Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes.

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Machine learning in nephrology: scratching the surface.

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

The Bone-Protecting Efficiency of Chinese Medicines Compared With Western Medicines in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Comparative Studies.

Background: Rheumatoid Arthritis (RA) is a systemic autoimmune disease leading to joint destruction. The prevention of bone and cartilage destruction has received increased attention in recent years. Objective: To evaluate the current evidences regarding the bone-protecting efficacy of Chinese medicine or the combination of Chinese medicine and Western medicine for RA. Methods: We comprehensively searched PubMed, Embase, the Cochrane Library (www.thecochranelibrary.com), the China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the two therapy methods. Results: Sixteen studies including 1,171 patients were included in the final analysis. The results showed that Chinese medicine could significantly improve the bone mineral density (BMD) (mean difference [MD] = 0.05 /g·cm-2, 95% CI [0.03, 0.08], P < 0.00001), and decrease the serum matrix metalloproteinase 3 (MMP-3) ([SMD] = -2.84, 95% CI [-4.22, -1.47], P < 0.0001). Conclusions: Chinese medicine may provide an efficiently alternative choice for the treatment of RA in terms of the bone-protecting efficiency. Given the inherent limitations of the included studies, future well-designed RCTs are required to confirm and update the findings of this analysis.

Systemic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Zhengqing Fengtongning Combined with Methotrexate in Rheumatoid Arthritis.

Chinese medicines are gaining wider acceptance. They have been used for treating rheumatoid arthritis (RA) for thousands of years, and the need to investigate the interaction between Chinese medicines and western medicines is widely recognized. In this study, a large number of RCTs and CCTs were analyzed to systematically assess the effects and adverse events of Zhengqing Fengtongning (ZQFTN) for RA. Eleven studies that contained 956 participants (508 in the treatment group; 448 in the control group) were included. The results showed that although ZQFTN combined with methotrexate MTX could not decrease the swollen joint count and tender joint count of RA patients better than MTX alone, the combination therapy might relieve the duration of morning stiffness (SMD: -16.06; 95% CI: -28.77 to -3.34), reduce laboratory indexes (RF: SMD: -10.84; 95% CI: -19.39 to -2.29; ESR: SMD: -7.26; 95% CI: -11.54 to -2.99; CRP: SMD: -3.66; 95% CI: -5.94 to -1.38), and improve the overall effect (RR: 1.08; CI: 1.01 to 1.16) better than monotherapy. The combination therapy was significantly better in controlling adverse drug reactions (RR: 0.60; 95% CI: 0.46 to 0.79). Through this systematic review, we found that ZQFTN combined with MTX for the treatment of RA might have better clinical efficacy than MTX only and might be superior in terms of controlling adverse drug reactions.

[Treatment of Refractory Rheumatoid Arthritis by Huayu Tongbi Recipe Combined Methotrexate].

OBJECTIVE: To evaluate the clinical efficacy and safety of Huayu Tongbi Recipe (HTR) combined methotrexate (MTX) in treating refractory rheumatoid arthritis (RRA). METHODS: Totally 167 RRA patients were assigned to the treatment group (73 cases) and the control group (94 cases) according to different therapeutic methods. Patients in the treatment group were treated with HTR combined MTX, while those in the control group were treated with leflunomide (LEF) combined MTX. Clinical signs and symptoms, RF, CRP, ESR, disease activity score 28 (DAS28), and safety indicators were compared between the two groups before treatment, at week 12 and 24 after treatment. The efficacy and safety indices were also evaluated. RESULTS: At week 12 after treatment the total effective rate was 82.2% (60/73 cases) in the treatment group and 79.8% (75/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). At week 24 after treatment the total effective rate was 78.1% (57/73 cases) in the treatment group and 755% (71/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). There was statistical difference in the total effective rate between week 24 and week 12 in the control group (chi2 = 0.49, P < 0.05). Clinical signs and symptoms, RF, CRP, ESR, and DAS28 were significantly improved in the two groups after 12- and 24-week treatment (P < 0.01). There was no statistical difference in the improvement at week 12 after treatment between the two groups (P > 0.05). There was statistical difference in time of morning stiffness, tender joint numbers, swollen joint numbers, patient global assessment, RF, CRP, and DAS28 at week 24 after treatment between the two groups (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.01). CONCLUSION: The efficacy of HTR combined MTX was equivalent to that of LEF (10 mg per day) combined MTX, but with more stable therapeutic effects and less adverse reactions.