1.Study on the role of butyric acid-producing bacteria in periodontitis-induced interference with long bone homeostasis in mice fed a high-fat/high-sugar diet
XU Zhonghan ; YAO Yujie ; WANG Xinyue ; SONG Shiyuan ; BAO Jun ; YAN Fuhua ; TONG Xin ; LI Lili
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(6):445-456
Objective:
To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases.
Methods:
This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same.
Results:
①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05).
Conclusion
Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.
2.Effects of Zuogui Jiangtang Yishen Formula in regulating the NLRP3/caspase-1/GSDMD signaling axis on pyroptosis in rats with diabetic kidney disease
Shujuan Hu ; Xuhua Li ; Yao Peng ; Lili Chen ; Rong Yu ; Yajun Peng
Digital Chinese Medicine 2025;8(3):379-388
Objective:
To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD).
Methods:
Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18.
Results:
Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05).
Conclusion
ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
3.Application of MRI compilation sequence for predicting lymphovascular space invasion status in early cervical cancer
Zebo HUANG ; Wenwei TANG ; Yao YAO ; Tong LIANG ; Zhongfu TIAN ; Lili WANG ; Hailei GU
Journal of Practical Radiology 2024;40(3):422-425,429
Objective To assess the value of magnetic resonance imaging compilation(MAGiC)sequence in predicting lympho-vascular space invasion(LVSI)in early cervical cancer.Methods The data of 48 patients with cervical cancer confirmed by pathology were collected retrospectively,and classified into LVSI-positive group(n=29)and LVSI-negative group(n=19)according to postop-erative pathological results.MAGiC sequence images of patients were obtained before injecting contrast agents,then the region of interest(ROI)was delineated along the largest dimension edge of the lesion,and T1,T2 and proton density(PD)values were automatically generated by the software.Predictors were screened by univariate analysis and receiver operating characteristic(ROC)curves were drawn to assess their diagnostic efficacy for predicting LVSI in cervical cancer.Results Significant differences were found in T1 and PD values between LVSI-positive and LVSI-negative groups(P=0.003,P=0.017).There were no significant differences in T2 values between the two groups(P=0.414).The area under the curve(AUC)for T1 and PD values to predict LVSI status were 0.73 and 0.721,respectively.Conclusion LVSI-positive group of cervical cancer has lower T1 and PD values than LVSI-negative group based on MAGiC sequence.The MAGiC sequence has a certain application value for predicting LVSI status in early cervical cancer.
4.Correlation between platelet to lymphocyte ratio,neutrophil to lymphocyte ratio and carotid atherosclerotic plaque in patients with type 2 diabetes mellitus
Shufan YAO ; Xiaogang WENG ; Lili ZHANG
Journal of Xinxiang Medical College 2024;41(1):53-59
Objective To explore the correlation between platelet to lymphocyte ratio(PLR),neutrophil to lymphocyte ratio(NLR)and carotid atherosclerotic(CAS)plaque in patients with type 2 diabetes(T2DM),and the predictive value of PLR and NLR for T2DM complicated with CAS plaque.Methods A total of 369 T2DM patients admitted to the Department of Endocrinology,the Third Affiliated Hospital of Xinxiang Medical University from September 2019 to November 2021 were se-lected as research subjects.The clinical data such as gender,age,course of disease,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),personal history,and history of past illness of patients were collected by searching the electronic medical record system.Neutrophil(NC)count,lymphocyte count(LC)and platelet(PLT)count were detected by fully automated blood routine analyzer,and PLR,NLR were calculated;the levels of fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),high-density lipoprotein-cholesterol(HDL-C)and low-density lipoprotein-cholesterol(LDL-C)were detected by biochemical analyzer;the level of glycosylated hemoglobin(HbA1c)were detected by high-performance liquid chromatography.The T2DM patients were divided into T2DM uncomplicated with CAS plaque group(n=94)and T2DM complicated with GAS plaque group(n=275)based on whether they complicated with CAS plaque or not;the general clinical data,blood indicators,and PLR,NLR of patients were compared between the two groups.The T2DM patients were divided into non plaque group(group A,n=94),1 plaque group(group B,n=79),2 plaque group(group C,n=89),and 3 or more plaques group(group D,n=107)based on the number of CAS plaques;the indicators with statistical differences between T2DM uncomplicated with CAS plaque group and T2DM complicated with CAS plaque group of patients were compared among the four groups.According to the PLR quartile,the patients were divided into P1 group(PLR≤94.87,n=93),P2 group(94.87<PLR≤117.30,n=91),P3 group(117.30<PLR ≤ 148.53,n=93),and P4 group(PLR>148.53,n=92),and the detection rate of CAS plaques of patients was compared among the four groups;according to the NLR quartile,the patients were divided into N1 group(NLR≤1.59,n=92),N2 group(1.59<NLR≤1.93,n=92),N3 group(1.93<NLR≤2.50,n=93),and N4 group(NLR>2.50,n=92),and the detection rate of CAS plaque of patients was compared among the four groups.The risk factors of T2DM complicated with CAS plaque was analysed by multivariate logistic regression analysis,and the predictive efficacy of PLR and NLR for T2DM complicated with CAS plaque were evaluated by receiver operating characteristic(ROC)curve.Results The age,course of T2DM,proportion of patients combined with hyper-tension,SBP,PLR,and NLR of patients in the T2DM complicated with CAS plaque group were significantly higher than those in the T2DM uncomplicated with CAS plaque group,while LC and TG levels were significantly lower than those in the T2DM uncomplicated with CAS plaque group(P<0.05);there was no significant difference in gender,proportion of patients com-bined with hyperlipidemia,proportion of smoking history,proportion of drinking history,and the levels of DBP,BMI,NC,PLT,TC,HDL-C,LDL-C,FBG,HbA1c between the T2DM uncomplicated with CAS plaque group and T2DM complicated with CAS plaque group(P>0.05).The age,proportion of patients combined with hypertension,course of T2DM,SBP,PLR,and NLR of patients in group B,group C,and group D were significantly higher than that in group A,while LC level was significantly lower than that in group A(P<0.05).The TG level of patients in group D was significantly lower than those in group A(P<0.05);there was no statistically significant difference in TG level of patients among group A,group B,and group C(P>0.05).The age,proportion of patients combined with hypertension,and course of T2DM of patients in group C and group D were significantly higher than those in group B,while the SBP of patients in group D was significantly higher than that in group B(P<0.05);there was no statistically significant difference in SBP of patients between group C and group B(P>0.05).The age,proportion of patients combined with hypertension,course of T2DM,and SBP of patients in group D were significantly higher than those in group C(P<0.05).There was no statistically significant difference in the levels of LC,TG,and PLR of patients among group B,group C,and group D(P>0.05).The NLR of patients in group D was significantly higher than that in group B(P<0.05);there was no statistically significant difference in NLR of patients between group C and group B(P>0.05),and there was no statistically significant difference in NLR of patients between group D and group C(P>0.05).The detection rate of CAS plaques of patients in P1 group,P2 group,P3 group,and P4 group showed a significant increase trend(x2=30.610,P=0.000);and the detection rate of CAS plaques of patients in N1 group,N2 group,N3 group,and N4 group showed a significant increase trend(x2=35.170,P=0.000).Multivariate logistic regression analysis showed that age,PLR,and NLR were independent risk factors for T2DM complicated with CAS plaque(odds ratio=1.107,1.017,1.940;P<0.05).The opti-mal cutoff value of PLR in predicting T2DM complicated with CAS plaque was 119.95,with an area under the curve of 0.680,a sensitivity of 54.7%,and a specificity of 76.3%;the optimal cutoff value of NLR in predicting T2DM complicated with CAS plaque was 1.97,with an area under the curve of 0.698,a sensitivity of 56.5%,and a specificity of 79.6%.Conclusion PLR and NLR are associated with T2DM complicated with CAS plaque,which are independent risk factors for T2DM compli-cated with CAS plaque,and have certain predictive value for T2DM complicated with CAS plaque.
5.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
6.Differential effects of APOE polymorphism in neurotoxicity-responsive astrocytes induced by inflammatory factor
Yan WANG ; Xiaohui LI ; Yao JI ; Lili CUI ; Yujie CAI
Journal of Jilin University(Medicine Edition) 2024;50(1):33-41
Objective:To discuss the differential effects of apolipoprotein E(APOE)gene polymorphism in the neurotoxicity-reactive astrocytes,and to provide the theoretical basis for the study of the pathogenesis of Alzheimer's disease(AD).Methods:The primary cortical astrocytes from the APOE-knockout mice(APOE-/-)were isolated and cultured in vitro,and the purity of the cells was identified by immunofluorescence staining.The human APOE3 and APOE4 recombinant over-expression plasmids were constructed and separately transfected into the primary APOE-/-astrocytes,and the APOE-/-primary cells were regarded as control.Western blotting method was used to detect the expression levels of APOE and glial fibrillary acidic protein(GFAP)proteins in the cells;enzyme-linked immunosorbent assay(ELISA)method was used to detect the APOE level in the cellular culture supernatant.The inflammatory models were prepared with the primary astrocytes transfected with APOE3 and APOE4 and co-stimulated with interleukin-1α(IL-1α),tumor necrosis factor(TNF),and complement C1q.The cells were divided into APOE3+PBS group,APOE4+PBS group,APOE3+IL-1α+TNF+ C1q group,and APOE4+IL-1α+TNF+C1q group.Cell immunofluorescence staining method was used to observe the morphology of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of glypican 4(Gpc4),glypican 6(Gpc6),thrombospondin 1(Thbs1),thrombospondin 2(Thbs2),SPARC-like protein 1(Sparcl1)and glial cell line derived neurotrophic factor(GDNF),C3,and S100 calcium binding protein B(S100B)mRNA in the cells in various groups;microsphere phagocytosis assay was used to detect the phagocytic capacities of the cells in various groups;Western blotting was used to detect the protein expression levels of B-cell lymphoma 2(Bcl-2),and cysteinyl aspartate specific protease-3(Caspase-3)proteins in the cells in various groups.Results:Compared with APOE-/-group,the expression levels of APOE and GFAP proteins in the cells and the APOE level in the cellular culture supernatant in transfected APOE3 and transfected APOE4 groups were increased(P<0.01).The fluorescence microscope observation results showed that compared with APOE3+PBS and APOE4+PBS groups,the astrocytic processes in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α+TNF+Cq1 group became shorter and the cell bodies became larger;compared with APOE3+IL-1α +TNF+Cq1 group,the astrocytic processes in APOE4+IL-1α +TNF+Cq1 group were even shorter.Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.05 or P<0.01).Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of GDNF mRNA in the cells in APOE3+IL-1α+TNF+Cq1 group and APOE4+ IL-1α +TNF+Cq1 group were decreased(P<0.01),and the expression levels of C3 and S100B mRNA were increased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression level of GDNF mRNA in the cells in APOE4+IL-1α+TNF+Cq1 group was decreased(P<0.05),and the expression levels of C3 and S100B mRNA were increased(P<0.05).Compared with APOE3+ PBS group and APOE4+PBS group,the numbers of hagocytosis of microspheres in the cells in APOE3+ IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased;compared with APOE3+IL-1α+TNF+Cq1 group,the number of hagocytosis of microspheres in the cells in APOE4+IL-1α+TNF+Cq1 group was significantly decreased.Compared with APOE3+PBS group and APOE4+PBS group,the expression levels of Bcl-2 protein in the cells in APOE3+IL-1α+TNF+ Cq1 group and APOE4+IL-1α +TNF+Cq1 group were decreased(P<0.05 or P<0.01)and the expression levels of Caspase-3 protein were significantly increased(P<0.01);compared with APOE3+ IL-1α+TNF+Cq1 group,the expression level of Bcl-2 protein in the cells in APOE4+IL-1α+TNF+ Cq1 group was decreased(P<0.01),and the expression level of Caspase-3 protein was increased(P<0.05).Conclusion:The APOE4 genotype has a stronger ability to induce the inflammatory factors compared with APOE3;it can lead to a neurotoxicity-reactive astrocyte phenotype,increase the neurotoxicity,affect the astrocyte apoptosis,and aggravate the neuron damage.
7.Effect and Mechanism of Zuogui Jiangtang Yishen Prescription on Diabetic Kidney Disease in Rats via Regulation of MiRNA-27a/Wnt/β-catenin Pathway
Shujuan HU ; Xuhua LI ; Xiu LIU ; Yao PENG ; Lili CHEN ; Rong YU ; Yajun PENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):90-97
ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription (ZJYP) in Goto-Kakizaki (GK) rats with early-stage diabetic kidney disease (DKD). MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding, with fasting blood glucose (FBG) ≥ 11.1 mmol·L-1 and urinary albumin/creatinine ratio (ACR) ≥ 30 mg·g-1 used as model criteria. After successful modeling, DKD rats were randomly divided into five groups (n=10 in each group): the model group, the western medicine group treated with dapagliflozin (1.0 mg·kg-1·d-1), low-, medium-, and high-dose ZJYP groups (4.9, 9.9, 19.9 g·kg-1·d-1 by gavage). Ten Wistar rats served as normal controls, with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR, FBG, body weight, and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect miRNA-27a, Wnt, and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group, the FBG levels in DKD rats of the model group increased significantly at 0, 2, 4, 6, and 8 weeks of drug intervention (P<0.05), and urinary ACR increased significantly at 0, 4, 8 weeks (P<0.05). Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix, slight thickening of the basement membrane, and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a, Wnt, and β-catenin were significantly higher in the model group than in the normal group (P<0.05). Renal Wnt and β-catenin protein levels were also significantly higher in the model group (P<0.05). After drug intervention, the FBG levels in the low-, medium-, and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks (P<0.05). The urinary ACR also showed a dose-dependent decrease in the low-, medium-, and high-dose ZJYP groups, but the differences were not statistically significant. There were no significant differences in liver function, renal function, renal index, or routine blood lipid test results among the low-, medium-, and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group, with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a, Wnt, and β-catenin were significantly lower in the high-dose ZJYP group (P<0.05), and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group (P<0.05). The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group, but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats, thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.
8.Observation on the outcome of occupational chronic benzene poisoning treated with acupuncture combined with Du-Moxibustion
Ying ZHENG ; Lili LAI ; Xiaofeng DENG ; Chunyue FAN ; Jin WU ; Min OU ; Shufang YAO ; Hailan WANG
China Occupational Medicine 2024;51(2):210-213
ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.
9.The value of EIGR in predicting prognosis of patients with acute ischemic stroke with large vessel occlusion
Xiaohui LI ; Xuan WANG ; Xiaoquan XU ; Hua LI ; Li JI ; Lina MAO ; Fen WAN ; Yao WANG ; Lili JIANG ; Xufeng CHEN ; Lei JIANG
Chinese Journal of Emergency Medicine 2024;33(10):1421-1426
Objective:To investigate the effect of Early infarct growth rate(EIGR) on the prognosis of patients with acute large vessel occlusive ischemic stroke.Methods:A total of 164 patients with acute large vessel occlusive ischemic stroke were enrolled in the emergency department of the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to December 31, 2022.According to the change of the National Institutes of Health Stroke Scale (NIHSS) score at admission and 72 h after treatment, the patients were divided into good prognosis group and poor prognosis group. The basic clinical data of the two groups were observed and compared. The risk factors of poor prognosis were analyzed by univariate regression. The effect of EIGR on prognosis after age stratification was further analyzed.Results:Comparing the clinical data of the two groups, there was no difference in EIGR (mL/h) (7.67 vs. 8.24, P=0.211) between the two groups. The product between EIGR and age was included as the interaction term, and the result of the interaction term in the model was statistically significant ( OR=1.002, 95% CI: 1.000-1.003, P=0.032) .Moreover, the result was still statistically significant after adjusting for relevant variables (gender, history of hypertension, history of atrial fibrillation, history of diabetes, history of coronary heart disease, and history of stroke) ( OR=1.002, 95% CI:1.000-1.003, P=0.027). Subgroup analysis was performed according to the median age (71 years). In the elderly group, the proportion of poor prognosis was higher with fast core infarction growth rate defined by 25 mL/h and 15 mL/h ( P < 0.05).In the younger age group, there was no significant difference in the proportion of poor prognosis in the fast core infarction growth rate compared with the slow type ( P > 0.05). Conclusions:EIGR can predict the early clinical outcome early in elderly patients with large vessel occlusive ischemic stroke.
10.Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province
Gaixiang XU ; Weimei JIN ; Baodong YE ; Songfu JIANG ; Chao HU ; Xin HUANG ; Bingshou XIE ; Huifang JIANG ; Lili CHEN ; Rongxin YAO ; Ying LU ; Linjie LI ; Jin ZHANG ; Guifang OUYANG ; Yongwei HONG ; Hongwei KONG ; Zhejun QIU ; Wenji LUO ; Binbin CHU ; Huiqi ZHANG ; Hui ZENG ; Xiujie ZHOU ; Pengfei SHI ; Ying XU ; Jie JIN ; Hongyan TONG
Chinese Journal of Hematology 2024;45(6):549-555
Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.


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