1.Exploring the pathogenesis of "internal heat leading to zheng" in diabetic kidney disease from the perspective of "glucose toxicity" and its differential diagnosis and treatment
Yuxin HU ; Boning CAO ; Lin WANG ; Ziheng GAO ; Maoxuan LIN ; Zeyu XUE ; Weijing LIU ; Yaoxian WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):386-391
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.
2.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.
3.Clinical Efficacy of Fuyuan Tongluo Prescription in Prevention and Treatment of Restenosis with Collateral Obstruction Syndrome After Interventional Operation of Lower Limb Arteriosclerosis Obliterans
Fangfang WU ; Xiaoyu LI ; Guobin LIU ; Hongfei WANG ; Weijing FAN ; Renyan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):134-140
ObjectiveTo observe the effects of the Fuyuan Tongluo prescription (composed of Astragali Radix, Carthami Flos, Spatholobi Caulis, Liquidambaris Fructus, Lycopodii Herba, Centellae Herba, etc.) in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans, and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group (n1=44) received dual antiplatelet therapy with aspirin and clopidogrel. The observation group (n2=44) was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate, symptom scores, ankle-brachial index (ABI), coagulation function, and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate, after 36 weeks of treatment, the observation group had a significantly better primary patency rate than the control group (χ2=4.14,P<0.05). After 24 weeks of treatment, there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison: Based on symptom quantification scores, and using the Nimodipine method as a reference, the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment (χ2=2.24,P<0.05). ABI levels: The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment (P<0.05). Coagulation function indicators: After 24 and 36 weeks of treatment, D-dimer and fibrinogen levels in both groups were lower than before treatment (P<0.05). Inflammatory markers: After 24 and 36 weeks of treatment, CRP levels in the observation group were lower than those in the control group (P<0.05). There were no significant differences in white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms, demonstrating clinical application value.
4.Clinical Efficacy of Fuyuan Tongluo Prescription in Prevention and Treatment of Restenosis with Collateral Obstruction Syndrome After Interventional Operation of Lower Limb Arteriosclerosis Obliterans
Fangfang WU ; Xiaoyu LI ; Guobin LIU ; Hongfei WANG ; Weijing FAN ; Renyan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):134-140
ObjectiveTo observe the effects of the Fuyuan Tongluo prescription (composed of Astragali Radix, Carthami Flos, Spatholobi Caulis, Liquidambaris Fructus, Lycopodii Herba, Centellae Herba, etc.) in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans, and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group (n1=44) received dual antiplatelet therapy with aspirin and clopidogrel. The observation group (n2=44) was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate, symptom scores, ankle-brachial index (ABI), coagulation function, and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate, after 36 weeks of treatment, the observation group had a significantly better primary patency rate than the control group (χ2=4.14,P<0.05). After 24 weeks of treatment, there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison: Based on symptom quantification scores, and using the Nimodipine method as a reference, the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment (χ2=2.24,P<0.05). ABI levels: The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment (P<0.05). Coagulation function indicators: After 24 and 36 weeks of treatment, D-dimer and fibrinogen levels in both groups were lower than before treatment (P<0.05). Inflammatory markers: After 24 and 36 weeks of treatment, CRP levels in the observation group were lower than those in the control group (P<0.05). There were no significant differences in white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms, demonstrating clinical application value.
5.Researches progress on the pathogenesis mechanism of ferroptosis and pharmacotherapy in kidney diseases
Weijing LAI ; Rongshuang HUANG ; Bo WANG ; Ping FU ; Liang MA
Chinese Journal of Nephrology 2024;40(5):411-417
Ferroptosis is an iron-dependent programmed cell death. Iron overload and lipid reactive oxygen accumulation play a core role in the occurrence and development of ferroptosis. Any factors affecting the balance of iron metabolism and redox system may induce and aggravate ferroptosis. Ferroptosis is involved in the pathological process of acute kidney injury, diabetic nephropathy, renal interstitial fibrosis and some other kidney diseases, and inhibiting ferroptosis has potential renoprotective benefits. This article reviewed the pathophysiological mechanism of ferroptosis and its research progress in renal diseases, and discussed the application prospect of targeted ferroptosis in the treatment of renal diseases.
6.Risk factors of recent cardiovascular and cerebrovascular events and long-term all-cause mortality in hemodialysis patients
Jiaxuan NING ; Nan YE ; Guoqin WANG ; Weijing BIAN ; Hong CHENG
Chinese Journal of Nephrology 2024;40(8):657-662
Objective:To explore the risk factors of recent cardiovascular and cerebrovascular events and long-term all-cause mortality in hemodialysis (HD) patients.Methods:The clinical data of two groups of retrospective cohort study, which included newly admitted HD (group A) and maintenance HD (group B) patients respectively, were sourced from the HD Center of Beijing Anzhen Hospital, Capital Medical University. The endpoint events were defined as occurrence of cardiovascular or cerebrovascular events or all-cause mortality at less than 12 mouths of dialysis age in group A, and all-cause mortality in group B. The patients were divided into event group and non-event group based on whether endpoint events occurred during the follow-up period. The baseline and follow-up clinical data within the two groups were compared. Cox regression model was used to analyze the risk factors of endpoint events in HD patients.Results:A total of 104 HD patients were enrolled in group A, with 70 males (67.3%), aged (61.54±14.97) years old. The follow-up time was 12.0 (10.0,12.0) months, and 29 patients (27.9%) had endpoint events. In group A, the event group had a higher proportion of peripheral arterial disease ( χ2=6.067, P=0.014), and lower low-density lipoprotein-cholesterol ( t=-2.316, P=0.023) and body mass index ( t=-2.245, P=0.028) than those in the non-event group. A total of 116 HD patients were enrolled in group B, with 86 males (74.1%), aged (65.89±10.06) years old. The follow-up time was 37.5 (21.0, 59.0) months, and 40 patients (34.5%) had endpoint events. In group B, the event group had lower serum albumin ( t=-3.182, P=0.002) and potassium ( t=-2.532, P=0.013) than those in the non-event group. Multivariate Cox regression analysis showed that high hemoglobin compliance rate ( HR=0.977, 95% CI 0.957-0.998, P=0.031) and high serum albumin ( HR=0.836, 95% CI 0.776-0.901, P<0.001) were protective factors of all-cause mortality in maintenance HD patients. Conclusions:The presence of peripheral arterial disease, low low-density lipoprotein-cholesterol and low body mass index may increase the risk of recent cardiovascular and cerebrovascular events in newly HD patients. Substandard hemoglobin and serum albumin may increase the risk of long-term all-cause mortality in maintenance HD patients.
7.Preparation of Biomimetic Dual-Mode Tumor-Targeted Nanobubbles as Ultrasound Contrast Agents and Its Function
Yu WANG ; Chao LI ; Weijing WANG ; Yunyou DUAN ; Hengli YANG
Chinese Journal of Medical Imaging 2024;32(6):533-538
Purpose To prepare biomimetic targeted nanobubbles(NBs)named IR780-RBCM@NBs and explore the ability of performing ultrasound enhancement,escaping immune surveillance and targeting tumor cells.Materials and Methods The red blood cell membrane(RBCM)was extracted from mouse blood,the IR780-RBCM@NBs were prepared by modified membrane hydration method,the physical and chemical properties of nanobubbles were detected.In vitro,self-made equipment was used to test the contrast-enhanced ultrasound imaging ability of the nanobubbles.Laser confocal fluorescence microscopy was used to observe the characteristics of the nanobubbles retaining CD47 on the RBCM surface,and further to observe the phagocytosis of the nanobubbles by macrophages and the targeting ability of the nanobubbles to different tumor cells.Results The newly prepared IR780-RBCM@NBs had the appearance of emulsion,the particle size was about(522.4±58.6)nm and the dispersity was good.It was spherical in uniform size under the microscope.IR-780 could be detected on the nanobubbles,which had the dual-mode imaging capabilities of near-infrared fluorescence imaging and contrast-enhanced ultrasound imaging.The RBCM-specific protein CD47 could be detected on the surface of the nanobubbles.The nanobubbles exhibited excellent immune phagocytic escape function and high efficiency to target different tumor cells.Conclusion Newly prepared biomimetic targeted IR780-RBCM@NBs,with good performance,can escape immune phagocytosis and efficiently target tumors,providing a new idea for molecular targeted accurate diagnosis and treatment of tumors.
8.Clinical analysis of labial mucosa graft coupled preputial island flap urethroplasty for recurrent penile curvature after hypospadias repair
Hualin CAO ; Xincheng JIANG ; Weijing YE ; Yuanyuan WANG ; Lizhuan ZHENG ; Hao WANG
Chinese Journal of Urology 2024;45(1):44-48
Objective:To investigate the clinical efficacy of labial mucosa graft coupled preputial island flap urethroplasty for recurrent penile curvature after hypospadias repair.Methods:The data of 35 patients with recurrent penile curvature after hypospadias repair who underwent labial mucosa graft coupled preputial island flap urethroplasty in four hospitals from January 2021 to March 2023 were retrospectively reviewed. The median age of the patients was 15(13, 18)years old, five of them had penile dehiscence, and four had urethrocutaneous fistula. All patients received labial mucosa graft coupled preputial island flap urethroplasty, the penile flexion was confirmed by artificial erection test, and the urethra is obliquely cut at the most obvious curvature of the penis. By removing the ventral fibrotic scar tissue, the length of the urethral defect was measured. The urethral plate was reconstructed with the same length of labial mucosa graft and an adjacent preputial island flap was transplanted to cover the reconstructed urethra plate to form a new urethral lumen. The inner urethral stent tube was extracted three days after the operation, and the outer urethral stent tube was removed three weeks after the surgery. Diagnostic urethral exploration was performed 5 weeks post-operation, uroflowmetry examination was performed seven weeks after the procedure, and the perioperative and postoperative follow-up data were analyzed.Results:All patients underwent a successful surgery, with the average duration of the procedure being (114.7±20.1)minutes. After mean follow-up of (15.5±5.9)months, no penile curvature occurred, and 32 patients were successfully repaired. Uroflowmetry examination was achieved in 21 patients at the seventh week after surgery showed their mean maximum flow rate was (18.4±3.7)ml/s. Three cases (8.6%, 3/35) developed urethrocutaneous fistula, who were repaired successfully 6 months after surgery.Conclusions:Utilizing the combination of labial mucosa grafts and preputial island flaps for urethroplasty has been proven to be a reliable and safe option for individuals with recurrent penile curvature following hypospadias repair, with a high success rate and few complications.
9.Bladder large cell lymphoma: a case report and literature review
Hao WANG ; Butang LI ; Chenfei CHI ; Xincheng JIANG ; Weijing YE ; Qi CHEN ; Guoliang YANG ; Wei XUE
Journal of Modern Urology 2024;29(2):122-125
【Objective】 To improve the understanding and diagnosis and treatment level of ALK negative anaplastic large cell lymphoma (ALK-ALCL) by sharing the diagnosis and treatment process of a patient with ALK-ALCL treated in Hangzhou Bay Hospital of Ningbo. 【Methods】 The clinical data and diagnosis and treatment process of the patient were retrospectively analyzed, and relevant literature was reviewed. 【Results】 The patient was a young male, with recurrent gross hematuria and right low back pain as the initial symptoms.Imaging examination indicated bladder tumor.After resection, the tumor was reduced and confirmed to be ALK-ALCL.After chemotherapy and autologous hematopoietic stem cell transplantation, the patient’s condition continued to improve.During the follow-up, no recurrence was observed. 【Conclusion】 Primary ALK-ALCL in the bladder is very rare and prone to misdiagnosis and missed diagnosis in clinical practice.The successful diagnosis and treatment experience of this patient can provide clinical reference.
10.Association Analysis of Serum Uric Acid and Insulin Resistance in Patients with Recurrent Spontaneous Abortion
Mei WANG ; Weijing WANG ; Fang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):739-744
Objective:To investigate the association between serum uric acid(UA)levels and insulin resistance(IR)in patients with recurrent spontaneous abortion(RSA).Methods:Using a cross-sectional design,771 pa-tients with RSA who attended the outpatient clinic of the Second Hospital of Lanzhou University from September 1,2019 to February 28,2022 were selected and classified into a hyperuricemia group(HUA)and a non-HUA group.The clinical characteristics of the two groups were compared.Univariate and multivariate Logistic regres-sion were used to analyze the influencing factors of the occurrence of IR in patients with RSA,as well asthe corre-lation between serum UA levels and IR.Related indicators were analyzed by stratified and interaction tests.Re-sults:①There were statistically significant differences(P<0.05)in the proportion of residence,BMI,triglycerides(TG),total cholesterol(TC),and high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),and related glycemic indices.②Univariate Logistic regression analysis showed that BMI,HDL-C,TG,ALT,LDL-C,and UA levels were related fac-tors affecting the occurrence of IR(P<0.05).③Multifactorial Logistic regression analysis showed that after ad-justing for all confounders(Model 2),the risk of IR increased by 4%with each 10 μmol/L increase in serum UA in patients with RSA(OR 1.04,95%Cl 1.02-1.07).Sensitivity analysis showed that in model 2,the risk of IR was significantly increased in the medium and high UA groups compared to the low UA group(OR>1,P<0.05).The results obtained from the continuous variable of serum UA were consistent with the P-value of the trend test after grouping.④Stratified analysis showed that in RSA patients with age≥30 years,BMI≥24 kg/m2,high school edu-cation or less,living in a rural area,Han ethnicity,the number of abortions≥4,higher TG and ALT values,and low-er LDL-C values and HDL-C values,the association between HUA with IR was stronger.No interaction was ob-served in the subgroups(P>0.05).Conclusions:The risk of IR increases with increasing UA levels in patients with RSA,and HUA contributes to the development of IR,especially in special populations(age≥30 years,BMI≥24 kg/m2,rural residence,number of miscarriages≥4,elevated TG and ALT,and lowered LDL-C and HDL-C).


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