Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients.

Background: The incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan. Methods: The PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation. Results: Thirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p < 0.01) had the best antihypertensive effect without significant adverse effects. Compared with valsartan 80 mg and 160 mg, valsartan 320 mg combined with hydrochlorothiazide 25 mg (p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects. Conclusions: Combination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.

Roles of Mitochondrial Dysfunction in Diabetic Kidney Disease: New Perspectives from Mechanism to Therapy.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and the main cause of end-stage renal disease around the world. Mitochondria are the main organelles responsible for producing energy in cells and are closely involved in maintaining normal organ function. Studies have found that a high-sugar environment can damage glomeruli and tubules and trigger mitochondrial dysfunction. Meanwhile, animal experiments have shown that DKD symptoms are alleviated when mitochondrial damage is targeted, suggesting that mitochondrial dysfunction is inextricably linked to the development of DKD. This article describes the mechanisms of mitochondrial dysfunction and the progression and onset of DKD. The relationship between DKD and mitochondrial dysfunction is discussed. At the same time, the progress of DKD treatment targeting mitochondrial dysfunction is summarized. We hope to provide new insights into the progress and treatment of DKD.

Validated Tools for Screening Sarcopenia: A Scoping Review.

OBJECTIVE: Choosing the optimal sarcopenia screening tool for a specific clinical scenario is challenging. We aimed to summarize all validated sarcopenia screening tools with diagnostic accuracy tested in one or more study populations. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Hospitals, nursing homes, communities, or health checkups. METHODS: We systematically searched 3 databases in April 2022: MEDLINE, EMBASE, and CENTRAL. Two review authors independently performed the study selection and data extraction. The included tools' contents, characteristics, and number of citations were summarized and visualized. RESULTS: We summarized 102 diagnostic accuracy studies involving 53 screening tools, classified into 7 groups: questionnaires (n = 13); serum biomarkers (n = 10); formulas, algorithms, and models (n = 9); physical ability tests (n = 9); integration tools (n = 7); anthropometric indices (n = 3); and ultrasound or bioimpedance analysis (n = 2). The most commonly used questionnaire was SARC-F (770 citations), followed by SARC-CalF (254 citations) and MSRA-7 (61 citations). Handgrip strength and Ishii score were the most widely used physical performance tests (331 citations) and formulas (294 citations), respectively. Sarcopenia index (based on serum cystatin C and creatinine) and calf circumference were the most commonly used serum biomarkers (123 citations) and anthropometric indexes (127 citations), respectively. Ultrasound was the most commonly used imaging tool for screening sarcopenia (57 citations). The included tools varied significantly in content. Various tools assessed some or all components of sarcopenia with different methods, and others assessed different domains, such as age, body mass index, falls, diet, and even mental health. We also summarized the screening tools that were validated in different clinical settings (hospitals, communities, nursing homes, and health checkups). CONCLUSIONS AND IMPLICATIONS: More than 50 validated tools are currently available for screening sarcopenia in different clinical settings. The results of this review may help clinicians and researchers in selecting optimal tools for sarcopenia in different clinical scenarios and in developing future tools.

HSP70 Gene Family in Brassica rapa: Genome-Wide Identification, Characterization, and Expression Patterns in Response to Heat and Cold Stress.

Heat shock proteins protect plants from abiotic stress, such as salt, drought, heat, and cold stress. HSP70 is one of the major members of the heat shock protein family. To explore the mechanism of HSP70 in Brassica rapa, we identified 28 putative HSP70 gene family members using state-of-the-art bioinformatics-based tools and methods. Based on chromosomal mapping, HSP70 genes were the most differentially distributed on chromosome A03 and the least distributed on chromosome A05. Ka/Ks analysis revealed that B. rapa evolution was subjected to intense purifying selection of the HSP70 gene family. RNA-sequencing data and expression profiling showed that heat and cold stress induced HSP70 genes. The qRT-PCR results verified that the HSP70 genes in Chinese cabbage (Brassica rapa ssp. pekinensis) are stress-inducible under both cold and heat stress. The upregulated expression pattern of these genes indicated the potential of HSP70 to mitigate environmental stress. These findings further explain the molecular mechanism underlying the responses of HSP70 to heat and cold stress.

Hypoxia-inducible factor 1α (HIF-1α) mediates the epithelial-mesenchymal transition in benign prostatic hyperplasia.

BACKGROUND: Epithelial-mesenchymal transition (EMT) based cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. It was well known that EMT markers which have been found in benign prostatic hyperplasia (BPH) tissues, but system descriptions have not been described. METHODS: First, in order to construct the epithelial cells to mesenchymal cell transformation model, BPH-1 cells were cultured with supernatant of prostate matrix normal prostate stromal WPMY-1 cells, after obtaining the culture medium through a filter. After that, we observed the morphology of cells cultured for a period of time by microscopy, detected cell invasion ability by transwell assay, detected cell proliferation ability by MTT, and detected EMT marker expression by western. Finally, we treated the cells with anti-HIF-1α drugs to study their effects on EMT, and then tested several related proteins simultaneously. RESULTS: The results showed that the morphology of BPH-1 cells gradually changed to fusiform after cultured with WSCM. At the same time, E-cadherin and cytokeratin levels were significantly lower than those in normal medium. Simultaneous detection of vimentin (SMA) and Snail was positive compared to normal cultured cells. At the same time, the cells were cultured with WSCM and the invasive ability was up-regulated. After treatment with anti-HIF-1α drug, E-cadherin and CK5/8 protein expression was up-regulated, but vimentin, α-SMA, and Snail expression was down-regulated, and in addition, p-Smad3 protein expression was also down-regulated after anti-HIF-1α drug was added. CONCLUSION: The above results indicated that WSCM-1 stromal cell supernatant WSCM can induced BPH-1 cell interstitialization, and at the same time, by inducing EMT, secreting HIF-1α activates Smad3 signaling. Our study shows that inhibition of HIF-1α expression provides a new reference for clinical treatment of BPH.

Long noncoding RNA FOXC2-AS1 facilitates the proliferation and progression of prostate cancer via targeting miR-1253/EZH2.

The vital roles of long noncoding RNAs (lncRNAs) in the cancers have been evidenced. However, there are still numerous unsolved queries for the molecular mechanism. This study tries to investigate the role of lncRNA FOXC2-AS1 in the human prostate cancer tumorigenesis. Results stated that lncRNA FOXC2-AS1 was ectopically up-regulated in prostate cancer tissue and cells. The over-expression of FOXC2-AS1 indicates the poor prognosis of prostate cancer patients. Functionally, the gain- and loss-of-functional experiments revealed that FOXC2-AS1 promoted the proliferation and tumor growth of prostate cancer cells in vitro and in vivo. Mechanically, we found that miR-1253 targeted FOXC2-AS1 at the 3'­untranslated regions (UTR), which in turn bind the EZH2 mRNA 3-UTR. Luciferase reporter assay and rescue experiment confirmed the FOXC2-AS1/miR-1253/EZH2 pathway. In conclusion, we confirmed that lncRNA FOXC2-AS1 accelerated the tumor progression of prostate cancer cells by regulating the proliferation and tumor growth through miR-1253/EZH2 axis.

Surgical Treatment for Benign Prostatic Hyperplasia: Holmium Laser Enucleation of the Prostate (HoLEP).

Benign prostatic hyperplasia (BPH) commonly occurs among elderly males. The condition causes symptoms in the lower urinary tract, thereby reducing the quality of life. BPH includes 2 major treatments: medication and surgery. Surgical treatment is often the most effective and final intervention. Holmium laser enucleation of the prostate (HoLEP), one of the most efficient surgical procedures for BPH, is conducted transurethrally. During surgery, the most important and most difficult part is to locate the surgical capsule of the prostate, which is consistent to the idea of anatomic surgery. Different skills may be needed in treating different parts of the prostate. HoLEP tends to be efficient and safe with good hemostatic properties, and able to treat bladder calculus, which may be the complications of BPH. The technique is particularly suitable for prostate of varying volumes and sizes. Indeed, HoLEP also presents certain disadvantages, such as a long learning curve and costly equipment. Regardless, this method may be the "new standard" and the excellent method for the surgical treatment of BPH.