Identification of AKI signatures and classification patterns in ccRCC based on machine learning.

Background: Acute kidney injury can be mitigated if detected early. There are limited biomarkers for predicting acute kidney injury (AKI). In this study, we used public databases with machine learning algorithms to identify novel biomarkers to predict AKI. In addition, the interaction between AKI and clear cell renal cell carcinoma (ccRCC) remain elusive. Methods: Four public AKI datasets (GSE126805, GSE139061, GSE30718, and GSE90861) treated as discovery datasets and one (GSE43974) treated as a validation dataset were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between AKI and normal kidney tissues were identified using the R package limma. Four machine learning algorithms were used to identify the novel AKI biomarkers. The correlations between the seven biomarkers and immune cells or their components were calculated using the R package ggcor. Furthermore, two distinct ccRCC subtypes with different prognoses and immune characteristics were identified and verified using seven novel biomarkers. Results: Seven robust AKI signatures were identified using the four machine learning methods. The immune infiltration analysis revealed that the numbers of activated CD4 T cells, CD56dim natural killer cells, eosinophils, mast cells, memory B cells, natural killer T cells, neutrophils, T follicular helper cells, and type 1 T helper cells were significantly higher in the AKI cluster. The nomogram for prediction of AKI risk demonstrated satisfactory discrimination with an Area Under the Curve (AUC) of 0.919 in the training set and 0.945 in the testing set. In addition, the calibration plot demonstrated few errors between the predicted and actual values. In a separate analysis, the immune components and cellular differences between the two ccRCC subtypes based on their AKI signatures were compared. Patients in the CS1 had better overall survival, progression-free survival, drug sensitivity, and survival probability. Conclusion: Our study identified seven distinct AKI-related biomarkers based on four machine learning methods and proposed a nomogram for stratified AKI risk prediction. We also confirmed that AKI signatures were valuable for predicting ccRCC prognosis. The current work not only sheds light on the early prediction of AKI, but also provides new insights into the correlation between AKI and ccRCC.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review.

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

[Shenjing Guben Pills for repairing testicular spermatogenic injury induced by oxidative stress in rats].

OBJECTIVE: To investigate the antioxidative and spermatogenesis-repairing effects of Shenjing Guben Pills (SGP), a Chinese medicine for invigorating the kidney and blood circulation, on the testis, epididymis and sperm in rats with oxidative stress injury (OSI) induced by cadmium chloride. METHODS: Seventy-two male Wistar rats were equally randomized into six groups: normal control, OSI model control, Wuzi Yanzong Pills (WYP) and low-, medium- and high-dose SGP. The OSI model was made in the latter five groups by intraperitoneal injection of cadmium chloride at 1 mg/kg, and 24 hours later, the rats of the normal and model control groups treated intragastrically with 0.9% normal saline, those of the WYP group with WYP at 4.5 g/kg/d, and those of the low-, medium- and high-dose SGP groups with SGP at 2.8, 5.6 and 11.2 g/kg/d, respectively, all for 56 days. Then, all the animals were sacrificed for obtainment of the visceral indexes and histopathological changes of the testis, epididymis and seminal vesicle, measurement of sperm concentration and motility and the percentage of morphologically normal sperm (MNS) in the epididymis, and determination of the levels of glutathione perox-idase (GSH-PX), superoxide dismutase (SOD), malondial-dehyde aldehyde (MDA) and serum testosterone (T). RESULTS: Compared with the OSI model controls, the rats in the high-, medium- and low-dose SGP groups showed significantly higher visceral indexes of the testis (ï¼»0.237 ± 0.098ï¼½ vs ï¼»0.403 ± 0.090ï¼½, ï¼»0.357 ± 0.150ï¼½ and ï¼»0.348 ± 0.140ï¼½ g/100 g, P < 0.05) and seminal vesicle (ï¼»0.241 ± 0.118ï¼½ vs ï¼»0.347 ± 0.115ï¼½, ï¼»0.336 ± 0.090ï¼½ and ï¼»0.320 ± 0.065ï¼½ g/100 g, P < 0.05) and those of the high-dose SGP group in the epididymal index (ï¼»0.099 ± 0.088ï¼½ vs ï¼»0.156 ± 0.030ï¼½ g/100 g, P < 0.05). In comparison with the OSI model controls, the animals of the high-, medium- and low-dose SGP groups exhibited significant increases in sperm concentration (ï¼»10.5 ± 17.7ï¼½ vs ï¼»58.1 ± 32.2ï¼½, ï¼»36.0 ± 36.2ï¼½ and ï¼»31.9 ± 32.7ï¼½ ×106/ml, P < 0.05) and serum T (ï¼»2.56 ± 0.75ï¼½ vs ï¼»3.62 ± 0.96ï¼½, ï¼»3.48 ± 1.33ï¼½ and ï¼»3.24 ± 0.83ï¼½ nmol/L, P < 0.05 or P < 0.01), and those of the high- and medium-dose SCG groups in total sperm motility (ï¼»9.5 ± 13.0ï¼½% vs ï¼»26.5 ± 15.5ï¼½% and ï¼»18.9 ± 8.2ï¼½%, P < 0.05) and MNS (ï¼»36.2 ± 40.2ï¼½% vs ï¼»85.3 ± 23.3ï¼½% and ï¼»65.8 ± 28.1ï¼½%, P < 0.05) and the levels GSH-PX (ï¼»3.62 ± 2.22ï¼½ vs ï¼»5.70 ± 1.73ï¼½ and ï¼»5.42 ± 2.35ï¼½ U/mg prot, P < 0.05 ) and SOD (ï¼»41.3 ± 8.8ï¼½ vs ï¼»52.7 ± 14.6ï¼½ and ï¼»51.3 ± 14.7ï¼½ U/mg prot, P < 0.05). The MDA level, however, was markedly decreased in the high-, medium- and low-dose SGP groups (ï¼»0.41 ± 0.29ï¼½, ï¼»0.44 ± 0.19ï¼½ and ï¼»0.47 ± 0.20ï¼½ nmol/mg prot) as compared with that in the OSI model controls (ï¼»0.69 ± 0.28ï¼½ nmol/mg prot) (P < 0.05). Histopathological examinations manifested coagulative necrosis, calcification and disappearance of spermatogenic and Sertoli cells in the seminiferous tubules of the OSI model controls, with decreased intraluminal secretions and atrophic epithelial papillae in the seminal vesicles and non-sperm cells in the narrowed lumens of the atrophic epididymis. With the increased dose of SGP, the proportion of normal seminiferous tubules was enlarged, the epithelia of the seminal vesicle became column-shaped again, and the epididymal lumens grew lager with more sperm cells, which indicated a dose-dependent therapeutic efficacy. Medium- and high-dose SGP achieved a significantly better effect than WYP. CONCLUSIONS: Shenjing Guben Pills can antagonize oxidative stress, elevate the levels of testicular antioxidant enzymes and serum T, repair pathological injury of the testis, epididymis and seminal vesicle, and improve semen quality and spermatogenic function.