1.Prognostic value of serum cystatin C levels on kidney outcome in type 2 diabetes mellitus patients complicated with chronic kidney disease
Fang LU ; Chengning ZHANG ; Suyan DUAN ; Yanggang YUAN ; Bo ZHANG ; Huijuan MAO ; Changying XING
Chinese Journal of Laboratory Medicine 2023;46(4):375-384
Objective:We aimed to explore the prognostic value of serum cystatin C (CysC) levels on kidney disease outcome in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD).Methods:The clinical data and pathological examination results of 113 T2DM patients with CKD, who were hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2011 to July 2020, were retrospectively analyzed in this study. Clinicopathological features and renal outcomes were compared between patients with CysC>1.54 mg/L ( n=57) and CysC≤1.54 mg/L ( n=56) at the time of renal biopsy. Cox regression analysis was used to analyze the risk factors of poor renal prognosis. The relationship between serum CysC level and renal prognosis was analyzed by smoothing curve fitting and threshold effect. Kaplan-Meier survival curve was used to compare and analyze the difference of renal survival rate. Further, the receiver operator characteristic curve was used to evaluate the predictive value of serum CysC combined with renal tubular marker blood and urinary neutrophil gelatinase-associated lipocalin (NGAL) on renal prognosis in all enrolled patients and those with different kidney disease stages. Besides, the ability of serum CysC level to predict renal prognosis within 3 years was evaluated by time-dependent area under the curve (AUC). Results:Compared with patients with serum CysC levels≤1.54 mg/L, patients with CysC>1.54 mg/L had more deteriorated renal function, decreased levels of hemoglobin and serum 25(OH) vitamin D, but more severe interstitial inflammation, higher glomerular sclerosis ratio and severe vascular lesion (all P<0.05). During 36.77 (29.34, 44.20) months follow-up, the composite renal outcomes were noted in 37.2% patients. Kaplan-Meier survival curve showed that the cumulative survival rates of patients without renal end points was significantly lower in CysC level>1.54 mg/L group than in CysC≤1.54 mg/L group (χ 2=5.752, P=0.016). Adjusted multivariate Cox analysis showed that serum CysC level ( HR=7.850, 95% CI 1.248-49.382, P<0.05) was an independent risk factor for renal prognosis. Smoothing curve fitting analysis showed that there was a linear relationship between serum CysC level and relative risk of renal endpoint event (β=2.25, 95% CI 1.06-4.81, P=0.036). The time-dependent receiver operator characteristic curve showed that the AUC of serum CysC in predicting the poor renal prognosis of T2DM patients within 3 years after renal biopsy were 0.714, 0.625 and 0.631, respectively. The AUC of serum CysC combined with blood and urinary NGAL was 0.694 (sensitivity 55.56%, specificity 77.78%). In the population with eGFR less than 60 ml·min -1·1.73m -2 ( n=51), the AUC was 0.817 (sensitivity 66.67%, specificity 85.00%). Conclusions:Higher serum CysC level is associated with deteriorated renal function, more severe renal pathological lesions and increased risk of worse renal prognosis in T2DM patients. Serum CysC level presents better predictive value for the renal prognosis of T2DM patients within 1 year after renal biopsy. Combined with renal tubular marker blood and urinary NGAL, serum CysC level might serve as a potential tool for identifying cases with high-risk of unsatisfactory renal prognosis, especially in those with eGFR less than 60 ml·min -1·1.73m -2.
2.Role of Autophagy-apoptosis Balance in Colorectal Cancer and Traditional Chinese Medicine Intervention: A Review
Mingyao XU ; Sheng XIE ; Liqun LI ; Xin LIU ; Xiaoning ZHANG ; Zhiwen SHEN ; Chengning YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):207-217
Colorectal cancer (CRC), a malignant tumor of the digestive system, originates from the colorectal mucosa epithelium and is usually asymptomatic until it progresses to an advanced stage. With high incidence around the globe and the increasingly younger patients, this disease poses a serious threat to the health and lives of the patients. Although the pathogenesis of this disease is not fully understood, it is generally believed that it is associated with autophagy, apoptosis, and inflammation. Autophagy and apoptosis as two types of programmed cell death are subject to complex interactive regulation, and the imbalance between them is closely related to the occurrence, development, and prognosis of a variety of diseases. Studies have shown that autophagy-apoptosis balance plays a key role in CRC. On the one hand, autophagy and apoptosis coordinate with each other to inhibit CRC cell growth. On the other hand, autophagy can antagonize apoptosis to promote CRC cell growth. In clinical practice, surgery is often combined with radiotherapy and chemotherapy to treat CRC, which can control the progression of CRC to a certain extent but has serious adverse effects and poor long-term results. In recent years, traditional Chinese medicine (TCM) has been proved to be effective in the treatment of CRC. Studies have shown that numerous herbal active components can promote CRC cell death by regulating the autophagy-apoptosis balance, thereby blocking the progression of this disease. The process of autophagy-apoptosis balance in regulating cell activities has similar theoretical connotations with the Yin and Yang theory of TCM. Applying TCM in regulating autophagy-apoptosis balance at various stages of CRC has become a frontier, while the comprehensive elaboration remains to be conducted. By reviewing the relevant studies in recent years, this paper introduces the correlation between the Yin and Yang theory and the autophagy-apoptosis balance, the role of autophagy-apoptosis balance in CRC, and the research progress in the application of 27 Chinese herbal active components such as flavonoids, terpenoids, glycosides, and phenols capable of regulating autophagy-apoptosis balance in the treatment of CRC. The active components in Chinese medicines can recover the autophagy-apoptosis balance in CRC by acting on microtuble-associated protein 1 light chain 3(LC3), Beclin-1, and B-cell lymphoma-2(Bcl-2)to regulate multiple signaling pathways such as protein kinase B(Akt)/mammalian target of rapamycin(mTOR)and reavtive oxygen species(ROS)/ c-Jun N-terminal kinase(JNK), thus balancing Yin and Yang. This review aims to provide a reference for the treatment of CRC and the development of new drugs.