1.EGCG Promotes Aβ Clearance of Microglia Through Blockage of the HDAC6-PI3K/AKT/mTOR Signalling Axis Followed by Autophagy Activation
Yu LIN ; Kaiwen HUANG ; Honghai HONG ; Dan ZHU ; Yousheng MO ; Dongli LI ; Shuhuan FANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):486-497
ObjectiveTo clarify whether epigallocatechin gallate (EGCG) is involved in the clearance of amyloid β-protein (Aβ) and autophagy induction by microglia, so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease (AD). MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups, with some additional wild type (WT) mice as the control group, each group consisting of 15 mice. The EGCG group received continuous gavage administration[5 mg/(kg·d)] for 8 weeks, followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein (Aβ)in the brain parenchyma of the mice, and immunofluorescence was employed to detect the expression levels of Aβ1-42, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the hippocampal tissue of the mice. Additionally, N9 mouse microglial cells were induced with 20 µmol/L Aβ1-42, and the cell viability was measured after treatment with different concentrations of EGCG (5 µmol/L, 10 µmol/L, 20 µmol/L). Western blotting was used to detect the levels of Aβ1-42, low density lipoprotein receptor-related protein 1(LRP1), receptor for advanced glycation endproducts (RAGE), amyloid precursor protein (APP), insulin degrading enzyme (IDE), neprilysin (NEP), microtubule associated protein 1 hydrogen chain 3(LC3)-Ⅱ/LC3-Ⅰ, phosphatidylinositol 3-hydroxy kinase(PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and histone deacetylase 6(HDAC6). Finally, through the co-culture of microglial cells and neuronal SH-SY5Y cells, cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field (P<0.05), and enhanced the percentage of alternation in the Y-maze test (P<0.01); EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia; in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells (P<0.01), upregulated RAGE activity (P<0.05), and promoted the internalization and phagocytosis of Aβ (P<0.01). ECGC activated microglial autophagy by downregulating the level of HDAC6 (P<0.05), inhibiting the phosphorylation of PI3K, AKT, mTOR (P<0.001), and increasing the LC3-Ⅱ/LC3-I ratio (P<0.001); EGCG improved the survival rate of SH-SY5Y cells (P<0.05) and reduced the activity of Caspase-3 (P<0.01) by clearing Aβ1-42 through microglia, and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.
2.Efficacy of NT-proBNP,hs-CRP,D-D,and PCT in predicting heart failure after acute myocardial infarction based on ROC and DCA curve analysis
Yutao LI ; Honghai CUI ; Bingguang CHEN
International Journal of Laboratory Medicine 2024;45(6):686-691,697
Objective To investigate the predictive efficacy of serum aminoterminal brain natriuretic pep-tide precursor(NT-proBNP),hypersensitive C-reactive protein(hs-CRP),D-dimer(D-D)and procalcitonin(PCT)in heart failure after acute myocardial infarction(AMI),Methods A total of 100 AMI patients admit-ted to the hospital from July 2021 to July 2023 were enrolled in the study as the observation group,In addi-tion,100 healthy people who underwent physical examination in the hospital during the same period were en-rolled as the control group,The serum levels of NT-proBNP,hs-CRP,D-D and PCT were detected and com-pared between the observation group and the control group,The AMI patients enrolled in the study were fur-ther divided into the heart failure group(31 cases)and the non-heart failure group(69 cases)according to the presence or absence of heart failure.The serum levels of NT-proBNP,hs-CRP,D-D,and PCT were compared between the two groups,Univariate analysis and multivariate Logistic regression analysis were used to analyze the risk factors of heart failure after AMI,Receiver operating characteristic(ROC)curve and decision curve a-nalysis(DCA)were used to analyze the predictive efficacy of serum NT-proBNP,hs-CRP,D-D and PCT for heart failure after AMI.Results The levels of serum NT-proBNP,hs-CRP,D-D and PCT in the observation group were higher than those in the control group(P<0.05).The serum levels of NT-proBNP,hs-CRP,D-D and PCT in the complicated heart failure group were higher than those in the non-heart failure group(P<0.05),Body mass index(BMI),smoking history,hypertension,number of diseased vessels,serum uric acid(SUA),low-density lipoprotein cholesterol(LDL-C),NT-proBNP,hs-CRP,D-D and PCT were risk factors for heart failure after AMI(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of combined detection of serum NT-proBNP,hs-CRP,D-D and PCT for predicting heart failure after AMI was 0.857(95%CI:0.811-0.948),the sensitivity was 96.12%,and the specificity was 91.28%,which were higher than the corresponding efficacy indexes of single detection(P<0.05).DCA analysis showed that when the high-risk threshold was 0-0.99,the net benefit rate was greater than 0,which had clinical significance,When the threshold was 0-0.76,the net benefit rate of combined detection of serum NT-proBNP,hs-CRP,D-D and PCT was better than that of serum NT-proBNP,hs-CRP,D-D and PCT alone.Conclusion Combined detection of serum NT-proBNP,hs-CRP,D-D and PCT can improve the predictive efficiency of AMI compli-cated with heart failure,BMI,smoking history,hypertension,number of diseased vessels,SUA,LDL-C,NT-proBNP,hs-CRP,D-D and PCT are risk factors for AMI complicated with heart failure.
3.Interventional treatment of portal vein thrombosis via hepatic circular ligament approach during liver transplantation: a report of 3 cases
Chiyi CHEN ; Hao WANG ; Li ZHANG ; Qingjun GUO ; Honghai WANG ; Jisan SUN ; Guang CHEN ; Wentao JIANG
Chinese Journal of Organ Transplantation 2024;45(11):811-814
Three recipients with portal vein thrombosis experienced insufficient blood flow to transplanted liver due to residual thrombus after thrombectomy during liver transplantation. Alternative measures posed significant risks or technical challenges. To promptly restore blood flow, intraoperative intervention was performed via round ligament of donor liver for managing residual portal vein thrombus. Balloon dilation and vascular stenting effectively relieved local stenosis. After intervention, portal vein flow rate and volume fulfilled the standards and function of transplanted liver recovered smoothly. Follow-ups revealed unobstructed stents and no new thrombus formation. This simple, safe and efficacious technique has not been previously reported in the literature.
4.Analysis of the curative effect of combined treatment of renal calculi or upper ureteral calculi with double endoscopy
Jiahui CAI ; Guangren NONG ; Honghai LI ; Baode LU ; Yongping HUANG
China Modern Doctor 2024;62(32):34-37,81
Objective To investigate the efficacy of negative pressure combined ureteroscopy combined with flexible ureteroscopy holmium laser lithotripsy in the treatment of renal calculi or upper ureteral calculi with a maximum diameter of 2-4cm.Methods The data of patients with renal calculi or upper ureteral calculi with a maximum diameter of 2-4cm who were hospitalized inAffiliated Hospital of Youjiang Medical University for Nationalities from March 2023 to March 2024 were collected and divided into observation group(n=40)and control group(n=40).The observation group was treated with negative pressure combined ureteroscopy combined with flexible ureteroscopy for holmium laser lithotripsy,and control group was treated with nephroscope for percutaneous nephrolithotomy(PCNL).The operation time,postoperative hospital stay,changes of blood routine white blood cell(WBC)before and after operation,changes of urine routine WBC before and after operation,postoperative visual analogue score(VAS),one-stage stone clearance rate and postoperative complications were compared between two groups.Results The postoperative hospitalization time and VAS of observation group were significantly lower than those of control group(P<0.05).There was no significant difference in operation time,stone clearance rate,postoperative blood routine WBC and postoperative urine routine WBC between two groups(P>0.05).However,the blood routine WBC of two groups after operation was higher than that before operation(P<0.05).The overall stone clearance rate of two surgical methods was 86.25%,of which the stone clearance rate of observation group was 82.5%,and control group was 90%.There was no significant difference between two groups(P>0.05).Conclusion It is safe and effective to treat renal calculi;or upper ureteral calculi with a maximum diameter of 2-4cm by negative pressure combined ureteroscopy combined with flexible ureteroscopy holmium laser lithotripsy.It is expected to partially replace PCNL and become another safe and reliable operation for the treatment of renal calculi or upper ureteral calculi with a maximum diameter of 2-4cm.
5.Influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junction treated by neoadjuvant chemoradio-therapy combined with surgical resection: a prospective study
Peigang YANG ; Yuan TIAN ; Honghai GUO ; Bibo TAN ; Ping′an DING ; Yang LIU ; Zhidong ZHANG ; Yong LI ; Qun ZHAO
Chinese Journal of Digestive Surgery 2022;21(3):385-390
Objective:To investigate the influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junc-tion (AEG) treated by neoadjuvant chemoradiotherapy (nCRT) combined with surgical resection.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 120 AEG patients who were treated by nCRT combined with surgical resection in the Fourth Hospital of Hebei Medical University from March 2020 to March 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before nCRT were allocated into the experiment group, and patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before surgical resection were allocated into the control group. All patients received the same plan of nCRT combined with D 2 radical gastrectomy. Observation indicators: (1) grouping situations of the enrolled patients; (2) surgical and postoperative pathological situations; (3) postoperative complications and treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement date with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 120 patients were selected for eligibility. There were 85 males and 35 females, aged (60±9)years. There were 60 patients in the experiment group and 60 patients in the control group, respectively. (2) Surgical and postoperative pathological situations. Patients in the two groups underwent D 2 radical gastrectomy successfully, with R 0 resection. The number of lymph nodes harvest, the number of lymph nodes stained, the number of metastatic lymph nodes stained, the number of micro lymph nodes, the number of inferior mediastinal lymph nodes, the number of inferior mediastinal lymph nodes stained, cases in postoperative pathological stage N0, stage N1, stage N2, stage N3a were 40.6±13.9,20.1±7.7, 1.0(0,3.0), 8.1±2.8, 3.7±1.3, 2.0(1.0,2.0), 18, 13, 23, 6 in patients of the experiment group, respectively. The above indicators were 30.4±8.3, 12.7±3.5, 0(0,1.0), 6.2±2.0, 2.4±1.2, 1.0(0,1.0), 23, 21, 15, 1 in patients of the control group, respectively. There were significant differences in the above indicators between the two groups ( t=-5.01, 6.85, Z=-3.78, t=-4.04, -5.57, Z=-5.48, -2.12, P<0.05). (3) Postoperative complications and treatment. There were 5 cases of the experiment group and 7 cases of the control group with postoperative complications, showing no significant difference between the two groups ( χ2=0.37, P>0.05). The patients with postoperative complications were improved after symptomatic treatment. Conclusion:Compared with injection of carbon nanoparticle tracer 24 hours before surgical resection, injection of carbon nanoparticle tracer 24 hours before nCRT can improve the acquisition of lymph nodes in AEG treated by nCRT combined with surgical resection.
6.Effect of Tongxinluo capsule on improvement of cardiac function and expression of myocardial enzyme spectrum in patients with coronary heart disease after percutaneous coronary intervention
Chinese Journal of Postgraduates of Medicine 2022;45(4):348-351
Objective:To investigate the effects of Tongxinluo capsule on the improvement of cardiac function and the expression of myocardial enzyme spectrum in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:One hundred patients with coronary heart disease after PCI who received treatment in Hebei Xianghe County People′s Hospitalfrom April 2018 to April 2020 were enrolled and randomly divided into the observation group and the control group. The control group was given conventional treatment, while the observation group was treated with Tongxinluo capsule on the basis of the control group. Patients in both groups were treated for 3 months. The normal clinical remission after treatment was observed in the two groups. The improvement of cardiac function index left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and myocardial enzyme index aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzyme - MB (CK - MB), lactate dehydrogenase (LDH), troponin T (TnT) were compared between the two groups before and after the treatment.Results:After treated for 3 months, the total effective rate in the observation group was higher than that in the control group: 92.0%(46/50) vs. 76.0%(38/50), the difference was statistically significant ( χ2 = 4.76, P<0.05). After treated for 3 months, the levels of LVEDV and LVESV in two groups were decreased, and the level of LVEF in two groups was increased, and the levels of LVEDV and LVESV in the observation group were lower than those in the control group: (153.39 ± 8.35) ml/m 2 vs. (155.57 ± 9.32) ml/m 2, (103.49 ± 9.25) ml/m 2 vs. (109.65 ± 10.46) ml/m 2; the levels of LVEF in the observation group was higher than that in the control group: (58.14 ± 7.41)% vs. (54.59 ± 6.92)%, the differences were statistically significant ( P<0.05). After treated for 3 months, the levels of AST, CK, CK-MB, LDH, TnT in two groups were decreased, and the levels of above index in the observation group were lower than those in the control group: (38.14 ± 7.28) U/L vs. (45.04 ± 8.12) U/L, (637.15 ± 75.25) U/L vs. (756.24 ± 85.24) U/L, (553.28 ± 53.14) U/L vs. (632.17 ± 62.81) U/L, (162.43 ± 15.41) U/L vs. (181.74 ± 19.25) U/L, (0.32 ± 0.15) μg/L vs. (0.39 ± 0.11) μg/L, the differences were statistically significant ( P<0.05). Conclusions:The application of Tongxinluo capsule in patients with coronary heart disease after PCI can effectively alleviate clinical symptoms, improve cardiac function, and regulate the enzyme activity of the body.
7.Laparoscopic or robotic serosa muscular layer circumferential incision combined with mucosal layer cutting and closure for gastrointestinal mesenchymal tumors at difficult sites of the stomach
Honghai GUO ; Yiyang HU ; Peigang YANG ; Yuan TIAN ; Dong WANG ; Zhidong ZHANG ; Xuefeng ZHAO ; Ping'an DING ; Yang LIU ; Yong LI ; Qun ZHAO
Chinese Journal of General Surgery 2022;37(11):817-820
Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.
8.Research on the characteristics of Tibetan Medicine for treating orthopedics and traumatological diseases based on data mining
Qingwang LU ; Honghai ZHOU ; Junming TIAN ; Jilin LI ; Dongyang LI ; Xinyu HE ; Yan LU
International Journal of Traditional Chinese Medicine 2022;44(11):1287-1291
Objective:To analyze the medication rule of treating orthopedics in Tibetan Medicine by data mining, in order to summarize the characteristics and theory of ethnic minorities medicine for treating orthopedics and traumatology.Methods:By collecting the treatment methods of orthopedics and traumatologic diseases in books of Chinese Materia Medica·Tibetan Medicine Volume and Chinese Medical Encyclopedia·Tibetan Medicine to analyze the frequency, cluster and association rules of Tibetan Medicines by using Office Excel 2019, IBM SPSS Statistics 26.0 and IBM SPSS modeler 14.1 respectively. Results:Among the 202 Tibetan Medicine prescriptions of Orthopedic Department, 338 belongs to Chinese medicines. The top 3 Chinese medicines that are frequently appeared are Chebulae Fructus, Inula racemosa Hook.f, and Carthami Flos. The properties of those medicines are mainly cold, warm and cool, and the tastes are mainly pungent, bitter and sweet; the meridians mainly belong to liver, lung, stomach and spleen; The priscriptions mainly cover four kinds of diseases: trauma, arthralgia syndrome, lumbosacral tendon injury, chest and back tendon injury. The four kinds of cluster combinations were obtained. The core Chinese medicines were Chebulae Fructus, Terminaliae Belliricae Fructus, Phyllanthi Fructus, Cassiae Semen, Olibanum, Abelmoschus moschatus, and the common medicine pair were Chebulae Fructus- Terminaliae Belliricae Fructus, Abelmoschus moschatus- Cassiae Semen, Olibanum- Abelmoschus moschatus and so on. Conclusions:Tibetan Medicines treat orthopedics and traumatological diseases with antipyretic medicines as the main yellow water, followed by blood activating, Qi regulating and wind dampness removing medicines. With Sanguo Decoction and Sanhuang water of Tibetan medicine as the core, they are often combined with other antipyretic and blood cooling medicines and bone connecting medicines. Tibetan Medicine pays attention to the application of dry yellow water theory, which reflects the role of the core theory of Qingxie method and yellow water theory of Tibetan Medicine in the diagnosis and treatment of orthopedic and traumatologic diseases.
9.The application value of estimating 24 h urinary iodine excretion in the evaluation of individual iodine nutrition level
Honghai LI ; Shuling WANG ; Yong ZHANG ; Ning WANG ; Jian CHEN ; Xiao LIU
Chinese Journal of Endemiology 2021;40(5):410-413
Objective:To explore the application value of creatinine correction method in estimating 24 h urinary iodine excretion of healthy adults.Methods:Healthy adults(half males and half females) aged 18 to 59 yesrs old in Tangshan City were selected as the research subjects. Random urine within 1 d, morning urine and 24 h urine samples of 5 d in a row of all subjects were collected to detect urinary iodine and creatinine concentrations. Twenty-four hours urinary iodine excretion was estimated by creatinine correction formula [24 h urinary iodine excretion estimated value(μg/d) = urinary iodine/creatinine concentration ratio (μg/g Cr) × 24 h urinary creatinine excretion (g Cr/d)]. The estimated value of 24 h urinary iodine excretion obtained from random urine within 1 d and continuous 5 d morning urine corrected by creatinine were studied by the coefficient of variation, and compared with the measured value of 24 h urinary iodine excretion.Results:The coefficient of variation of the estimated 24 h urinary iodine excretion of random urine within 1 d ranged from 8.8% - 20.2%, with an average value of 13.1%; the coefficient of variation of 24 h urinary iodine excretion estimated value from continuous 5 d morning urine and the 24 h urinary iodine excretion measured value ranged from 4.7% - 17.2% and 4.0% - 10.4%, and the average values were 10.1% and 6.4%, respectively. In the detection of random urine within 1 d, there was no significant difference between the 24 h urinary iodine excretion estimated value of the first, second, third, and forth time random urine and the 24 h urinary iodine excretion measured value ( P > 0.05). In the detection of continuous 5 d morning urine, there were no significant differences in the 24 h urinary iodine excretion estimated value of the first, second, third, forth and fifth day compared with the 24 h urinary iodine excretion measured value on the same day, respectively ( P > 0.05). Conclusions:When the daily creatinine excretion is accurately known, the estimated 24 h urine iodine excretion obtained by the creatinine correction method can better reflect the actual 24 h urinary iodine excretion. Further study on prediction criteria of creatinine excretion suitable for Chinese people will help to better detect the iodine intake of corresponding individuals.
10.Risk factors relating to lymphatic leakage and prediction scoring model after radical gastrectomy for gastric carcinoma
Ping'an DING ; Zhidong ZHANG ; Peigang YANG ; Yuan TIAN ; Honghai GUO ; Yang LIU ; Tao ZHENG ; Dong WANG ; Yong LI ; Qun ZHAO
Chinese Journal of General Surgery 2021;36(7):530-534
Objective:To explore the risk factors of lymphatic fistula after radical gastric cancer operation.Methods:We retrospectively analyze the clinicopathological data of gastric cancer patients who underwent radical surgery from May, 2019 to May, 2020 at the Third Department of Surgery, Fourth Hospital of Hebei Medical University, and analyze the risk factors impacting postoperative lymphatic leakage,for the establishment of the risk prediction scoring model.Results:A total of 487 patients with gastric cancer underwent radical gastrectomy, of which 32 patients (6.6%) had lymphatic leakage . Multivariate logistic regression analysis showed that hypoproteinemia before surgery (95% CI: 1.222-7.357, P=0.016), the lesion is located in the cardia-fundus of the stomach (95% CI: 1.117-6.788, P=0.028),stage T3-T4 (95% CI: 1.149-25.676, P=0.033), operation time ≥4 h (95% CI: 1.469-11.480, P=0.007), combined organ resection (95% CI: 1.106-12.886, P=0.034), D2+ lymph node dissection (95% CI: 1.969-11.510, P=0.001), anemia (95% CI: 1.271-9.392, P=0.015) were an independent risk factors. Equation based on multi-factor Logistic regression: logit( P)=-9.624+1.098×X 1+1.013×X 2+1.692×X 3+1.413×X 4+1.328×X 5+1.560×X 6+1.240×X 7 was estaslished, using Hosmer. Lemeshow test detects the goodness of fit of the regression equation ( P=0.348). The area under the ROC curve was 0.856 (95% CI: 0.787-0.926, P<0.001); the probability of lymphatic leakage when scores ≥4 points was 14.1%, when scores <4 points ,the probability of leakage was 2.5%. Conclusion:A risk prediction scoring model for lymphatic leakage after radical gastrectomy, can identify patients with high risk after surgery

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