1.Diabetic Nephropathy Treatment by Zn Supplementation in a Murine Model of Type 1 Diabetes Mellitus:Potential Role of Nrf2 Signaling Pathway
Lianhong XU ; Weixia SUN ; Wei LIU ; Yanbo LI
Journal of Sichuan University (Medical Sciences) 2025;56(3):613-618
Objective To evaluate the renoprotective effects of zinc(Zn)supplementation in diabetes kidney disease(DKD)and to explore its impact on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Methods A total of 12 male OVE26 mice(spontaneous type 1 diabetes mellitus mice)aged 3 months and weighing approximately 24-27 g were selected and randomly assigned to a diabetes mellitus(DM)group and a zinc-treated DM(DM/Zn)group(n=6 each).In addition,12 age-matched male FVB mice weighing approximately 27-30 g were selected and randomly assigned to a non-diabetic control(Ctrl)group and a zinc-treated(Zn)group(n=6 each).Mice in the DM/Zn and Zn groups were given zinc supplementation for 3 months,with each mouse receiving 5 mg/kg of zinc sulfate by gavage every other day.Mice in the DM and Ctrl groups were given the same volume of normal saline.At the end of the experiment,the albumin-to-creatinine ratio(ACR)in urine was used as an indicator to evaluate renal function.Sirius red staining was performed to assess renal fibrosis in each group of mice.Western blotting was performed to determine the expression of fibrotic growth factors,including connective tissue growth factor(CTGF)and transforming growth factor-β1(TGF-β1),in renal tissue,and the protein expression of Nrf2,an antioxidant substance,and the protein expression levels of its downstream targets,including NAD(P)H quinone dehydrogenase 1(NQO1),heme oxygenase 1(HO-1),superoxide dismutase(SOD)-1,SOD-2,and catalase(CAT).Results 1)Compared to the Ctrl group,the urinary protein secretion levels of mice in the DM group exhibited progressive increase.After 3 months of zinc supplementation treatment,the urinary protein secretion levels of mice in the DM/Zn group decreased Compared to that of mice in the DM group,and the difference was statistically significant(P<0.05).2)Compared to that in the Ctrl group,the collagen deposition in the renal tissues of mice in the DM group increased,and the difference was statistically significant(P<0.05),while no obvious change was observed in mice in the DM/Zn group.Compared to the Ctrl group,mice in the DM group exhibited increased expression levels of CTGF and TGF-β1 in the renal tissues,but the expression levels decreased after zinc supplementation treatment,with the differences being statistically significant(P<0.05).3)Compared to that of the Ctrl group,the expression level of Nrf2 in the renal tissues of mice in the Zn and DM groups increased,and the level of Nrf2 in the renal tissues of mice in the DM/Zn group showed a further increase,with the differences being statistically significant(P<0.05).4)Compared to those of the Ctrl group,the protein expression levels of Nrf2 downstream target genes,including NQO1 and HO-1,in the renal tissues of mice in the Zn group increased,and the levels of NQO1 and HO-1 in the renal tissues of mice in the DM/Zn group showed a further increase,with the differences being statistically significant(P<0.05).Compared to those of the mice in the Ctrl group,the protein expressions of Nrf2 downstream target genes,including SOD-1,SOD-2,and CAT of in the renal tissues of the mice in the Zn group increased,while the expression levels of SOD-1,SOD-2,and CAT in the renal tissues of the mice in the DM group decreased,with the differences being statistically significant(P<0.05).Zn supplementation could completely inhibit these changes(P<0.05).Conclusions Zn supplementation has therapeutic effects on DKD and mitigates T1DM-induced renal dysfunction and oxidative injury in mice,which may be associated with the activation of the Nrf2 antioxidant signaling pathway.
2.18F-FDG PET/CT semi-quantitative parameters for predicting clinical stage Ⅰa—Ⅲa lung adenocarcinoma spreading through air spaces
Zhenzhen WANG ; Xiaotian LI ; Xingyu MU ; Yulong ZENG ; Weixia CHONG ; Jie QIN ; Zuguo LI ; Xueqin ZHAO ; Yang WU ; Cuiping XU ; Wei FU
Chinese Journal of Medical Imaging Technology 2024;40(5):735-739
Objective To observe the value of 18F-FDG PET/CT semi-quantitative parameters for predicting spread through air spaces(STAS)of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.Methods Data of 85 patients with clinical stage Ⅰa—Ⅲ a lung adenocarcinoma who underwent preoperative 18F-FDG PET/CT were retrospectively analyzed.The patients were divided into positive group(n=23)or negative group(n=62)according to whether pathology showed STAS or not.Clinical and PET/CT data were compared between groups,and logistic analysis was performed to explore the efficacy of each parameter for predicting STAS.Results Significant differences of gender,carcinoma embryonic antigen,clinical stage,pathological grade,micropapillary growth and proportion were found between groups(all P<0.05).The maximum,the mean,the peak standard uptake value(SUVmax,SUVmean,SUVpeak),as well as the maximum,the mean and the peak standard uptake value normalized by lean body mass(SULmax,SULmean,SULpeak),also the total lesion glycolysis(TLG)in positive group were all significantly higher than those in negative group(all P<0.05).Patients'gender,proportion of micropapillary growth,SUVmax and SULmax were all independent risk factors of STAS of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.The area under the curve(AUC)of the above parameters for predicting STAS was 0.666,0.912,0.839 and 0.842,respectively,and of the combination was 0.957.Conclusion 18 F-FDG PET/CT semi-quantitative parameters SUVmax and SULmax were helpful for predicting STAS of clinical stage Ⅰa—Ⅲ a lung adenocarcinoma,and further combination of gender and proportion of micropapillary growth could improve diagnostic efficacy.
3.Clinical application of abdominal belts in difficult colonoscopy
Guangqiu YU ; Jianwei ZHU ; Lin SUN ; Yudong XU ; Wen TANG ; Weixia ZHOU
Chinese Journal of Digestive Endoscopy 2024;41(6):487-491
To evaluate the effects of abdominal belts in colonoscopy for patients with low body mass index (BMI) (BMI<18.5 kg/m2) or a history of abdominal surgery, a prospective, randomized, single-blind study was conducted on colonoscopy outpatients. Patients with low BMI or a history of abdominal surgery who underwent colonoscopy at the Second Affiliated Hospital of Soochow University from January 2018 to January 2022 were enrolled. The patients were divided into the abdominal belts group and non-abdominal belts group according to whether they used abdominal belts. Differences between the two groups were compared in terms of cecal intubation time, length of colonoscope intubation into the cecum, patient repositioning, abdominal pressure, and degree of abdominal distension. A total of 296 patients (98 low BMI patients and 198 patients with a history of abdominal surgery) were enrolled, 148 in each group. The results showed that cecal intubation time (4.35±1.85 min VS 7.99±3.86 min, t=35.624, P<0.001) and length of colonoscope intubation into the cecum (72.03±10.35 cm VS 86.42±17.71 cm, t=38.442, P<0.001) were lower in the abdominal belts group, compared with those of the non-abdominal belts group. The percentage of patients requiring repositioning [18.9% (28/148) VS 71.6% (106/148), χ2=82.959, P<0.001] and abdominal pressure [6.1% (9/148) VS 52.7% (78/148), χ2=77.504, P<0.001] in the abdominal belts group were significantly lower than those in the non-abdominal belts group. There were significant differences in the degree of abdominal distension during and after colonoscopy ( P<0.001). In conclusion, the use of abdominal belts significantly improves the efficiency and effects of colonoscope intubation in difficult colonoscopy patients with low BMI and a history of abdominal surgery.
4.All-stage targeted therapy for the brain metastasis from triple-negative breast cancer.
Zimiao LUO ; Sunyi WU ; Jianfen ZHOU ; Weixia XU ; Qianzhu XU ; Linwei LU ; Cao XIE ; Yu LIU ; Weiyue LU
Acta Pharmaceutica Sinica B 2023;13(1):359-371
Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.
5. Epidemiological analysis on a family cluster of COVID-19
Yuanying QIU ; Songqiang WANG ; Xiaoli WANG ; Weixia LU ; Dan QIAO ; Jianbin LI ; Yuanyuan GU ; Yan ZENG ; Ying CHEN ; Weizhi BAI ; Bianli XU ; Tongwu HAN
Chinese Journal of Epidemiology 2020;41(4):506-509
Objective:
To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic.
Methods:
Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR.
Results:
Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020.
Conclusions
In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.
6.Clinical utility value of urinary aldosterone detection by tandem mass spectrometry in primary hyperaldosteronism screening
Wenjun MA ; Jin BIAN ; Ying LOU ; Xu YANG ; Huimin ZHANG ; Xianliang ZHOU ; Lei SONG ; Jun CAI ; Beibei ZHAO ; Ergang JIANG ; Weixia LIU ; Yating CHENG
Chinese Journal of Laboratory Medicine 2020;43(3):261-266
Objective:To explore the clinical utility of liquid chromatography tandem mass spectrometry forprimary aldosteronism screening.Methods:From January to October 2019, 413 inpatients diagnosed hypertension from Fuwai Hospital of Chinese Academy of Medical Sciences were enrolled, including 60 Primary aldosteronism(PA)patients and 353 primary hypertension patients. The plasma aldosterone concentration (PAC) and renin concentration (DRC) were measured after 2 h of standing. The 24 h urine samples were collected for measurement of aldosterone using LC-MS/MS. The performance of urine aldosterone and urine aldosterone/renin ratio (UADRR) in PA screening was evaluated by ROC, and compared with PAC/DRC ratio (ADRR). Meanwhile, the efficiency of urine aldosterone in elderly patients or patients with low blood potassium or 24 h urine sodium over 200 mmol was investigated.Results:Area under the curve (AUC)of urine aldosterone was 0.725 (95 %CI 0.679-0.767), and the best cut-off was 7.13 μg/24 h, which was lower than AUC of ADRR (0.958, 95 %CI 0.934-0.975). The AUC of UADRR was 0.947 (95 %CI 0.920-0.966), the best cut-off was 1.11 (μg/24 h)/(μIU/ml), the sensitivity and specificity were 91.7% and 89.0%, respectively. There is no significant differences found with ADRR. In patients with 24 h urine sodium over 200 mmol, AUC of aldosterone was 0.834 (95 %CI 0.730-0.910) and the best cut-off was 9.31 μg/24 h. The sensitivity and specificity were 90.9% and 68.7%, respectively. For the elderly patients over 60 years old, the AUC of urinary aldosterone was 0.860 (95 %CI 0.770-0.925), and the best cut-off was 6.91 μg/24 h. The sensitivity and specificity were 84.6% and 81.3%, respectively. When admission blood potassium was less than 3.50 mmol/L, AUC of urinary aldosterone was 0.822 (95 %CI 0.684-0.917), and the best cut-off was 10.63 μg/24 h. The sensitivity and specificity were 85.7% and 66.7%, respectively. Conclusion:The detection of aldosterone in urine by LC-MS/MS can provide clinical information for PA screening, and the screening performance is better in patients with 24-hour urine sodium over 200 mmol, elderly patients or patients with low blood potassium. If combined with renin, screening efficiency was the same as that in ADRR.
7.Effect of betulinic acid on spatial learning and memory in type 2 diabetic rats and its mechanism
Yuzhen XU ; Qian WANG ; Aihua LIU ; Weixia YANG
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(1):44-48
Objective To investigate the effects of betulinic acid on spatial learning and memory in rats with type 2 diabetes mellitus(T2DM) and to explore its underlying mechanisms.Methods Forty-five male Wistar rats were randomly divided into control group (Sham),T2DM group and betulinic acid treatment group (BA) with 15 in each group.The rats in the latter two groups were given a high fat diet plus low dose of streptozotocin (STZ) to induce T2DM,and the rats in BA group was given 10 mg/kg BA for intragastric administration once daily for 12 weeks,the rats in T2DM group and Sham group were given an equal volume of physiological saline.Morris water maze method was used to detect the cognitive function.The mRNA levels of synaptic plasticity related protein GAP-43,SYP and PSD-95 were detected by RT-PCR.The protein expressions of cholinergic neurotransmitter ChAT and Ach were detected by Elisa.Results Compared with the Sham group,the escape latency of the T2DM group was significantly prolonged on days 2-4 ((62.28 ± 2.97)s vs (47.09±2.16)s;(48.52±3.09) s vs (26.18±2.21)s;(42.31±2.80)s vs (13.42±1.23)s),the original platform quadrant time was significantly reduced ((24.60±2.42) s vs (41.85 ± 1.98) s),GAP-43,SYP,ChAT and Ach levels were significantly lower,the differences were statistically significant (the t values were 16.37,22.34,39.78,20.42,116.01,91.35,71.84,21.88 and 21.11,respectively,all P< 0.05).Compared with T2DM group,the escape latency of BA group in 2-4 days were significantly shortened ((55.61±2.75)s vs (62.28±2.97)s;(31.35±2.63)s vs (48.52±3.09)s;(42.31±2.80)s vs (16.58± 1.37) s),the original platform quadrant time increased significantly ((37.58± 2.31) s vs (24.60±2.42) s),and GAP-43,SYP,PSD-95,ChAT and Ach levels were significantly higher,and the differences were statistically significant (the t values were 6.80,16.21,33.54,14.55,41.83,35.23,36.20,12.82 and 9.97,respectively,all P<0.05).Conclusion Betulinic acid can improve the spatial learning and memory of type 2 diabetic rats,and increasing the expression of GAP-43,SYP,PSD-95,ChAT and Ach may be its potential mechanism.
8.Application status and prospect of deep vein thrombosis risk assessment tools for stroke patients
Changqing XIE ; Haifang WANG ; Lan XU ; Jianzheng CAI ; Yingying ZHANG ; Weixia YU
Chinese Journal of Modern Nursing 2019;25(35):4662-4666
? This paper reviewed the application status of the common deep vein thrombosis (DVT) risk assessment tools for stroke patients to explore the advantages and disadvantages of every tool so as to provide a basis for selecting the best assessment tools for early DVT in stroke patients.
9.The role of PCSK9 on lipid accumulation and injury in the kidney of C57BL/6 mice
Meiyan WU ; Chongsen ZANG ; Fuzhe MA ; Bin CHEN ; Weixia SUN ; Mindan SUN ; Hang YUAN ; Zhonggao XU ; Ye JIA
Chinese Journal of Nephrology 2018;34(11):845-850
Objectives To evaluate the role of PCSK9 (proprotein convertase subtilisin kexin type 9) on the lipid accumulation and kidney injury of C57BL/6 mice. Methods The 24 h urine of 12 weeks old wide type C57BL/6 mice and PCSK9 knockout (KO) mice were collected through a metabolic cage, followed by perfusion and sacrifice. Urinary microalbumin?to?creatinine ratio (UACr), total cholesterol and triglyceride in kidney tissues were measured by ELISA. BODIPY 493/503 staining and standard transmission electron microscopy (TEM) of kidney tissues was performed for evaluating lipid accumulation and podocyte foot effacement in the kidney. Kidney tissues were also evaluated by PAS stain and TUNNEL stain. PCSK9, podocin and nephrin were quantified through real?time PCR, and the Bcl?2, Bax and cleaved caspase 3 were evaluated by Western blotting. Results Total cholesterol and triglyceride contents were higher in the kidneys of PCSK9 KO mice than controls (P<0.05). The level of lipid accumulation in glomeruli and tubules through BODIPY 493/503 stain, and the amount of lipid drop in TEM were more serious in PCSK9 KO mice. UACr and podocyte foot process effacement were increased, and the transcription of podocin and nephrin were decreased in the kidneys of PCSK9 KO mice (all P<0.05). The expression of Bcl?2 was decreased, and Bax and cleavedcaspase 3 were increased in the kidney samples of PCSK9 KO mice. Conclusion PCSK9 might be reversely involved in lipid homeostasis and accumulation, resulting in injury and apoptosis in the kidneys of C57BL/6 mice.
10.Investigation and analysis of endemic fluorosis associated with drinking water in Jiaozuo City of Henan Province in 2016
Xiaoli XU ; Jingxuan XU ; Tangyun LI ; Weixia RAN
Chinese Journal of Endemiology 2017;36(12):895-898
Objective To fully grasp the epidemic situation of drinking water type of endemic fluorosis in Jiaozuo City of Henan Province,evaluate the efficacy of the prevention and control measures,and to provide a basis for prevention and control of the disease.Methods According to "The Measures for Control and Elimination of Key Endemic Diseases",all the diseased villages in Jiaozuo City were investigated.For all diseased villages in accordance with the improved water or no improved water,drinking water samples were collected,the fluorine content in water samples was determined based on the standard testing method for drinking water (GB/T 5750.5-2006);all children aged 8 to 12 years old of the surveyed villages were examined and determined dental fluorosis using "Diagnostic of Dental Fluorosis" (WS/T 208-2011);all evaluations were based on the criteria for drinking water-based fluorosis control (National Health Control [2014] No.79).Results Totally 7 counties (cities) 59 townships 589 diseased villages were surveyed in the city,586 diseased villages had improved the water quality,the rate was 99.49%,the number of villages that used the water facility normally was 571,the normal utilization rate was 97.44%,and there were 15 villages with excessive fluoride in water.A total of 35 057 children aged 8 to 12 years old in the diseased villages of the city were examined and 13 846 cases were detected dental fluorosis,the detection rate of dental fluorosis was 39.50%,the index of dental fluorosis was 0.65,which was a moderate epidemic;147 villages reached the control of standard among the 586 diseased villages with improved water,and the compliance rate was 25.09%,and the 7 drinking water type local fluoride poisoning epidemic counties (cities) in the area all did not reached the control standards.Conclusion Totally 439 diseased villages in the city have not meet the control standard,we should strengthen the monitoring,implement measures to improve water quality,strengthen the management and maintenance of water projects to ensure that the disease affected population to have qualified drinking water in a long-term,and gradually achieve the target to control and eliminate city's drinking water type of endemic fluorosis.

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