7% in males and 40.0% in females.The prevalence of single nodule was 50.1%, and multiple 49.9%.Compared with no nodule group, thyroid nodule group tended to be older, with higher BMI, and with a worse metabolic status(all P<0.01).The uric acid levels were lower[(352.37±78.14 vs 357.70±77.51) μmol/L, P<0.01] in thyroid nodule group in male and higher[(260.22±61.91 vs 253.91±59.18) μmol/L, P<0.01] in female.Conclusion Thyroid nodules may be associated with metabolism and inflammation.In males, hyperuricemia group had lower, while in females, hyperuricemia ones were with a higher prevalence of thyroid nodules.
9.An investigation and analysis on the implementation situation of the performance salary system of primary healthcare institutions in Zhejiang Province
Qi-Sheng GAO ; Li-Hua HUANG ; Ni-Ni WANG ; Tang-Biao SHEN ; Yao-Hong ZHONG
Journal of Preventive Medicine 2016;28(10):996-999
Objective To learn the main problems of performance salary system in primary healthcare institutions after the implement of recent performance salary system guiding opinion in Zhejiang Province.Methods Purposive sampling method was used to separately select 2 counties from high,average and poor economic level regions in Zhejiang Province. Questionnaire survey was conducted among 100 leaders of 84 primary healthcare institutions which the number of staffs is larger than 20.The survey contents included demographic characteristics and the assessment of performance appraisal and performance salary system,which embraced workload,the change of work income and enthusiasm,the incentive function, component ratio and existing problem of performance salary system.Results The average income general increased, however,the staffs working enthusiasm should be further improved.Some problems still exist,such as the public health funds were brought into the total performance salary,and the gross payroll levels were low as well as the performance salary was lack of increasing mechanism.The TCM was the prior development business and contribute most to the revenue and expenditure surplus of primary healthcare institutions.Conclusion The performance salary system should be further improved and the operating effect evaluation in phases and stages should be developed.The decoction pieces should be selled without added profit,and the service ability of primary traditional Chinese medicine should be further strengthened.
10.Characteristics of serum lipid metabolism in patients with autoimmune pulmonary alveolar proteinosis.
Yan LI ; Xin-Lun TIAN ; Yao-Song GUI ; Ai-Ping MA ; Xue LI ; Ni ZENG ; Peng ZHANG ; Yong-Zhong ZHAN ; Guo-Zhen LI ; Kai-Feng XU
Acta Academiae Medicinae Sinicae 2014;36(6):645-649
OBJECTIVETo study the serum lipid panels in consecutive autoimmune pulmonary alveolar proteinosis(APAP)patients and analyze their relationship with anti-granulocyte macrophage-colony stimulating factor(GM-CSF)antibody and other markers.
METHODSThirty-two non-diabetic APAP patients were enrolled in the study. Serum lipids of these patients and 100 healthy volunteers were tested after an overnight fasting. Anti-GM-CSF antibody levels were measured with enzyme-linked immunosorbent assay. The correlation of serum lipids with lactate dehydrogenase,carcinoembryonic antigen,pulmonary function,and artery blood gas parameters were analyzed.
RESULTSTotal cholesterol and low-density lipoprotein cholesterol levels [(5.54±0.99)and(3.73±0.83)mmol/L respectively] were significantly higher in APAP patients than in healthy volunteers [(5.05±0.97)and(3.17±0.89)mmol/L respectively](all P<0.05). High-density lipoprotein cholesterol(HDL-C)level of the APAP group [(1.10±0.18)mmol/L ]was significantly lower than that of the healthy group(P<0.05). Low-density lipoprotein/HDL and total cholesterol/HDL ratios in the APAP group(3.47±0.90 and 5.14±1.12 respectively)were significantly higher than those in the healthy group[(2.63±0.87)and(4.18±1.12)](all P<0.05). There was no significant difference in triglyceride level between the two groups(P>0.05). HDL-C level was negatively correlated with alveolar-arterial oxygen pressure difference(r=-0.436,P<0.05)and positively correlated with arterial oxygen saturation(r=0.459,P<0.05). None of the lipid markers correlated with serum anti-GM-CSF antibody levels(all P>0.05).
CONCLUSIONSAPAP patients were likely to suffer from disturbed lipid metabolism,which was correlated with disease severity to some degree. Lipid markers deserved more attention in the management of APAP patients.
Antibodies ; blood ; Autoimmune Diseases ; epidemiology ; metabolism ; Biomarkers ; blood ; Cholesterol ; blood ; Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor ; metabolism ; Humans ; Lipid Metabolism ; Lipids ; blood ; Lipoproteins, LDL ; blood ; Lung ; physiopathology ; Pulmonary Alveolar Proteinosis ; epidemiology ; metabolism

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