Background and Aim: Low serum Vitamin D levels have been associated with diabetic nephropathy (DN). Our study aimed to analyse the serum levels of vitamin D in patients suffering from DN and the subsequent changes in serum vitamin D levels as the disease progresses.Methods: PubMed, Embase, SCOPUS and Web of Science were searched using keywords such as ‘25 hydroxyvitamin D’ and ‘diabetic nephropathy’. We included observational studies that reported the association between the serum 25 hydroxy vitamin D levels and diabetic nephropathy without restriction to age, gender, and location. R Version 4.1.2 was used to perform the meta‐analysis. The continuous outcomes were represented as mean difference (MD) and standard deviation (SD) and dichotomous outcomes as risk ratios (RR) with their 95% confidence interval (CI).Results: Twenty‐three studies were included in our analysis with 7722 patients. Our analysis revealed that vitamin D was significantly lower in diabetic patients with nephropathy than those without nephropathy (MD: −4.32, 95% CI: 7.91–0.74, p‐value = .0228). On comparing diabetic patients suffering from normoalbuminuria, microalbuminuria, or macroalbuminuria, we found a significant difference in serum vitamin D levels across different groups. Normoalbuminuria versus microalbuminuria showed a MD of −1.69 (95% CI: −2.28 to −1.10, p‐value = .0002), while microalbuminuria versus macroalbuminuria showed a MD of (3.75, 95% CI: 1.43–6.06, p‐value = .0058), proving that serum vitamin D levels keep declining as the disease progresses. Notwithstanding, we detected an insignificant association between Grade 4 and Grade 5 DN (MD: 2.29, 95% CI: −2.69–7.28, p‐value = .1862).Conclusion: Serum Vitamin D levels are lower among DN patients and keep declining as the disease progresses, suggesting its potential benefit as a prognostic marker. However, on reaching the macroalbuminuria stage (Grades 4 and 5), vitamin D is no longer a discriminating factor.

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors are commonly used drugs in the management of elevated lipid levels and cardiovascular disease. In cardiovascular diseases, among other common chronic conditions, inflammatory biomarkers are used to monitor disease progression and the risk of recurrent adverse events. We explored whether or not there was a positive effect on these biomarkers using HMG-CoA reductase inhibitors. The systematic review was conducted by gathering relevant papers mainly from three databases, identified through a generated Medical Subject Headings (MeSH) strategy. Identification of papers was subsequently followed by applying a selected inclusion and exclusion criteria to narrow the papers chosen for review. Post the application of stipulated criteria, 12 papers remained. They were subsequently assessed for risk of bias using a Cochrane risk analysis tool, identifying most as having some concerns of bias or low risk of bias. We found that HMG-CoA reductase inhibitors exhibit both a lipid-lowering effect addition to an anti-inflammatory effect.

Deficiency of fumarate hydratase (FH) protein expression in uterine corpus leiomyomas may be attributable to either germline or somatic mutations of the FH gene, the former being definitional for the hereditary leiomyomatosis and renal cell cancer syndrome. The authors assess whether, using previously reported FH-associated morphologic features, FH protein-deficient uterine corpus leiomyomas associated with a pathogenic germline mutations of the FH gene (group 1) are distinguishable from FH protein-deficient uterine corpus leiomyomas without such mutations (and whose FH protein loss is presumed to be attributable to somatic/epigenetic inactivation or other unknown phenomena: group 2). Groups 1 and 2 were compared regarding a variety of clinicopathologic features, including 7 core “FH-associated” tumoral morphologic features: staghorn vasculature; alveolar-type edema; bizarre nuclei; chain-like tumor nuclei; hyaline cytoplasmic globules; prominent nucleoli, intranuclear inclusions, and perinucleolar halos; and prominent eosinophilic/fibrillary cytoplasm. Among 2418 patients diagnosed with uterine corpus leiomyoma during the study period, FH-associated morphologic features were reported in 1.5% (37 patients), and FH immunohistochemistry was performed in 29 (1.19%). Fourteen (48.27%) of the 29 patients showed FH protein deficiency by immunohistochemistry. Twelve patients underwent germline testing, of which 8 (66.7%) were classified as group 1 and 4 (33.3%) as group 2. FH protein-deficient tumors were larger (10.44 vs 4.08 cm, P = 0.01) and associated with younger patients (42.05 vs 47.97, P = 0.004) than 370 randomly selected uterine leiomyoma controls. Groups 1 and 2 showed no significant differences in patient age and tumor size. In group 1 tumors, the FH-associated morphologic features were generally present diffusely; all group 1 tumors displayed ≥5 FH-associated features, whereas all group 2 tumors displayed <5 FH-associated features (means 6.5 ± 0.53 vs 3.5 ± 1.00, P < 0.001). Notably, eosinophilic/fibrillary cytoplasm and alveolar-type edema were each significantly more prevalent in group 1 tumors than group 2 tumors ( P = 0.018 for both). No single morphologic feature was found to be completely sensitive and specific in making the distinction between group 1 and 2 tumors. Our findings suggest that groups 1 and 2 are unlikely to be morphologically distinguishable by individual morphologic features. Whether there is a combination of features that can reliably make this distinction is unclear and will require additional studies with larger cohorts.

Next generation sequencing (NGS) is typically used to reveal tumor gene variation feature for targeted therapy of various types of human cancers, including non-small cell lung cancer (NSCLC). Here, we report the role and potential applicable value of combining DNA and RNA sequencing in gene variation detection in NSCLC. 386 NSCLC patients with stage II-IV were enrolled and detected using NGS sequencing of DNA and RNA panels that covered all well-documented target driver genes from the Chinese Society of Clinical Oncology (CSCO). The rate of epidermal growth factor receptor (EGFR) single nucleotide variation (SNV)/indel, mesenchymal-epithelial transition factor (MET) copy number variation (CNV) and anaplastic lymphoma kinase (ALK) fusion were 52.1%, 4.1% and 6.0% in the NSCLC cohort. The landscapes of SNV/indel, CNV and gene fusion in the cohort were depicted as well. Meanwhile, we assessed detection efficacy of DNA and RNA sequencing in gene fusion. Detected number and types of gene fusion using the RNA sequencing were better than those using the DNA sequencing. Gene fusion with intergenic region was only detected by DNA sequencing and MET exon 14 skipping (METΔex14) was more easily identified by RNA sequencing. Finally, we investigated clinical correlations of SNV/indel/CNV/fusion with clinicopathologic features in the NSCLC cohort. Taken together, RNA sequencing significantly complements deficiency of DNA sequencing for gene fusion, which cooperatively presents comprehensive and reliable gene variation features and facilitate the identification of potential drug targets for NSCLC patients.

Hypertrophic cardiomyopathy (HCM) is a genetically acquired disease of cardiac myocytes. Studies show that 70% of this disease is a result of different mutations in various sarcomere genes. This review aims to discuss several genetic mutations, epigenetic factors, and signal transduction pathways leading to the development of HCM. In addition, this article elaborates on recent advances in gene therapies and their implications for managing this condition. We start by discussing the founding mutations in HCM and their effect on power stroke generation. The less explored field of epigenetics including methylation, acetylation, and the role of different micro RNAs in the development of cardiac muscle hypertrophy has been highlighted in this article. The signal transduction pathways that lead to gene transcription, which in turn lead to increased protein synthesis of cardiac muscle fibers are elaborated. Finally, the microscopic events leading to the pathophysiologic macro events of cardiac failure, and the current experimental trials of gene therapy models, and the clustered regularly interspaced short palindromic repeats (CRISPR) type 2 system proteins, are discussed. We have concluded our discussion by emphasizing the need for more studies on epigenomics and experimental designs for gene therapy in HCM patients. This review focuses on the process of HCM from initial mutation to the development of phenotypic expression and various points of intervention in cardiac myocardial hypertrophy development.

Digital microscopy (DM) is one of the cutting-edge advances in pathology, which entails improved efficiency, diagnostic advantages, and potential application in virtual diagnosis, particularly in the current era of the coronavirus disease (COVID-19) pandemic. However, the diagnostic challenges are the remaining concerns for its wider adoption by pathologists, and these concerns should be addressed in a specific subspecialty. We aim to identify the common diagnostic pitfalls of whole slide imaging (WSI), one modality of DM, in gastrointestinal (GI) pathology. From validating studies of primary diagnosis performance, we included 16 records with features on GI cases involved, at least two weeks wash-out periods, and more than 60 case study designs. A tailored quality appraisal assessment was utilized to evaluate the risks of bias for these diagnostic accuracy studies. Furthermore, due to the highly heterogeneous studies and unstandardized definition of discordance, we extract the discordant cases in GI pathology and calculate the discrepant rate, resulting from 0.5% to 64.28%. Targeting discrepancy cases between digital microscopy and light microscopy, we demonstrate five main diagnostic pitfalls regarding WSI as follows: additional time to review slides in WSI, hard to identify dysplasia nucleus, missed organisms like Helicobacter pylori (H. pylori), specific cell recognitions, and technical issues. After detailed reviews and analysis, we generate two essential suggestions for further GI cases signing out by DM. One is to use systematized 20x scans for diagnostic workouts and requesting 40x or even 60x scans for challenging cases; another is that a high-volume slides training should be set before the real clinical application of WSI for primary diagnosis, particularly in GI pathology.