1.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
2.Independent risk factors related to unintended initial dissection of the poste-rior plane in small incision lenticule extraction performed by surgeons with different qualifications
Zeyu ZHU ; Qing WANG ; Jian XIONG ; Nanye WANG ; Jingjing XU ; Kang YU ; Zheliang GUO ; Yicheng XU ; Yifeng YU
Recent Advances in Ophthalmology 2024;44(7):540-543
Objective To investigate independent risk factors for unintended initial dissection of the posterior plane(UIDPP)during small incision lenticule extraction(SMILE)by surgeons with different qualifications.Methods A total of 1 600 patients(3 003 eyes)who underwent SMILE performed by three surgeons with different qualifications from April to September 2021 were selected as the research subjects,including 911 males and 689 females,with an average age of(21.82±3.55)years.The incidence of UIDPP in patients was recorded,along with a comprehensive summary of the age,gender,eyes,surgeons,surgical proficiency,subjective refraction,central corneal thickness,lenticule thickness,side cut angle,and peripheral lenticule thickness of the patients.Independent risk factors of UIDPP were analyzed using the binary logistic regression.Test level:α=0.05.Results In this study,the incidence of UIDPP was 6.56%(197/3 003),and the lenticule was successfully removed in all eyes.Multivariate logistic regression analysis demonstrated that surgeon(P=0.035),surgical proficiency(P=0.026),eyes(P=0.007),lenticule thickness(P<0.001),and peripheral lenticule thick-ness(P<0.001)were independent risk factors associated with the UIDPP during SMILE surgery.No significant differences were observed in other parameters(all P>0.05).Conclusion Surgeons,surgical proficiency,eyes,lenticule thick-ness,and peripheral lenticule thickness are independent risk factors of UIDPP.
3.Analysis on Children's Health Equity in Countries along the"Belt and Road"Based on Concentration Index and Thiel Index
Linhong LI ; Zeyu TAN ; Xinyi ZHANG ; Zixuan WEN ; Tongtong GUO ; Zewen XU ; Qi JING ; Wengui ZHENG
Chinese Health Economics 2024;43(2):49-52
Objective:To analyze and evaluate the equity of children's health in countries along the"the Belt and Road",promote further attention to children's health in countries along the route,and promote cooperation and exchanges on children's health between China and countries along the"the Belt and Road".Methods:Using concentration index and concentration curve to measure overall equity,and using the Thiel index for intraregional and interregional euqity measurement.Results:The under-five mortality concentration index is 0.349 7,the concentration curve is below the absolute fair line.The Thiel index shows that inequality in low-income countries,lower-middle-income countries,upper-middle-income countries and high-income countries is the leading cause of child health inequities in the"the Belt and Road"countries.Conclusion:There is inequity in the health of children in countries along"the Belt and Road Initiative",countries along the"the Belt and Road"should take comprehensive measures to reduce the under-five mortality rate,at the same time strengthen international cooperation to further promote equity in children's health in"Belt and Road"countries.
4.Researches on multi-level rehabilitation service system in China:a bibliometrics analysis
Ruixue YE ; Yulong WANG ; Yan GAO ; Kaiwen XUE ; Zeyu ZHANG ; Jie YAN ; Yucong ZOU ; Guo DAN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(6):630-638
Objective To analyze the trends,cooperation,topics and hotspots of researches about multi-level rehabilitation service system in China. Methods The literature on multi-level rehabilitation service system in China was searched and screened in databases of CNKI from 1983 to 2023.The number of the articles was described,and the cooperation,research hotspots and changing trend were analyzed using VOSviewer. Results A total of 4 643 articles were included.The number of the articles tended to increase and developed in stages.Nine groups with five or more researchers were found,and seven of them cooperated with each other.The most frequent keywords were community-based rehabilitation(occurrence 1 251 with connection strength 1 780),stroke(occurrence 674 with connection strength 1 126),family rehabilitation(occurrence 412 with connection strength 514),rehabilitation nursing(occurrence 178 with connection strength 240)and quality of life(occur-rence 156 with connection strength 311).The researchers initially focused on disability rehabilitation,then fo-cused on community-based rehabilitation and family rehabilitation,and gradually focused on the quality of life,activities of daily living,satisfaction,mental health,negative emotion and healthcare consortium in recent years. Conclusion The researches about multi-level rehabilitation service system are developing in China,focusing on commu-nity-based rehabilitation,stroke,family rehabilitation,rehabilitation nursing and quality of life.The cooperation among scholar groups need to be strengthened.Quality of life,activities of daily living,satisfaction,mental health,negative emotion and healthcare consortium may be the hotspots in the future.
5.Sestrin1 is involved in the regulation of gluconeogenesis in mouse liver cells
Yanfang GUO ; Chao GENG ; Xianghong XIE ; Enhui CHEN ; Zeyu GUO ; Minglong ZHANG ; Xiaojun LIU
Basic & Clinical Medicine 2024;44(2):141-146
Objective To investigate the role and regulatory mechanism of stress-inducing protein 1(SESN1)in liver gluconeogenesis of fasting mice.Methods RT-qPCR was used to detect mRNA expression of SESN1 in liver tissues of C57BL/6J mice and primary mouse hepatocytes treated with forskolin(Fsk)and dexamethasone(Dex).HepG2 cells were transfected with plasmids and the effects of SESN1 overexpression on mRNA expression of gluconeogenesis related genes PGC-1α,PEPCK and G6Pase was detected by RT-qPCR.The effect of SESN1 on the promoter activity of PGC-1α in HepG2 cells was studied using a dual luciferase reporter system.The effect of SESN1 on PGC-1α deacetylation was detected by overexpression of SESN1 and inhibition of SIRT1 expression.By knocking down SIRT1 expression,we detected whether it mediated the changes in mRNA levels of SESN1 in-duced gluconeogenesis related genes.Results The mRNA expression of SESN1 was significantly increased in liver tissues of starved C57BL/6J mice and in primary hepatocytes treated with Fsk and Dex(P<0.001).Over-expression of SESN1 in HepG2 cells promoted mRNA expression of PGC-1α,PEPCK and G6Pase(P<0.001)and promoter activity of PGC-1α(P<0.001).Over-expression of SESN1 decreased the acetylation level of PGC-1α in primary hepatocytes.Sirt family inhibitors NAM and shRNA adenovirus interfered with SIRT1 expression respective-ly,and antagonized the deacetylation effect of SESN1 on PGC-1α.The expression of PGC-1α,PEPCK and G6Pase induced by SIRT1 was also significantly impaired(P<0.000 1).Conclusions SESN1 regulates liver gluconeogene-sis in mice with a SIRT1-dependent mechanism.
6.Application value of artificial neural network in laparoscopic surgery training
Yitai GUO ; Zeyu LIU ; Yanjiao OU ; Yong DENG ; Hong WANG ; Peng HU ; Leida ZHANG
Chinese Journal of Digestive Surgery 2020;19(6):660-665
Objective:To investigate the application value of artificial neural network in laparoscopic surgery training.Methods:The prospective cohort study was conducted. A total of 158 trainees from the First Hospital Affiliated to Army Medical University between Semptember and November, 2019 who had no experience in laparoscopic technology were selected for laparoscopic surgery training, including 52 graduate students of surgery from grade 2019, 2018 and 2017, 58 surgeons receiving standardized residency training, 12 interns and 36 refresher physicians. The 158 trainees were divided into two groups using the random number table. Trainees trained by artificial neural network laparoscopic simulator were allocated into artificial neural network group, and trainees trained by box laparoscopic simulator were allocated into general laparoscopic simulator group. Trainees in both groups were trained using the laparoscopic simulator for 10 hours (5-day continuous training, 2 hours per day) on fundamentals of laparoscopic surgery. Observation indicators: (1) comparison of operation grades on laparoscopic simulator before and after training in the two groups; (2) comparison of improvement of the operation grades on laparoscopic simulator after training between the two groups. Measurement data with normal distribution were represented as Mean± SD, comparison within groups was analyzed using the paired t test and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M (range). Results:A total of 158 trainees were selected for eligibility, including 140 males and 18 females, aged from 23 to 34 years, with a median age of 27 years. Of the 158 trainees, 79 were in the artificial neural network group and 79 were in the general laparoscopic simulator group. (1) Comparison of operation grades on laparoscopic simulator before and after training in the two groups: operation grades of the nails transferring, pattern cutting, ligation, sewing knots in vivo and sewing knots in vitro for the artificial neural network group before training were 51.2±4.9, 45.6±3.7, 43.0±3.6, 42.1±3.1, and 39.6±3.1, respectively. The above indicators for the artificial neural network group after training were 78.6±3.0, 76.4±3.9, 79.9±2.5, 78.3±3.5, and 84.1±3.8, respectively. There were significant differences in the above indicators for the artificial neural network group before and after training ( t=-42.490, -56.256, -80.373, -70.802, -79.742, P<0.05). The above indicators for the general laparoscopic simulator group before training were 50.1±2.9, 45.4±3.9, 42.7±3.0, 42.3±3.4, and 39.2±4.7, respectively. The above indicators for the general laparoscopic simulator group after training were 70.4±5.0, 69.8±4.0, 72.3±3.3, 72.3±3.5, and 72.8±3.2, respectively. There were significant differences in the above indicators for the general laparoscopic simulator group before and after training ( t=-28.942, -42.436, -58.357, -52.322, -53.098, P<0.05). (2) Comparison of improvement of the operation grades on laparoscopic simulator after training between the two groups: improvement of the operation grades in the nails transferring, pattern cutting, ligation, sewing knots in vivo and sewing knots in vitro for the artificial neural network group after training were 27.4±5.7, 30.8±5.0, 36.9±4.1, 36.2±4.5 and 39.5±5.4, respectively. The above indicators for the general laparoscopic simulator group after training were 20.3±6.2, 24.4±5.1, 29.6±4.5, 29.9±5.1 and 33.5±5.6, respectively. There were significant differences in the above indicators between the two groups ( t=7.597, 7.946, 10.638, 8.200, 6.969, P<0.05). Conclusion:The introduction of artificial neural network in laparoscopic surgery training can improve the training effects.
7.Expression of FOXD1 in glioma tissues and its correlation with prognosis of patients
JIANG Zeyu ; LU Weicheng ; GUO Zongze ; CHENG Peng
Chinese Journal of Cancer Biotherapy 2018;25(4):351-356
[Abstract] Objective: To evaluate the expression level of FOXD1 in glioma tissues of different grades, and to investigate the correlation between the expression of FOXD1 and the prognosis of glioma patients. Methods: The tumor tissues were collected from 40 glioma patients, who received surgical treatment in the neurosurgery department of the First Hospital of China Medical University from September 2014 to February 2015; Seven non-tumor tissues obtained from patients underwent internal decompression for traumatic brain injury were used as controls. The FOXD1 expression in glioma and non-tumor brain tissues was analyzed by qRT-PCR and IHC, and the correlations between clinical pathological features of glioma patients and FOXD1 expression level were analyzed. Furthermore, the Kaplan-Meier method was used to analyze the relationship between FOXD1 expression and survival time of patients. In addition, the expression of FOXD1 in glioma tissues and its relationship with patients’prognosis were confirmed by the data from GEO (GSE4290, GSE2223) and Rembrandt database. Results: qRT-PCR showed that the FOXD1 mRNA expression in glioma tissues of WHO grade IV was significantly higher than that of non-tumor brain tissues and glioma tissues of WHO grade II (P<0.01). German immunohistochemical score (GIS) was used to evaluate the immunohistochemical staining intensity, and the relationship between FOXD1 expression and clinical pathological features was analyzed. The results showed that FOXD1 in glioma tissues was related to WHO phathological grade level (χ2=11.73, P<0.01). There was statistically significant difference between the survival time of FOXD1 high expression group and FOXD1 low expression group (P=0.043). The data from GEO data base (GSE4290, GSE2223) and Rembrandt datasets showed that glioma tissues have a higher FOXD1 mRNA expression level than normal brain tissues, and the elevated expression of FOXD1 mRNA was negatively associated with the survival time of glioma patients. Conclusion: FOXD1 was highly expressed in glioma tissues, and the expression level of FOXD1 was increased as the pathological grade increases. The elevated expression of FOXD1 was related with the poor survival of glioma patients.
9.Relationship between Uric Acid Levels in Patients with Acute Ischemic Stroke and Discharged Outcome
Yumei GUO ; Long MA ; Chengyue BAO ; Zeyu HUANG ; Fangrui LI ; Lirong YANG ; Wenting BAI ; Hui CHENG ; Wenbo LIU ; Liying LU ; Weijun TONG ; Mo ZHOU ; Hongmei LI ; Tan XU
Journal of Modern Laboratory Medicine 2015;(3):17-20
Objective To examine the association between uric acid (UA)levels of patients with acute ischemic stroke at ad-mission and discharged outcome.Methods The acute ischemic stroke patients of Xinganmeng People’s Hospital in Inner Mongolia,from June 1,2009 to May 31,2012 were continuity included in the present study,the included analysis sample size were 3 440 cases.Poor discharged outcome was defined as the occurrence of disability or death.With reference to the Modi-fied Rankin's Scale (MRs)Stroke Scale,Scores were recorded in the questionnaires,score of 3 or more (MRs≥3)was de-fined as disability.The patients were all grouped by P20,P60,P90 of UA,binary logistic regression were used in studying of risk factors,calculated the odds ratios (Odds ratio,OR)and 95% confidence interval (95% Confident interval,95%CI).All tests were two-sided test and a significance level of 0.05.Results A total of 359 people occurred poor outcomes in the stud-y,accounting for 10.44%.Univariate logistic regression analysis of poor outcome occurred showed that relative to the lowest group(P20,UA≤222.6 mmol/L),the second and third group (UA:222.7 ~ 310.9 mmol/L and 311.0~419.7 mmol/L) OR (95% CI)were:0.70(0.53~0.91)(P <0.05)and 0.66(0.49~0.88)(P <0.05).After adjusted age,body tempera-ture,high blood pressure,hyperglycemia,history of stroke,high triglycerides,high LDL-C and smoking,relative to the low-est level group,the second and third group occurred poor outcoming OR (95% CI)were:0.70(0.53~0.93)(P <0.05)and 0.66(0.48~0.90)(P <0.05).Conclusion Higher levels of uric acid levels in patients with acute ischemic stroke may inde-pendently related with occurred poor discharged outcome.
10.Influence of recurrence on outcome of acute ischemic stroke
Fangrui LI ; Chengyue BAO ; Zeyu HUANG ; Yumei GUO ; Lirong YANG ; Wenting BAI ; Liying LYU
Clinical Medicine of China 2015;31(10):910-914
Objective To explore the adverse effects of recurrence of acute ischemic stroke at discharge.Methods Continuously including 3 440 acute ischemic stroke patients from June 1,2009 to May 31, 2012 in Department of Neurology of the People's Hospital of Xinganmeng of Inner Mongoha Autonomous Region were esearch objects.Poor outcome was defined as the occurrence of disability or death at discharge.Disability was defined as the Modified Rankin ' s Scale (MRs), when MRs was 3 or more.Binary logistic regression was used to analysis the risk factors ,calculated the odds ratios(OR) and 95% confidence interval (95%CI).Results A total of 359 (10.44%) patients occurred poor outcomes, of whom 136 (37.88%) patients occurred the recurrence of ischemic stroke.Multiple logistic regression analysis showed that age (OR=1.24,95%CI 1.09-1.41), body temperature (OR =1.92,95 % CI 1.43-2.57), hypertension (OR =1.73,95 % CI 1.33-2.24), high blood sugar (OR=1.67,95%CI 1.26-2.20) ,glycerin trilaurate(OR=0.41,95%CI0.27-0.62) ,smoking (OR =1.37,95%CI 1.01-1.85) and recmrrence(OR=1.49,95%CI 1.15-1.95) were independent risk factors of poor outcome at discharge.The recurrence of acute ischemic stroke can increase the risk of the occurrence of poor outcome at discharge up to 49%.Conclusion Recurrence is an independent risk factor for the poor outcome of acute ischemic stroke, we should focus on secondary prevention of stroke patients at the clinical work and health education to reduce the recurrence of ischemic stroke.


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