1.Inhibitory Effects of the Slit Guidance Ligand 1-3’ Untranslated Region on the Fibrotic Phenotype of Cardiac Fibroblasts
Ya WANG ; Huayan WU ; Yuan GAO ; Rushi WU ; Peiying GUAN ; Hui LI ; Juntao FANG ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):466-474
ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region (3’UTR) of slit guidance ligand 1 (Slit1) (Slit1-3’UTR) on the fibrotic phenotypes of cardiac fibroblasts (CFs) and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs (mCFs). The expression of fibrosis-related genes in mCFs, such as collagen type 1 alpha1(COL1A1), collagen type 3 alpha3 (COL3A1) and alpha smooth muscle actin (α-SMA) were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ (Ang Ⅱ) was used to treat mCFs, and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt, miR-34a-5p mimic was transfected into mCFs, followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt, and the levels of miR-34a-5p and its target gene SIRT1(si-SIRT1) in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes, proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs, while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes, and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.
2.Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects
Liu FEN ; Zhu BOFENG ; An YING ; Zhou ZHIFEI ; Xiong PEIYING ; Li XUAN ; Mi YANG ; He TONGQIANG ; Chen FAMING ; Wu BULING
International Journal of Oral Science 2024;16(3):539-552
Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR-insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.
3.Clinical effects of probiotics combined with bismuth quadruple therapy for Helicobacter pylori infected patients
Min GUI ; Qiuyun GU ; Yusen HU ; Chenyuan YAN ; Ying SHAO ; Lina XIA ; Jieyi HE ; Peiying WU ; Yiming HONG ; Qiuju DU
Shanghai Journal of Preventive Medicine 2024;36(5):482-487
ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy (BQT) on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori (HP) positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT, followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT, followed by 4 weeks of oral probiotic placebo. 13C urea breath test was used to evaluate the clinical efficacy, gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention, and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups (P>0.05). Before the intervention, there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention, patients in the probiotic group had significantly lower pain scores on acid reflux (1.10±0.30 vs 1.35±0.53, P<0.05) and stomach or abdominal hunger than in the placebo group (1.07±0.26 vs 1.30±0.52, P<0.05). Through the before-and-after comparison of the probiotic group, the scores of abdominal pain (1.24±0.44 vs 1.58±0.71, P<0.05), stomach or abdominal hunger (1.07±0.26 vs 1.27±0.45, P<0.05) and dry and hard stool (1.24±0.49 vs 1.48±0.75,P<0.05) were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy, but it does not improve the eradication rate of HP.
4.Acupuncture plus naloxone hydrochloride in the treatment of coma after surgery for cerebralhemorrhage: a randomized controlled trial
Min CHEN ; Shuangshuang WU ; Peiying TANG
Journal of Acupuncture and Tuina Science 2022;20(2):134-138
Objective: To observe the efficacy of acupuncture combined with naloxone hydrochloride in the treatment of coma after surgery for cerebral hemorrhage and to explore its possible mechanism of action. Methods: Seventy-two patients were divided into a control group and an observation group according to the random number table method, with 36 cases in each group. The control group was treated with intravenous naloxone hydrochloride, and the observation group received additional acupuncture treatment. After 1 month of treatment, the awakening rate, Glasgow coma scale (GCS) score, cerebral edema volume, mean velocity (Vm) of the middle cerebral artery, and cerebrospinal fluid Caspase-3, and macrophage migration inhibitory factor (MIF) levels were compared between the two groups. Results: During the study, there were 2 cases of shedding in the control group and 34 remaining valid cases; 1 case of shedding in the observation group and 35 remaining valid cases. After treatment, the awakening rate was higher in the observation group than in the control group (P<0.05); the GCS score increased in both groups compared with that before treatment (P<0.05), and was higher in the observation group than in the control group (P<0.05); the volume of cerebral edema decreased in both groups (P<0.05), and was smaller in the observation group than in the control group (P<0.05); the middle cerebral artery Vm increased in both groups (P<0.05), and was higher in the observation group than in the control group (P<0.05); the cerebrospinal fluid Caspase-3 and MIF levels decreased significantly in both groups (P<0.05) and were lower in the observation group than in the control group (P<0.05). Conclusion: Acupuncture combined with naloxone hydrochloride for the treatment of coma after surgery for cerebral hemorrhage can promote patients' awakening, improve the degree of coma, reduce the volume of cerebral edema, and enhance cerebral blood flow velocity, producing a better effect than naloxone hydrochloride used alone; it may be related to its reduction of cerebrospinal fluid Caspase-3 and MIF levels.
5.Multivariate analysis of CT signs of ipsilateral central lymph node metastasis in single papillary thyroid carcinoma
Lijiang WU ; Yanyan SHU ; Zhijiang HAN ; Peiying WEI ; Xufeng LAI
Chinese Journal of Endocrine Surgery 2019;13(4):305-308
Objective To investigate the diagnostic value of CT signs of ipsilateral central lymph node metastasis (ICLNM) in single papillary thyroid carcinoma (PTC) by multivariate regression analysis.Methods The CT data of 302 single PTC with diameter >1.0 cm confirmed by operation and pathology were retrospectively analyzed.The optimal thresholds of lymph node metastasis diameter were obtained by receiver operating characteristic (ROC) curve analysis.And multivariate regression analysis was used to analyze the relation between lymph node size,degree of enhancement,calcification or cystic degeneration,central turbidity,positive lateral cervical lymph nodes and the ICLNM positivity.Results In 302 PTC,the proportion of ICLNM positive and negative was 63.6% (192/302) and 36.4% (110/302),respectively.According to the ROC curve,with the increase of lymph node diameter,the sensitivity of diagnosing lymph node metastasis decreased and the specificity increased.When the threshold was 0.4 cm,Youden index was the largest (0.358),and the sensitivity and specificity was 50.5% and 80.3%,respectively.Multivariate analysis showed that the diameter≥0.4 cm,high enhancement,central turbidity and lateral cervical lymph nodes positivity were the independent risk factors of ICLNM,and the OR values were 4.189[95% CI (2.037-8.617)],3.875 [(95% CI (1.561-9.617)],4.054[(95%CI (2.230-7.371)] and 8.735 [(95% CI (1.093-69.831)],respectively.Calcification or cystic degeneration was not statistically significant in ICLNM.Conclusions The diameter ≥0.4 cm,high enhancement,central turbidity and lateral cervical lymph nodes positivity are the independent risk factors of ICLNM.Although calcification or cystic degeneration is not the independent risk factor,it has high accuracy for ICLNM positivity.The accurate identification of these signs can help surgeons to take a more thorough surgical treatment and has great significance to reduce postoperative recurrence.
6.The diagnostic significance of CT value in thyroid benign solitary coarse calcification nodules
Peiying WEI ; Lexing ZHANG ; Zhijiang HAN ; Ying WU ; Jinwang DING
Chinese Journal of Endocrine Surgery 2018;12(1):43-46
Objective To investigate the diagnostic significance of CT in thyroid benign solitary coarse calcification nodules (BCCN).Methods A total of 56 BCCN confirmed by surgical pathology in 55 patients were evaluated,and they were compared with 33 papillary thyroid carcinoma (PTC) in 32 patients.The distribution differences of the average CT values and the maximum CT values in BCCN and PTC were observed.The optimal thresholds of the average CT values and the maximum CT values in BCCN and PTC were established by re ceiver operating characteristic(ROC) curve analysis.Results The average CT values in BCCN and PTC were significantly different (t=4.992,P=0.000).The ROC area under curve (AUC) was 0.757 (95% confidence interval 0.0657-0.0857).When the critical value was 743.4 Hu,Youden index was the largest and the sensitivity and specificity was 48.2% and 93.9%,respectively.When the critical value was 891.1 Hu,the sensitivity and specificity was 21.4% and 100%,respectively.The maximum CT values in BCCN and PTC were significantly different (t=5.029,P=0.000).The ROC AUC was 0.775 (95% confidence interval 0.0681-0.0869).When the critical value was 1201.5 Hu,Youden index was the largest and the sensitivity and specificity was 51.7% and 91.0%,respectively.When the critical value was 1373.5 Hu,the sensitivity and specificity was 42.9% and 100%,respectively.Conclusions CT value is of great significance to the diagnosis of BCCN and has high specificity.Compared with the average CT value,the maximum CT value has a relatively higher sensitivity,providing an important base for reducing unnecessary surgical trauma.
7.Quality Standard of Huangqi Baoxin Mixture
Wei WU ; Peiying ZHANG ; Yonggang CHEN ; Xingjie CHANG ; Shiqiang WU ; Jiayu ZHANG
Herald of Medicine 2018;37(3):341-344
Objective To establish a quality standard of huangqi baoxin mixture and improve its quality control system. Methods The qualitative analysis of Astragalus membranaceus,Salvia miltiorrhiza,Forsythia,and Angelica were performed by TLC.The content determination of astragalosideⅣin the huangqi baoxin mixture was conducted by HPLC-ELSD. Results As-tragalus membranaceus,Salvia miltiorrhiza,Forsythia,and Angelica in the huangqi baoxin mixture could be accurately identified by TLC.The linear range of astragaloside Ⅳ was 1.224-10.20 μg (r=0.999 5).RSDs of precision,stability,and reproducibility tests were lower than 3.0%;the recovery was 96.2%-102.9% with RSD at 2.20% (n=6). Conclusion The established quan-titative method is simple,accurate,and reliable with high specificity which can be used to control the quality of huangqi baoxin mixture.
8.Education via WeChat improves glucose control and pregnant outcomes in women with gestational diabetes mellitus
Ying SHAO ; Gengsheng HE ; Xianming XU ; Jieyi HE ; Peiying WU
Chinese Journal of Perinatal Medicine 2018;21(10):678-682
Objective To evaluate the effect of strengthening nutrition intervention in gravidas with gestational diabetes mellitus (GDM) with WeChat on blood glucose control and pregnant outcomes.Methods A total of 410 gravidas,diagnosed with GDM and treated in the Department of Clinical Nutrition of Shanghai General Hospital from October 2015 to April 2016,were enrolled and randomly divided into two groups (n=205).The control group received traditional nutrition clinic education only,while the intervention group was given strengthened nutrition education through WeChat in addition to traditional education.Blood glucose level and insulin dosage were followed up after one,two and four weeks of intervention.Pregnant outcomes and patient satisfaction were investigated on 42 d after delivery.T test,Chi-square test and non-parametric test were used for statistical analysis.Results (1) Two weeks after the intervention,the average 1-hour postprandial blood glucose in the intervention group was lower than in the control group [(7.46± 1.01) vs (7.68± 1.06) mmol/L,t=2.243,P=0.025].After 4 weeks,both 1-and 2-hour postprandial blood glucose levels of the intervention group were lower than those of the control group [(7.03±0.65) vs (7.33±0.63) mmol/L,t=4.629,P<0.05;(6.00±0.65) vs (6.21 ±0.62) mmol/L,t=3.153,P<0.05] and more gravidas achieved euglycemia [79.9% (151/189) vs 60.8% (113/186),x2=16.483,P<0.001].(2) Compared with the control group,the intervention group had a higher vaginal delivery rate [38.7% (72/186) vs 50.5% (95/188),x2=5.288,P=0.021] and a lower rate of postpartum complications [9.1% (17/186) vs 2.1% (4/188),x2=7.394,P=0.007].All of the gravidas in the intervention group were satisfied with the WeChat intervention except one lost to follow up [99.5% (203/204)].Conclusions Strengthening nutrition education through WeChat is much more effective than traditional nutritional outpatient education alone in order to achieve a better control of blood glucose and improve pregnant outcomes in GDM women.This intervention is highly acceptable to gravidas and can be further extensively applied in nutrition clinic.
9.Efficacy and safety of nonablative radiofrequency in facial rejuvenation
Jie YAN ; Guoxuan WU ; Ge ZHANG ; Peiying ZHANG
Journal of Regional Anatomy and Operative Surgery 2017;26(5):366-369
Objective To evaluate the efficacy and safety of nonablative radiofrequency in facial rejuvenation.Methods A total of 198 patients with facial skin relaxing or wrinkles in the 153rd Central Hospital of PLA from July 2010 to March 2015 were treated with nonablative radiofrequency,of which 42 cases were male,156 cases were female,the ages were from 30 to 60 years old,Fitzpatrick skin type was Ⅲ~Ⅳ.The nonablative radiofrequency were performed in all the patients.Output:Monopolar RF 90~110W,Bipolar RF 40~45W,Periorbital RF 40~50W.The total course of treatment had 6 times with a fixed 10-day interval after each therapy.Results In 198 facial skin aging patients,the total effective rate was more than 90%,the half-year effective maintenance rate was more than 70%.Complications included slight oedema and mild erythema that were minor and transitory.Side effects such as post-inflammatory hyperpigmentation,epidermal burns and scar formation were not observed.Conclusion The nonablative radiofrequency is safe and effect on facial rejuvenation with less complications.
10.Differential diagnostic value of CT scan minimum attenuation values in adrenal adenomas and non-adenomas
Ying WU ; Miaoping ZHU ; Zhiiiang HAN ; Peiying WEI ; Zhikai LEI
Chinese Journal of Endocrine Surgery 2017;11(3):192-197
Objective To investigate the differential diagnostic value of CT scan minimum attenuation values (minAVsCT) in adrenal adenomas and non-adenomas.Methods CT scan data of 89 cases of clinical and pathologically confirmed adrenal adenomas were subjected to retrospective analysis and compared with data of 46 cases involving 50 non-adenomas (25 metastases,20 pheochromocytomas,3 lymphomas,and 2 cortical carcinomas).The distributions of mean attenuation values (meanAVs) ¥ 10 Hu and minAVs ¥0 Hu and CT histogram analysis with ≥ 10% negative pixels were observed in adrenal adenomas and non-adenomas,and the diagnostic sensitivity and specificity of these 3 methods for adenomas were calculated.Results The distributions of unenhanced meanAVs ¥ 10 Hu,minAVs ¥0 Hu,and CT histogram analysis with ≥ 10% negative pixels among cases of adenoma and non-adenoma were 62.9% (56/89) and 0% (0/50) (x2=52.687,P=0.000),84.3% (75/89) and 2% (1/50) (x2=83.917,P=0.000),and 77.5% (69/89) and 0% (0/50) (x2=83.917,P=0.000),respectively.The respective diagnostic sensitivities,specificities,false negative rate (FNR),false positive rate (FPR),positive pre dictive value (PPV),negative predictive value (NPV) and accuracy of these 3 methods for adenomas were 62.9%vs 84.3% vs 77.5%,100% vs 98.0% vs 100%,37.1% vs 15.7% vs 22.5%,0 vs 2% vs 0,100% vs 98.7% vs 100%,60.2% vs 77.8% vs 71.4%,and 76.3% vs 89.2% vs 85.6%.Conclusion Although the specificity and PPV of minAVs≤0Hu is slightly less than meanAVs≤10Hu and CT histogram analysis with ≥ 10% negative pixels,it exhibits the best sensitivity and accuracy with a simple operation,and is thus suitable for clinical application.

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