1.Effect of Shenkang Injection on Podocyte Apoptosis and GRP78/CHOP Signaling Pathway in db/db Mice with Diabetic Kidney Disease Based on Endoplasmic Reticulum Stress
Yanmo CAI ; Sitong WANG ; Xin ZHOU ; Ge JIN ; Kaidong ZHOU ; Yunhua LIU ; Fengfeng ZHANG ; Xinxue ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):81-90
ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 ( GRP78 ) / transcription factor C / EBP homologous protein ( CHOP ) signaling pathway (GRP78/CHOP) signaling pathway. MethodsFor the animal experiment, 10 12-week-old db/m mice were selected as a normal group, and 30 12-week-old db/db mice were randomly divided into a model group, a Shenkang injection group (15.6 mL·kg-1), and a dapagliflozin group (1.6 mg·kg-1). To observe the general condition of mice, fasting blood glucose, urinary albumin/urine creatinine (ACR), and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment, mice were tested for fasting blood glucose, total cholesterol (TC), triglyceride (TG), low-density cholesterol (LDL), ACR, 24 h urine protein quantification, blood creatinine (SCr), and blood urea (UREA). Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein (Nephrin), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in renal tissue. Western blot was used to detect the expressions of GRP78, CHOP, Bcl-2, Bax, and Nephrin proteins, and Real-time polymerase chain reaction (Real-time PCR) was employed to detect the expressions of Nephrin, GRP78, CHOP, Bcl-2, and Bax mRNAs in renal tissue. ResultsBefore drug administration, compared with those in the normal group, the body mass of db/db mice was significantly increased, and blood glucose, 24 h urine protein quantification, and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group (P<0.01). After 12 weeks of administration, compared with those in the model group, the general state of mice in the Shenkang injection group was significantly improved, and the body mass was decreased. The blood glucose was significantly reduced (P<0.01), and blood lipids TC, TG, and LDL were significantly decreased (P<0.05, P<0.01). The 24 h urine protein quantification and ACR were significantly decreased (P<0.05), and SCr and UREA were significantly reduced (P<0.01). Compared with those of the model group, the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells, reduction of inflammatory cell infiltration, and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78, CHOP, and Bax proteins were significantly reduced (P<0.01), and the expressions of Nephrin and Bcl-2 proteins were significantly increased (P<0.01) in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased (P<0.05, P<0.01), and the expressions of GRP78, CHOP, and Bax proteins were significantly decreased (P<0.05, P<0.01). Real-time PCR results showed that the expressions of GRP78, CHOP, and Bax mRNAs were down regulated in the Shenkang injection group (P<0.01), and the expressions of Nephrin and Bcl-2 mRNAs were up regulated (P<0.01). ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway, which in turn ensures the integrity of glomerular filtration barrier, reduces the occurrence of proteinuria, improves renal function, and thus delays the progression of diabetic kidney disease.
2.Effect of Shenkang Injection on Podocyte Apoptosis and GRP78/CHOP Signaling Pathway in db/db Mice with Diabetic Kidney Disease Based on Endoplasmic Reticulum Stress
Yanmo CAI ; Sitong WANG ; Xin ZHOU ; Ge JIN ; Kaidong ZHOU ; Yunhua LIU ; Fengfeng ZHANG ; Xinxue ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):81-90
ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 ( GRP78 ) / transcription factor C / EBP homologous protein ( CHOP ) signaling pathway (GRP78/CHOP) signaling pathway. MethodsFor the animal experiment, 10 12-week-old db/m mice were selected as a normal group, and 30 12-week-old db/db mice were randomly divided into a model group, a Shenkang injection group (15.6 mL·kg-1), and a dapagliflozin group (1.6 mg·kg-1). To observe the general condition of mice, fasting blood glucose, urinary albumin/urine creatinine (ACR), and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment, mice were tested for fasting blood glucose, total cholesterol (TC), triglyceride (TG), low-density cholesterol (LDL), ACR, 24 h urine protein quantification, blood creatinine (SCr), and blood urea (UREA). Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein (Nephrin), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in renal tissue. Western blot was used to detect the expressions of GRP78, CHOP, Bcl-2, Bax, and Nephrin proteins, and Real-time polymerase chain reaction (Real-time PCR) was employed to detect the expressions of Nephrin, GRP78, CHOP, Bcl-2, and Bax mRNAs in renal tissue. ResultsBefore drug administration, compared with those in the normal group, the body mass of db/db mice was significantly increased, and blood glucose, 24 h urine protein quantification, and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group (P<0.01). After 12 weeks of administration, compared with those in the model group, the general state of mice in the Shenkang injection group was significantly improved, and the body mass was decreased. The blood glucose was significantly reduced (P<0.01), and blood lipids TC, TG, and LDL were significantly decreased (P<0.05, P<0.01). The 24 h urine protein quantification and ACR were significantly decreased (P<0.05), and SCr and UREA were significantly reduced (P<0.01). Compared with those of the model group, the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells, reduction of inflammatory cell infiltration, and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78, CHOP, and Bax proteins were significantly reduced (P<0.01), and the expressions of Nephrin and Bcl-2 proteins were significantly increased (P<0.01) in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased (P<0.05, P<0.01), and the expressions of GRP78, CHOP, and Bax proteins were significantly decreased (P<0.05, P<0.01). Real-time PCR results showed that the expressions of GRP78, CHOP, and Bax mRNAs were down regulated in the Shenkang injection group (P<0.01), and the expressions of Nephrin and Bcl-2 mRNAs were up regulated (P<0.01). ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway, which in turn ensures the integrity of glomerular filtration barrier, reduces the occurrence of proteinuria, improves renal function, and thus delays the progression of diabetic kidney disease.
3.Yishen Huashi Granules Protect Kidneys of db/db Mice via p38 MAPK Signaling Pathway
Kaidong ZHOU ; Sitong WANG ; Ge JIN ; Yanmo CAI ; Xin ZHOU ; Yunhua LIU ; Xinxue ZHANG ; Min ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):58-68
ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model , dapagliflozin (1.6 mg·kg-1), and Yishen Huashi granules (4.7 g·kg-1), and db/m mice were used as the control group. The general conditions of mice were observed, and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio (ACR) were measured at weeks 0 and 12 of administration. After 12 weeks of treatment, the levels of serum creatinine (SCr), blood urea (UREA), triglycerides (TG), total cholesterol (TC), and low density lipoprotein (LDL) were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin (HE) staining, Periodic acid-Schiff (PAS) staining, Mallory staining, and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor-2 (CCR2) in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38, phospho-p38 (p-p38), MCP-1, and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38, p38, MCP-1, and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows: negative control, high glucose(30 mmol·L-1), Yishen Huashi granule-containing serum, and SB203580. After 48 h of cell culture in each group, RNA were extracted and the levels of MCP-1, and CCR2 mRNA were determined by Real-time PCR,proteins were extracted and the levels of p38, p-p38, MCP-1, and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment, other groups had higher body weight, blood glucose level, 24 h urinary protein, and ACR than the control group (P<0.05,P<0.01). After 12 weeks of treatment, compared with the model group, the Yishen Huashi granules group showed improved general conditions, a decreasing trend in body weight, lowered levels of blood glucose, 24-h urinary protein, and ACR (P<0.01), reduced SCr and UREA (P<0.01), and declined levels of TC, TG, and LDL (P<0.05,P<0.01). Compared with the model group, the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover, the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 (P<0.01), reduced positive expression of p-p38, MCP-1, and CCR2 (P<0.01), and down-regulated protein levels of p-p38/p38, MCP-1, and CCR2 (P<0.05) in the renal tissue. The cell experiment showed that compared with the high glucose group, the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 (P<0.01) and down-regulated protein levels of p-p38/p38, MCP-1, and CCR2(P<0.05,P<0.01). ConclusionYishen Huashi granules can regulate glucose-lipid metabolism, reduce 24 h urinary protein and ACR, improve the renal function, alleviate the renal tubule injury caused by high glucose, and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.
4.Application of CXCR4-targeted PET/CT imaging in the classification and precise localization of primary aldosteronism
Xuan YIN ; Xiaowei MA ; Chuning DONG ; Lianbo ZHOU ; Rongchen AN ; Honghui GUO ; Xin XIANG ; Xinlu ZHANG ; Hong XIANG ; Yunhua WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):76-81
Objective:To investigate the application value of 68Ga-Pentixafor PET/CT targeting CXC subfamily receptor 4 (CXCR4) in the subtyping and precise localization of primary aldosteronism (PA). Methods:Thirty-three patients with PA confirmed by clinical examination and undergoing 68Ga-Pentixafor PET/CT and adrenal vein sampling (AVS) in the Second Xiangya Hospital between July 1st 2022 and July 1st 2023 were prospectively enrolled (24 males, 9 females, age (49.6±10.3) years). Patients with a dominant side identified by PET/CT or AVS underwent unilateral adrenalectomy, while those without a dominant side received medical treatment. According to the standard of PA surgical outcome (PASO), patients underwent surgery were divided into unilateral PA (UPA) and bilateral PA (BPA) based on the pathological and follow-up results. Those who received medical treatment were BPA. The diagnostic efficacy of 68Ga-Pentixafor PET/CT for UPA was calculated. The ROC curve was constructed to analyze the accuracy and optimal threshold of SUV max, the ratio of lesion SUV max to contralateral adrenal tissue SUV mean (LCR), and the ratio of lesion SUV max to liver SUV mean (LLR) in the diagnosis of PA subtype. The correlation between the quantitative parameters and the clinical features and lesion width of the patients was evaluated by Spearman rank correlation analysis. The differences of LCR and LLR between different efficacy groups were compared by the independent-sample t test. Results:A total of 20 patients underwent unilateral adrenalectomy. Nineteen patients were finally diagnosed with UPA and 14 with BPA. The agreement rate of PET/CT and AVS was 81.8%(27/33), and both methods independently detected UPA that was negative in the other examination. The sensitivity, specificity, and accuracy of 68Ga-Pentixafor PET/CT visual diagnosis of UPA were 18/19, 14/14, and 97.0%(32/33), respectively. ROC curve showed that the AUC of LLR for subtype diagnosis was 0.944, with the optimal threshold of 3.1. SUV max, LCR, and LLR were positively correlated with aldosterone concentration ( rs values: 0.35, 0.47, and 0.36, all P<0.05) and lesion width ( rs values: 0.43, 0.49, and 0.58, all P<0.05). The LCR (3.9±2.2 vs 1.6±0.3; t=2.00, P=0.041) and LLR( 8.7±4.1 vs 4.2±1.3; t=2.06, P=0.045) of the dominant side lesions in patients who achieved complete biochemical and clinical cure were higher than those in patients with partial improvement. Conclusions:68Ga-Pentixafor PET/CT imaging can be used in the diagnosis and precise localization of PA subtype. It also can detect patients with PA which can be surgically cured but not detected by AVS, and the quantitative analysis may be valuable for prognosis prediction.
5.Application and effectiveness evaluation of the"cloud-based PAD class"blended teaching model in on-line clinical clerkship teaching of palliative oncology
Xueqin LI ; Hui DONG ; Lijuan ZHANG ; Quan GONG ; Chunyan ZHOU ; Jun LI ; Jiaxin WANG ; Yunhua WANG
Modern Hospital 2025;25(10):1623-1627
Objective To evaluate the effectiveness of a blended teaching model integrating the HBOPPPS framework(Hybrid Bridge-in,Objectives,Pre-assessment,Participatory learning,Post-assessment,Summary)and the"Cloud-based PAD Class"(Presentation-Assimilation-Discussion)in online clinical clerkship teaching for palliative oncology.Methods A self-con-trolled trial was conducted in October 2023,involving 41 undergraduate students majoring in Food Hygiene and Nutrition(Grade 2021)from Kunming Medical University.Phase 1 implemented conventional online teaching(control group),while Phase 2 adopted the"HBOPPPS+Cloud-based PAD Class"blended approach(experimental group).Teaching effectiveness was assessed via post-class examination scores,classroom participation rates,and satisfaction surveys.Results The experimental group dem-onstrated significantly higher outcomes than the control group:examination scores(86.34±4.19 vs.80.02±3.63,P<0.05),classroom participation(51.2%vs.12.2%,P<0.05),and teaching satisfaction(95.1%vs.80.5%,P<0.05).Conclu-sionThe"HBOPPPS+Cloud-based PAD Class"blended teaching model effectively enhances online clinical clerkship outcomes in palliative oncology,significantly improving students' learning initiative,engagement,and classroom participation.
6.Application of CXCR4-targeted PET/CT imaging in the classification and precise localization of primary aldosteronism
Xuan YIN ; Xiaowei MA ; Chuning DONG ; Lianbo ZHOU ; Rongchen AN ; Honghui GUO ; Xin XIANG ; Xinlu ZHANG ; Hong XIANG ; Yunhua WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):76-81
Objective:To investigate the application value of 68Ga-Pentixafor PET/CT targeting CXC subfamily receptor 4 (CXCR4) in the subtyping and precise localization of primary aldosteronism (PA). Methods:Thirty-three patients with PA confirmed by clinical examination and undergoing 68Ga-Pentixafor PET/CT and adrenal vein sampling (AVS) in the Second Xiangya Hospital between July 1st 2022 and July 1st 2023 were prospectively enrolled (24 males, 9 females, age (49.6±10.3) years). Patients with a dominant side identified by PET/CT or AVS underwent unilateral adrenalectomy, while those without a dominant side received medical treatment. According to the standard of PA surgical outcome (PASO), patients underwent surgery were divided into unilateral PA (UPA) and bilateral PA (BPA) based on the pathological and follow-up results. Those who received medical treatment were BPA. The diagnostic efficacy of 68Ga-Pentixafor PET/CT for UPA was calculated. The ROC curve was constructed to analyze the accuracy and optimal threshold of SUV max, the ratio of lesion SUV max to contralateral adrenal tissue SUV mean (LCR), and the ratio of lesion SUV max to liver SUV mean (LLR) in the diagnosis of PA subtype. The correlation between the quantitative parameters and the clinical features and lesion width of the patients was evaluated by Spearman rank correlation analysis. The differences of LCR and LLR between different efficacy groups were compared by the independent-sample t test. Results:A total of 20 patients underwent unilateral adrenalectomy. Nineteen patients were finally diagnosed with UPA and 14 with BPA. The agreement rate of PET/CT and AVS was 81.8%(27/33), and both methods independently detected UPA that was negative in the other examination. The sensitivity, specificity, and accuracy of 68Ga-Pentixafor PET/CT visual diagnosis of UPA were 18/19, 14/14, and 97.0%(32/33), respectively. ROC curve showed that the AUC of LLR for subtype diagnosis was 0.944, with the optimal threshold of 3.1. SUV max, LCR, and LLR were positively correlated with aldosterone concentration ( rs values: 0.35, 0.47, and 0.36, all P<0.05) and lesion width ( rs values: 0.43, 0.49, and 0.58, all P<0.05). The LCR (3.9±2.2 vs 1.6±0.3; t=2.00, P=0.041) and LLR( 8.7±4.1 vs 4.2±1.3; t=2.06, P=0.045) of the dominant side lesions in patients who achieved complete biochemical and clinical cure were higher than those in patients with partial improvement. Conclusions:68Ga-Pentixafor PET/CT imaging can be used in the diagnosis and precise localization of PA subtype. It also can detect patients with PA which can be surgically cured but not detected by AVS, and the quantitative analysis may be valuable for prognosis prediction.
7.Application and effectiveness evaluation of the"cloud-based PAD class"blended teaching model in on-line clinical clerkship teaching of palliative oncology
Xueqin LI ; Hui DONG ; Lijuan ZHANG ; Quan GONG ; Chunyan ZHOU ; Jun LI ; Jiaxin WANG ; Yunhua WANG
Modern Hospital 2025;25(10):1623-1627
Objective To evaluate the effectiveness of a blended teaching model integrating the HBOPPPS framework(Hybrid Bridge-in,Objectives,Pre-assessment,Participatory learning,Post-assessment,Summary)and the"Cloud-based PAD Class"(Presentation-Assimilation-Discussion)in online clinical clerkship teaching for palliative oncology.Methods A self-con-trolled trial was conducted in October 2023,involving 41 undergraduate students majoring in Food Hygiene and Nutrition(Grade 2021)from Kunming Medical University.Phase 1 implemented conventional online teaching(control group),while Phase 2 adopted the"HBOPPPS+Cloud-based PAD Class"blended approach(experimental group).Teaching effectiveness was assessed via post-class examination scores,classroom participation rates,and satisfaction surveys.Results The experimental group dem-onstrated significantly higher outcomes than the control group:examination scores(86.34±4.19 vs.80.02±3.63,P<0.05),classroom participation(51.2%vs.12.2%,P<0.05),and teaching satisfaction(95.1%vs.80.5%,P<0.05).Conclu-sionThe"HBOPPPS+Cloud-based PAD Class"blended teaching model effectively enhances online clinical clerkship outcomes in palliative oncology,significantly improving students' learning initiative,engagement,and classroom participation.
8.Prognostic values of 18F-FDG PET/CT metabolic parameters combined with clinical pathological indicators in cutaneous malignant melanoma
Rongchen AN ; Yunhua WANG ; Xinyu LU ; Lianbo ZHOU ; Xiaowei MA ; Chuning DONG ; Xin XIANG ; Xuan YIN ; Honghui GUO ; Jiaying YUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):396-400
Objective:To discuss the relationship between 18F-FDG PET/CT metabolic parameters and clinical pathological indicators and prognosis in cutaneous malignant melanoma (CMM). Methods:A total of 100 CMM patients (62 males, 38 females, age (56.5±2.5) years) who underwent 18F-FDG PET/CT scans at the Second Xiangya Hospital of Central South University from August 2013 to November 2022 were retrospectively enrolled. Clinical pathological indicators (such as primary site, TNM staging, sentinel lymph node (SLN) status) and metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), whole-body MTV (wb-MTV), and whole-body TLG (wb-TLG)) were collected. ROC curve analyses were used to determine the PET parameters thresholds for progression-free survival (PFS) and melanoma-specific survival (MSS). Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards regression models were used to analyze the prognosis of patients′ PFS and MSS, and a nomogram survival prediction model was constructed. Results:Results of ROC curve analyses showed that the thresholds of SUV max of primary tumor (p-SUV max), MTV of primary tumor (p-MTV), TLG of primary tumor (p-TLG), wb-MTV and wb-TLG for predicting PFS and MSS were 7.13, 2.24 cm 3, 6.98 g, 2.57 cm 3, 8.04 g and 9.09, 2.34 cm 3, 7.44 g, 2.24 cm 3, 9.17 g, respectively. Results of univariate analysis indicated that several clinical pathological indicators and metabolic parameters were prognostic risk factors for PFS and MSS. Results of multivariate analysis indicated that metastases of SLN (hazard ratio( HR)=2.54, 95% CI: 1.09-5.90; P=0.030) and wb-TLG>8.04 g( HR=2.58, 95% CI: 1.17-5.72; P=0.019) were independent prognostic risk factors for PFS, while metastases of SLN ( HR=4.53, 95% CI: 1.54-13.35; P=0.006) and wb-TLG>9.17 g ( HR=2.48, 95% CI: 1.26-4.89; P=0.009) were independent risk prognostic factors for MSS. A nomogram survival prediction model based on PET metabolic parameter (wb-TLG) and clinical pathological indicator (SLN status) can effectively predict the prognosis of CMM patients. Conclusions:Clinical pathological parameters and PET parameters are associated with the prognosis of CMM patients. SLN status is critical for prognosis.
9.Evolution Patterns of 256 Cases of Chronic Kidney Disease with Kidney Yang Deficiency Syndrome Based on Data Mining
Xinjiang ZHANG ; Xinxue ZHANG ; Zuzhen YAN ; Yunhua LIU ; Shuyue WANG ; Sitong WANG ; Kaidong ZHOU ; Zongjiang ZHAO ; Yan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):141-150
ObjectiveTo analyze the characteristics of kidney Yang deficiency syndrome in different stages and time evolution of chronic kidney disease (CKD) to explore the evolution patterns of kidney Yang deficiency syndrome in CKD. MethodThe evidence information of 256 patients with CKD was collected from October 2020 to September 2022 according to relevant standards, and the "Kidney Yang Deficiency Syndrome Evaluation Scale for Chronic Kidney Disease" was developed. With SPSS Statistics 20.0, SPSS Modeler 18.0, Gephi 0.9.2, and R 4.2.1, the syndrome information of CKD patients at various stages and the syndrome changes after one year were statistically analyzed using complex network analysis, association rule analysis, probability transition matrix analysis, and chi-square test, and the kidney Yang deficiency syndrome of patients at various stages was comprehensively evaluated. ResultIn the CKD population, the proportion of females with kidney Yang deficiency syndrome was higher than that of males (P<0.01), and the proportion of people over 65 years old was higher than in people under 65 years old. The proportion of people with kidney Yang deficiency syndrome increased with the progression of kidney disease, and the proportion of Ⅳ-Ⅴ CKD patients with kidney Yang deficiency syndrome was higher than that of Ⅰ-Ⅱ CKD patients (P<0.01). From Ⅰ CKD to Ⅴ CKD, the frequency of dull tongue continued to increase, and the frequency of enlarged tongue and tooth-marked tongue continued to increase after Ⅲ CKD. The frequency of thick coating and greasy coating ranked in the top 3 of frequency distribution in Ⅴ CKD. After Ⅲ CKD, the top 3 tongue characteristics were weak pulse, deep pulse, and thready pulse, all of which were characteristics of kidney Yang deficiency syndrome. Complex network analysis of the tongue and pulse showed that the core tongue and pulse characteristics of patients with end-stage CKD were tooth-marked tongue with white coating and deep and thready pulse. The results of symptom frequency analysis and complex network analysis showed that aversion to cold and preference for warmth, weakness of the knees, and cold extremities were the top 3 symptoms in Ⅰ-Ⅲ CKD patients with kidney Yang deficiency syndrome, and in Ⅳ-Ⅴ CKD, the manifestations of the syndrome of Yang deficiency and water diffusion, such as drowsiness and fatigue, edema, and frequent urination at night became characteristic symptoms. The scores of edema, pale complexion, soreness and weakness of the waist and knees, loose stools, and mental depression symptoms, as well as the total score of kidney Yang deficiency syndrome gradually increased with disease progression, with statistical differences between different stages of CKD (P<0.05, P<0.01). The frequency analysis of disease-related syndrome elements showed that the frequencies of Yang deficiency syndrome, phlegm-dampness syndrome, blood stasis syndrome, and turbidity-toxin syndrome gradually increased with disease progression, and there were statistically significant differences in the distribution between different stages of CKD (P<0.05, P<0.01). The results of complex network analysis showed that Yang deficiency syndrome was the core syndrome element throughout all stages of CKD and was the main syndrome element type of CKD, while phlegm-dampness syndrome, blood stasis syndrome, and turbidity-toxin syndrome were gradually revealed in the middle and late stages of CKD. In the CKD population with kidney-Yang deficiency syndrome, the distribution of phlegm-dampness syndrome, blood stasis syndrome, and turbidity-toxin syndrome as concurrent syndromes in different CKD stages had statistically significant differences (P<0.05, P<0.01). The association rule analysis showed that as the disease progressed, associations between the concurrent syndromes, such as phlegm-dampness syndrome, blood stasis syndrome, turbidity-toxin syndrome, and fluid retention syndrome, and kidney-Yang deficiency syndrome were gradually enhanced. The comparison of the changes in CKD with kidney Yang deficiency syndrome within one year showed that the disease location was centered on the kidney and transmitted between the spleen, stomach, heart, and liver. There is a 23.81% probability of kidney-Yang deficiency syndrome transforming into Qi deficiency syndromes (Qi deficiency in the spleen and kidney, Qi deficiency in the liver, and Qi deficiency in the heart), 23.79% into Yin deficiency syndromes (Yin deficiency in the liver and kidney, Qi and Yin deficiency, and Yin deficiency in the liver and stomach), and 9.52% into dampness syndromes (phlegm-dampness internal obstruction and wind-dampness obstruction). In contrast, 20% of spleen and kidney Qi deficiency syndrome transformed into kidney Yang deficiency syndrome, and 33.33% of Qi deficiency and blood stasis syndrome transformed into kidney Yang deficiency syndrome. ConclusionAs Ⅰ CKD progresses to Ⅴ CKD, the severity of kidney Yang deficiency syndrome gradually increases, and the syndrome characteristics of kidney Yang deficiency become pronounced. Furthermore, the pathogenic factors, such as phlegm-dampness, blood stasis, and turbidity-toxin, gradually increase. With the change of time, kidney Yang deficiency syndrome in CKD tends to evolve into syndromes related to Qi deficiency, Yin deficiency, and dampness. The discovery of these rules provides a theoretical basis and reference guidance for the treatment of CKD based on syndrome differentiation.
10.Quantitative Analysis of Syndromes in 558 Cases of Kidney Yang Deficiency Syndrome Based on Factor Analysis
Shuyue WANG ; Zongjiang ZHAO ; Xinxue ZHANG ; Zuzhen YAN ; Yan ZHANG ; Zhimei ZHANG ; Tingting JIAO ; Qi WU ; Yunhua LIU ; Sitong WANG ; Xinjiang ZHANG ; Kaidong ZHOU
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(7):2304-2312
Objective Through factor analysis of the quantified syndrome information of 558 cases of kidney yang deficiency syndrome,the constructing feature of kidney yang deficiency syndrome was revealed,which provides clinical data support for the objectification,standardization and normalization of kidney Yang deficiency syndrome.Methods Firstly,the frequency analysis of symptoms,tongue and pulse signs of 558 patients with kidney Yang deficiency syndrome was carried out,and then the main syndrome information of the patients with kidney Yang deficiency syndrome was quantified.Finally,the common factors and their representative variables of kidney Yang deficiency syndrome were screened out through factor analysis,and the constructing feature of kidney Yang deficiency syndrome was analyzed combined with TCM syndrome knowledge.Results Eight common factors with eigenvalues greater than 1 were extracted by principal component analysis,and the cumulative contribution rate was 60.483%.After the factor rotation,the representative variables with the absolute value of load coefficient greater than 0.45 in each common factor were selected.The representative variables of F1 are afraid of cold and fond of warmth(0.947)and intolerance to cold(0.932).The representative variables of F2 are waist pain(0.754),waist and knee weakness(0.720)and cold in waist and knees(0.466).The representative variables of F3 are depression(0.749),insomnia(0.711)and diarrhoea(0.470).The representative variables of F4 are thin fur(0.819)and white fur(0.768).The representative variable of F5 are tinnitus and deafness(0.687),frequent nocturnal urination(0.591)and decreased libido(0.587).The representative variables of F6 are pulse sinking(0.766)and pulse weakness(0.736).The representative variables of F7 is thready pulse(0.942).The representative variable of F8 is pale tongue(0.961).External syndrome of disease location involved in these common factors are waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.The disease nature involved in these common factors is deficiency and cold.Conclusion The basic constituent units of kidney Yang deficiency syndrome include disease location syndrome elements and disease nature syndrome elements.The disease location is kidney,and the abnormal changes of kidney location are mainly external symptoms of waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.Its disease nature is deficiency and cold.Yang deficiency leads to external cold.Yang Qi deficiency can not warm the body surface resulting in the appearance of external cold syndrome.

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