1.Regulation of Renal Interstitial Fibrosis-related Pathways by Traditional Chinese Medicine: A Review
Dandan WEI ; Shanshan LI ; Yongjie WANG ; Hongling WANG ; Zongyao WU ; Qingbo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):254-265
Renal interstitial fibrosis (RIF) is a common pathological change process from the development of various chronic nephropathies to the end stage, and it is an important histological manifestation of renal function decline. At present, no effective anti-fibrosis drugs have been found in clinical practice. In recent years, with the continuous development of traditional Chinese medicine (TCM) pharmacology, molecular biology, system biology, and network pharmacology, the research on regulating RIF with TCM monomer, single TCM, TCM compound, Chinese patent medicine, and TCM injection is deepening. Among them, Jianpi Yishen recipe, Shendi Bushen capsules, Jianzhong Bushen Xiaozheng decoction, Liuwei Dihuangtang, and Lycium barbarum polysaccharides can regulate transforming growth factor-β/small mother against decapentaplegic (TGF-β1/Smads), Wnt/β-catenin, and neurogenic locus notch homolog protein (Notch) signaling pathways. Wulingsan, Zhenwutang, pachymic acid ZA, pachymic acid ZC, and pachymic acid ZD, which mainly induce diuresis, can regulate the Wnt/β-catenin signaling pathway. Hirudin, curcumin, and Fuzheng Huayu recipe, which mainly promote blood circulation, can inhibit inflammation-related pathways such as p-nuclear transcription factor-κB (NF-κB), Toll-like receptor 4/p-nuclear transcription factor-κB (TLR4/NF-κB), and Janus kinase 2/signal transducer and activator of transcription 3 (JAK/STAT), so as to achieve anti-inflammatory and anti-oxidation effects and alleviate the progression of RIF. Shenshuai Xiezhuo decoction, Shenkang injection, and Shenshuai recipe, which are mainly used for invigorating Qi, removing blood stasis, and removing turbidity, can inhibit transdifferentiation of pericytes-myofibroblasts through vascular endothelial growth factor receptor (VEGFR) signaling pathway. At present, there are many studies on the regulation of the RIF signaling pathway by TCM, but there is a lack of a systematic summary. In this study, by combing the signaling pathway of TCM in the treatment of RIF, the effective target of TCM treatment is screened, and its possible mechanism is found, which provides new ideas for clinical treatment and new drug research and development.
2.Diagnosis and treatment of gastrointestinal bleeding after kidney transplantation
Handong DING ; Qin WANG ; Guiyi LIAO ; Zongyao HAO
Journal of Peking University(Health Sciences) 2024;56(5):902-907
Objective:To analyze the clinical characteristics of acute and chronic gastrointestinal bleeding in patients with end-stage renal disease(ESRD)after kidney transplantation,to improve the understanding of the causes,diagnosis,treatment and prevention of this complication,and to improve the management of patients with gastrointestinal bleeding after kidney transplantation.Methods:The clini-cal,imaging and pathological data of patients with gastrointestinal bleeding after kidney transplantation in the Department of Urology of The First Affiliated Hospital of Anhui Medical University from August,2015 to December,2020 were collected.The etiology,early clinical manifestations,abnormal laboratory tests and examinations,treatment procedures,late prevention and treatment measures and outcomes of gastro-intestinal bleeding were retrospectively studied,and the relevant literature was summarized and reviewed.Results:A total of 17 patients were included in this study.Nine patients had chronic small amount of bleeding,hemoglobin gradually decreased,melena and fecal occult blood positive in the early stage,and the general condition was good,vital signs were stable,and were cured by drug treatment.Gastroscopy showed small ulcers with active bleeding foci in 2 cases,and the bleeding was stopped by titanium clips,and the prognosis was good.Gastroscopy showed that the anterior wall longitudinal ulcer at the junction of gastric antrum body was not effective in 1 case,and the small branch of right gastroepithelial artery was embolized,and the patient recovered and discharged after 2 weeks.Gastroscopy showed deep pit ulcer at the lesser curvature of gastric antrum in 1 patient,who underwent distal gastroduodenal artery emboliza-tion and had a good prognosis.Gastroscopy showed huge multiple ulcers in the stomach and duodenal bulb in 2 patients,who underwent subtotal gastrectomy and partial duodenectomy,duodenal stump exclu-sion and remnant gastrojejunostomy.One patient recovered and was discharged,and the other patient died of rebleeding on the 12th day after surgery.Two cases of diverticulum underwent surgical resection of diverticulum,and the prognosis was good.Conclusion:The onset of gastrointestinal hemorrhage in kidney transplant patients is insidious,and the condition is acute or slow,which can cause different de-grees of damage to the patient and the transplanted kidney.Active prevention,early diagnosis,timely drug treatment,if the effect is not good,decisive endoscopic titanium clip hemostasis,transvascular in-terventional embolization,and even surgical treatment can minimize the harm of gastrointestinal bleeding.
3.Intervention effect and mechanism of breviscapine on hepatic fibrosis in rats
Dandan WEI ; Shanshan LI ; Minghao ZHANG ; Yurun WEI ; Hongling WANG ; Shuangshuang CHAI ; Jingjing YIN ; Min ZHANG ; Han ZHAO ; Zongyao WU ; Kuicheng ZHU ; Qingbo WANG
China Pharmacy 2024;35(6):671-677
OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis (HF) in rats based on the transforming growth factor-β(1 TGF-β1)/Smad2/extracellular signal-regulated protein kinase 1(ERK1) and Kelch-like epichlorohydrin-associated protein 1(Keap1)/nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathways. METHODS Totally 60 rats were randomly divided into normal control group, model group, breviscapine low-dose, medium-dose and high-dose groups (5.4, 10.8, 21.6 mg/kg), and colchicine group (positive control, 0.45 mg/kg), with 10 rats in each group, half male and half female. Except for the normal control group, HF model of the other groups was induced by carbon tetrachloride. Subsequently, each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase (ALT) and aspartate aminotransferase (AST)in serum, those of ALT, AST, superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH- Px) in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1, Smad2, ERK1, Nrf2, Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group, the model group showed large areas of white nodular lesions in the liver, obvious inflammatory cell infiltration and collagen fiber deposition. The body weight, the levels of SOD and GSH-Px in liver tissue, the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group (P<0.05); the liver coefficient, the percentage of Masson staining positive area, ALT and AST levels of serum and liver tissue, MDA level of liver tissue, the protein and mRNA expressions of TGF-β1, Smad2, ERK1 and Keap1 were significantly increased (P<0.05). Compared with the model group, the liver lesions of rats in each drug group were improved, and the above quantitative indexes were generally reversed (P<0.05). CONCLUSIONS Breviscapine has a good intervention effect on HF rats, which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.
4.Is There a Two-Way Risk between Decreased Testosterone Levels and the Progression and Prognosis of Chronic Kidney Disease? A Cohort Study Based on the National Health and Nutrition Examination Survey Database
Jiashan PAN ; Zhenming ZHENG ; Xike MAO ; Dekai HU ; Wenbo WANG ; Guiyi LIAO ; Zongyao HAO
The World Journal of Men's Health 2024;42(2):429-440
Purpose:
The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone.
Materials and Methods:
This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD’s effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone.
Results:
From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (β=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001).
Conclusions
The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.
5.Diagnostic value of ATP stress myocardial perfusion imaging in detecting coronary artery disease with quantitative coronary angiography as the gold standard
Yan DU ; Yawen WANG ; Hailong ZHANG ; Zongyao ZHANG ; Lei WANG ; Wei FANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(2):70-74
Objective:To assess the diagnostic value of ATP stress myocardial perfusion imaging(MPI) in detecting coronary heart disease (CAD) with quantitative coronary angiography (QCA) as the gold standard.Methods:A total of 95 consecutive patients (65 males, 30 females, age (56.2±8.5) years) who underwent ATP stress/rest MPI and coronary angiography (CAG) within one month in Fuwai Hospital, Chinese Academy of Medical Sciences from May 2018 to December 2018 were enrolled prospectively. The adverse reactions of ATP stress test were observed. Semi-quantitative analysis was performed on MPI results, and the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) were obtained. Quantitative analysis was performed on CAG images, and the degree of QCA coronary artery stenosis was analyzed. Using QCA as the gold standard, the diagnostic efficiency of ATP stress MPI was calculated. Pearson correlation analysis was performed to analyzed the relationship between SSS and the degree of QCA coronary artery stenosis.Results:In 95 cases, the incidence of adverse reactions in ATP stress test was 73.7%(70/95), which could be relieved automatically after drug withdrawal. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ATP stress MPI in diagnosing coronary artery stenosis ≥50% were 45.3%(24/53), 81.0%(34/42), 75.0%(24/32), 54.0%(34/63) and 61.1%(58/95) respectively, which were 15/16, 78.5%(62/79), 46.9%(15/32), 98.4%(62/63), and 81.1%(77/95) respectively in diagnosing coronary artery stenosis ≥70%. There was moderate correlation between SSS and the degree of QCA coronary artery stenosis ( r=0.418, P=0.017). Conclusion:ATP stress MPI has a clinical value in the diagnosis of myocardial ischemia in CAD.
6.Quantitative assessment of right ventricular myocardial blood flow with SPECT in pulmonary hypertension animal models
Yan DU ; Kai HAN ; Zongyao ZHANG ; Ruoxi SUN ; Lei WANG ; Wei FANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(7):412-417
Objective:To explore the changes of right ventricular myocardial perfusion in pulmonary arterial hypertension (PAH) pig models with a quantitative analysis technique based on dynamic SPECT myocardial perfusion imaging, and analyze the relationship between myocardial blood flow, hemodynamics and right ventricular function.Methods:Eleven Chinese miniature pigs (all males, 6-8 months old) weighing 25-30 kg were selected. The PAH models were established by ligating the main pulmonary artery and embolizing the right lower pulmonary artery. After the models were established, dynamic myocardial perfusion imaging with one-day resting/adenosine stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed, and the quantitative parameters of left and right ventricles were obtained, including stress myocardial blood flow (SMBF), rest myocardial blood flow (RMBF) and myocardial flow reserve (MFR: the ratio of stress to rest myocardial blood flow). Right heart catheterization was performed to evaluate the mean pulmonary arterial pressure (mPAP), and the right heart function index tricuspid annular plane systolic excursion (TAPSE) was measured by transthoracic echocardiography. According to TAPSE, animals were divided into right heart function preserved group ( n=5, TAPSE≥17 mm) and right heart dysfunction group ( n=4, TAPSE<17 mm). Pearson correlation analysis and the independent-sample t test were used for data analysis. Results:Nine experimental pig models were established with increased mPAP of (38.1 ± 11.6 ) mmHg (1 mmHg=0.133 kPa). Myocardial perfusion imaging showed clear radiotracer uptake in the right heart and myocardial hypertrophy. There was a significant positive correlation between right ventricular myocardial RMBF ((0.71±0.13) ml·min -1·g -1) and mPAP ( r=0.94, P< 0.001). The SMBF in the decreased right ventricular function group was significantly lower than that in the preserved right ventricular function group ((1.66±0.35) vs (2.24±0.30) ml·min -1·g -1;t=2.68, P=0.032). Conclusion:SPECT myocardial blood flow quantification can be used to evaluate the right ventricular myocardial blood flow in pig models of PAH.
7.Comparison of IQ-SPECT and low energy high-resolution collimator SPECT in clinical application
Kai HAN ; Hailong ZHANG ; Zongyao ZHANG ; Xiaoxin SUN ; Lei WANG ; Wei FANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(6):357-362
Objective:To investigate differences in cardiac function and perfusion parameters measured by IQ-SPECT and low energy high-resolution (LEHR)-SPECT, as well as effects of scattering correction (SC) and CT attenuation correction (AC) on myocardial perfusion imaging.Methods:From May 2020 to September 2020, 80 patients (58 males, 22 females, age (57±10) years) who underwent SPECT myocardial perfusion imaging were retrospectively enrolled in Fuwai Hospital. According to the standardized left ventricular end-diastolic diameter of body surface measured by two-dimensional echocardiography, patients were divided into 2 groups: A group ( n=34) with significantly enlarged left ventricle and B group ( n=46) with no significant enlargement of left ventricle. LEHR-SPECT and IQ-SPECT gated myocardial perfusion imaging were performed in all patients. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), summed rest score (SRS) and total perfusion defect (TPD) were measured. Parameters measured by two methods and differences before and after SC and AC were compared by using paired t test and Wilcoxon signed rank test. The correlation was analyzed by Pearson correlation or Spearman rank correlation analyses, and the consistency was analyzed by Bland-Altman analysis. Results:In A group, EDV, EF and SRS measured by IQ-SPECT were significantly lower than those assessed by LEHR-SPECT after SC and AC (EDV: (257±137) vs (276±154) ml, EF: (21±11)% vs (26±13)%, SRS: 17(6, 25) vs 18(8, 28); t values: -2.63, -7.46, z=-2.14, all P<0.05); all parameters measured by LEHR-SPECT and IQ-SPECT had well correlation ( r values: 0.965, 0.969, 0.967, rs values: 0.920, 0.960, all P<0.001) and consistency. In B group, EDV and EF measured by IQ-SPECT were significantly lower than those assessed by LEHR-SPECT after SC and AC (EDV: (96±40) vs (107±39) ml, EF: (46±15)% vs (54±16)%; t values: -6.23, -10.71, both P=0.001); SRS and TPD measured by IQ-SPECT after SC and AC were significantly lower than non-SC and non-AC (SRS: 2(1, 4) vs 5(3, 11), TPD: (3%(1%, 5%) vs 7%(3%, 12%); z values: -4.11, -4.16, both P<0.001); all parameters measured by LEHR-SPECT and IQ-SPECT had well correlation ( r values: 0.956, 0.978, 0.958, rs values: 0.926, 0.944, all P<0.001) and consistency. Conclusions:There are good correlation and consistency of left ventricular function and myocardial perfusion parameters acquired by IQ-SPECT and LEHR-SPECT. Moreover, IQ-SPECT is able to shorten acquisition time, resulting in great potential in clinical application.
8.Pulmonary ventilation/perfusion scintigraphy in assessing residual pulmonary hypertension after pulmonary endarterectomy
Lei WANG ; Meng WANG ; Zongyao ZHANG ; Hailong ZHANG ; Wei FANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(5):257-261
Objective:To analyze the relationships between baseline percentage of pulmonary perfusion defect scores (PPDs%) and residual pulmonary hypertension after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension (CTEPH) patients.Methods:A total of 37 CTEPH patients (21 males, 16 females, age (50±12) years) who had pre- and post-pulmonary endarterectomy ventilation/perfusion (V/Q) scans from January 2016 to January 2019 at Fuwai Hospital were retrospectively collected. Residual pulmonary hypertension was defined as post-surgery mean pulmonary artery pressure (mPAP) higher than 30 mmHg (1 mmHg=0.133 kPa). Semi-quantitative index PPDs% was calculated to represent the extent of impaired perfusion in the whole lung. Pre- and post-surgery pulmonary hemodynamic parameters including pulmonary arterial pressure and resistance and lung perfusion were compared. Factors that may be related residual pulmonary hypertension were analyzed using logistic regression analysis. Paired t test and independent-sample t test were also used. Results:Pulmonary endarterectomy significantly decreased mPAP ((50.22±11.72) vs (26.41±10.61) mmHg; t=12.599, P<0.001) and pulmonary vascular resistance((10.06±5.48) vs (2.89±1.58) Wood unit; t=8.086, P<0.001). The number of defected lung segments (13.79±2.11 vs 5.52±2.82; t=11.593, P<0.001) was significantly reduced. Patients who had residual pulmonary hypertension ( n=11) exhibited significantly higher PPDs% before the surgery compared to those who were without residual pulmonary hypertension ( n=26; (57.48±5.88)% vs (47.77±11.09)%; t=-3.458, P=0.002). Baseline PPDs% was an independent factor for predicting residual pulmonary hypertension after pulmonary endarterectomy (odds ratio ( OR)=1.106, 95% CI: 1.006-1.216, P=0.036). Conclusions:Pulmonary V/Q scan can assess the therapeutic effects of pulmonary endarterectomy. Extent of impaired lung perfusion assessed by V/Q scan is the influencing factor for post-surgery residual pulmonary hypertension.
9.The value of pre-pregnancy BMI, gestational maximum fasting blood glucose and weight gain during pregnancy to evaluate fetal macrosomia after 28 weeks of gestational diabetes mellitus
Dan LI ; Haozhe SONG ; Zongyao HUANG ; Chuqi YANG ; Shijun WANG
Journal of Chinese Physician 2021;23(7):1054-1057
Objective:To analyze the relationship between pre-pregnancy body mass index (BMI), gestational random fasting glucose maximum, weight gain during pregnancy, and the occurrence of macrosomia in pregnant women diagnosed with gestational diabetes after 28 weeks gestation.Methods:The clinical data of 310 pregnant women with gestational diabetes after 28 weeks of diagnosis in Xuanwu Hospital of Capital Medical University in 2014 were retrospectively analyzed. They were divided into observation group (96 cases) with macrosomia and control group (214 cases) with normal birth weight according to the weight of newborn. The differences of BMI before pregnancy, the highest value of fasting blood glucose during pregnancy and weight gain during pregnancy between the two groups were analyzed.Results:The pre-pregnancy BMI , the highest value of random fasting blood glucose and weight gain during pregnancy in macrosomia group were significantly higher than those in non macrosomia group ( P<0.05); And the best cut-off point for predicting the delivery of macrosomia in pregnant women with gestational diabetes after 28 weeks of pregnancy was 22.077 kg/m 2, 4.965 mmol/L and 17.400 kg, respectively. The area under the curve (AUC) was 0.646, 0.595 and 0.699 respectively. After correction of confounding factors, the BMI ( OR=1.238, 95% CI: 1.132, 1.354, P<0.001) and weight gain during pregnancy ( OR=1.189, 95% CI: 1.120, 1.262, P<0.001) were risk factors for macrosomia in gestational diabetes mellitus after 28 weeks of gestation ( P<0.05). Conclusions:Pre-pregnancy BMI>22.077 kg/m 2, gestational maximum fasting blood glucose >4.965 mmol/L and gestational weight gain >17.400 kg were all high risk factors for gestational diabetes mellitus pregnant women after 28 weeks. For pregnant women with gestational diabetes, active prenatal intervention and health management are of great significance in reducing the risk of macrosomia.
10.A feasibility study of 99Tc m-MIBI/ 123I-MIBG dual-isotope cardiac imaging using CZT SPECT
Zongyao ZHANG ; Lei WANG ; Hailong ZHANG ; Kai HAN ; Wei FANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(9):536-539
Objective:To study the feasibility of cardiac 99Tc m-methoxyisobutylisonitrile (MIBI)/ 123I-metaiodobenzylguanidine (MIBG) dual-isotope imaging with cadmium-zinc-telluride (CZT) SPECT. Methods:Using a heart phantom, 99Tc m-MIBI single-isotope imaging and 99Tc m-MIBI/ 123I-MIBG dual-isotope imaging were acquired separately. Model A, B, C represented normal heart, 99Tc m/ 123I matched myocardium, 99Tc m/ 123I mismatched myocardium, respectively. Nineteen patients (9 males, 10 females; age (56±16) years) from September 2018 to June 2020 at Fuwai Hospital were enrolled to participate 99Tc m-MIBI myocardial perfusion imaging and myocardial perfusion/cardiac sympathetic imaging with 99Tc m-MIBI/ 123I-MIBG dual-isotope. Perfusion percent (PP%) and summed rest score (SRS) for all myocardial segments were obtained using quantitative perfusion SPECT (QPS) software by analyzing myocardial perfusion images. Difference and relationship between PP% and SRS were analyzed (Pearson and Spearman correlation analyses). No physical correction was applied for both acquisitions. Analysis of variance for repeated measurement data and Mann-Whitney U test were used. Results:There was no significant difference in myocardial perfusion images between 99Tc m single-isotope and 99Tc m/ 123I dual-isotope imaging with the heart phantom. 123I did not significantly impact on 99Tc m images. For patients, PP% did not differ between 99Tc m single-isotope ((69.2±14.5)%) and 99Tc m/ 123I dual-isotope imaging ((69.5±16.2)%; F=0.005, P=0.946) and correlated well ( r=0.845, P<0.01). SRS for 99Tc m single-isotope was 2(1, 13) and 2(2, 12) for 99Tc m/ 123I dual-isotope imaging ( z=-0.774, P=0.439) and the correlation between the two acquisitions was excellent ( rs=0.975, P<0.01). Conclusions:Even without physical correction, cardiac images interpretation won′t be significantly influenced by the interference of 123I with relatively higher energy on 99Tc m images. Cardiac 99Tc m-MIBI/ 123I-MIBG dual-isotope imaging is feasible.

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