Precise GDP Spatialization and Analysis in Built-Up Area by Combining the NPP-VIIRS-like Dataset and Sentinel-2 Images.

Spatialization and analysis of the gross domestic product of second and tertiary industries (GDP23) can effectively depict the socioeconomic status of regional development. However, existing studies mainly conduct GDP spatialization using nighttime light data; few studies specifically concentrated on the spatialization and analysis of GDP23 in a built-up area by combining multi-source remote sensing images. In this study, the NPP-VIIRS-like dataset and Sentinel-2 multi-spectral remote sensing images in six years were combined to precisely spatialize and analyze the variation patterns of the GDP23 in the built-up area of Zibo city, China. Sentinel-2 images and the random forest (RF) classification method based on PIE-Engine cloud platform were employed to extract built-up areas, in which the NPP-VIIRS-like dataset and comprehensive nighttime light index were used to indicate the nighttime light magnitudes to construct models to spatialize GDP23 and analyze their change patterns during the study period. The results found that (1) the RF classification method can accurately extract the built-up area with an overall accuracy higher than 0.90; the change patterns of built-up areas varied among districts and counties, with Yiyuan county being the only administrative region with an annual expansion rate of more than 1%. (2) The comprehensive nighttime light index is a viable indicator of GDP23 in the built-up area; the fitted model exhibited an R2 value of 0.82, and the overall relative errors of simulated GDP23 and statistical GDP23 were below 1%. (3) The year 2018 marked a significant turning point in the trajectory of GDP23 development in the study area; in 2018, Zhoucun district had the largest decrease in GDP23 at -52.36%. (4) GDP23 gradation results found that Zhangdian district exhibited the highest proportion of high GDP23 (>9%), while the proportions of low GDP23 regions in the remaining seven districts and counties all exceeded 60%. The innovation of this study is that the GDP23 in built-up areas were first precisely spatialized and analyzed using the NPP-VIIRS-like dataset and Sentinel-2 images. The findings of this study can serve as references for formulating improved city planning strategies and sustainable development policies.

Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

BACKGROUND: Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status. METHODS: In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height. RESULTS: Of 202 MEC patients, most were male (166/82%), < 65 years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9 months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1-2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%). CONCLUSIONS: In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures.

Research progress of sirtuins in renal and cardiovascular diseases.

PURPOSE OF REVIEW: Sirtuins are a family of nicotinamide adenine dinucleotide+-dependent enzymes catalyzing target protein deacetylation to modulate cellular metabolism, response to oxidative stress and inflammation, senescence, autophagy and apoptosis. In this review, we provide an overview of recent studies regarding the alterations and roles of sirtuins in a variety of renal and cardiovascular diseases. We are also going to highlight activators and inhibitors of sirtuins in the prevention of these diseases. This will help us to understand how this field may change in the future. RECENT FINDING: Recent studies have elucidated how physical or diseased conditions alter the expressions and enzyme activity of sirtuins and expounded sexual differences in sirtuins functions. In addition, interventions by targeting sirtuins have been applied in preclinical and clinical studies to prevent or slow the development of related diseases. SUMMARY: The advantages of female sex in renal and cardiovascular diseases are partially due to the expression and function of sirtuins. Estrogen activates sirtuins and in turn sirtuins promote estrogen receptor signaling. In addition, the hypoglycemic agents, sodium-glucose cotransporter 2 inhibitors protect against diabetic nephropathy at least in part via activating SIRT-1. Although several compounds targeted sirtuins are promising drug candidates in a variety of renal and cardiovascular diseases, well designed large clinical trials are still required to identify their efficacy and safety.

Protection against diabetic cardiomyopathy is achieved using a combination of sulforaphane and zinc in type 1 diabetic OVE26 mice.

Sulforaphane (SFN) can effectively induce nuclear factor E2-related factor 2 (Nrf2), and zinc (Zn) can effectively induce metallothionein (MT), both of which have been shown to protect against diabetic cardiomyopathy (DCM). However, it is unclear whether combined treatment with SFN and Zn offers better cardiac protection than either one alone. Here, we treated 5-week-old OVE mice that spontaneously develop type 1 diabetes with SFN and/or Zn for 18 weeks. Cardiac dysfunction, by echocardiography, and pathological alterations and remodelling, shown by cardiac hypertrophy, fibrosis, inflammation and oxidative damage, examined by histopathology, Western blotting and real-time PCR, were observed in OVE mice. All these dysfunction and pathological abnormalities seen in OVE mice were attenuated in OVE mice with treatment of either SFN, Zn or SFN/Zn, and the combined treatment with SFN/Zn was better than single treatments at ameliorating DCM. In addition, combined SFN and Zn treatment increased Nrf2 function and MT expression in the heart of OVE mice to a greater extent than SFN or Zn alone. This indicates that the dual activation of Nrf2 and MT by combined treatment with SFN and Zn may be more effective than monotherapy at preventing the development of DCM via complementary, additive mechanisms.

Both Peripheral Blood and Urinary miR-195-5p, miR-192-3p, miR-328-5p and Their Target Genes PPM1A, RAB1A and BRSK1 May Be Potential Biomarkers for Membranous Nephropathy.

BACKGROUND To identify noninvasive diagnostic biomarkers for membranous nephropathy (MN). MATERIAL AND METHODS The mRNA microarray datasets GSE73953 using peripheral blood mononuclear cells (PBMCs) of 8 membranous nephropathy patients and 2 control patients; and microRNAs (miRNA) microarray dataset GSE64306 using urine sediments of 4 membranous nephropathy patients and 6 control patients were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were respectively identified from PBMCs and urine sediments of membranous nephropathy patients, followed with functional enrichment analysis, protein-protein interaction (PPI) analysis, and miRNA-target gene analysis. Finally, the DEGs and the target genes of DEMs were overlapped to obtain crucial miRNA-mRNA interaction pairs for membranous nephropathy. RESULTS A total of 1246 DEGs were identified from PBMCs samples, among them upregulated CCL5 was found to be involved in the chemokine signaling pathway, and BAX was found to be apoptosis related; while downregulated PPM1A and CDK1 were associated with the MAPK signaling pathway and the p53 signaling pathway, respectively. The hub role of CDK1 (degree=18) and CCL5 (degree=12) were confirmed after protein-protein interaction network analysis in which CKD1 could interact with RAB1A. A total of 28 DEMs were identified in urine sediments. The 276 target genes of DEMs were involved in cell cycle arrest (PPM1A) and intracellular signal transduction (BRSK1). Thirteen genes were shared between the DEGs in PMBCs and the target genes of DEMs in urine sediments, but only hsa-miR-192-3p-RAB1A, hsa-miR-195-5p-PPM1A, and hsa-miR-328-5p-BRSK1 were negatively related in their expression level. CONCLUSIONS Both peripheral blood and urinary miR-195-5p, miR-192-3p, miR-328-5p, and their target genes PPM1A, RAB1A, and BRSK1 may be potential biomarkers for membranous nephropathy by participating in inflammation and apoptosis.

Effect of peritoneal dialysis versus hemodialysis on renal anemia in renal in end-stage disease patients: a meta-analysis.

The aim of this meta-analysis was to evaluate the effect of peritoneal dialysis (PD) and hemodialysis (HD) on renal anemia (RA) in renal disease patients by a meta-analysis. Relevant studies published before June 2015 were searched. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the effect of HD and PD on RA based on five indexes: hemoglobin, ferritin, transferrin saturation index, serum albumin, and parathyroid hormone. Sensitivity analysis and publication bias assessment were conducted to evaluate the stability and reliability of our results. A total of fourteen eligible studies with 1103 cases underwent HD and 625 cases underwent PD were used for this meta-analysis. There were no significant difference for levels of hemoglobin (SMD = -0.23, 95% CI: -0.74 to 0.28), ferritin (SMD = 0.01, 95% CI: -0.59 to 0.62), parathyroid hormone (SMD = 0.11, 95% CI: -1.53 to 1.75) and transferrin saturation index (SMD = -0.06, 95% CI: -0.67 to 0.56) between HD and PD group. However, the content of serum albumin in HD group was much more than that in PD group (SMD = 1.58, 95% CI: 0.35 to 2.81). Neither of the included studies could reverse the pooled side effect and Egger's test demonstrated no publication bias. Both of the two dialysis strategies have a similar effect on RA in renal disease patients.

Meta-analysis of the efficacy and safety of nucleotide/nucleoside analog monotherapy for hepatitis B virus-associated glomerulonephritis.

BACKGROUND/AIMS: Antiviral monotherapy is recommended for hepatitis B virus-associated glomerulonephritis (HBV-GN) treatment. Although considered superior to interferon-α in several respects, nucleotide/nucleoside analog (NA) monotherapy has not been studied. This metaanalysis evaluates the efficacy and safety of NA monotherapy for treating HBV-GN. METHODS: We searched for controlled clinical trials of NA monotherapy for HBVGN in the MEDLINE, Embase, Cochrane Library, Chinese BioMedical Literature on disc, Chinese National Knowledge Infrastructure, and Wanfang databases. Primary outcome measures were proteinuria remission, HBV-DNA negative conversion rate, and hepatitis B e-antigen (HBeAg) clearance. Secondary outcome measures were variations in proteinuria, serum albumin, alanine aminotransferase (ALT), and serum creatinine (Scr). RESULTS: Ten trials involving 325 patients were included: four randomized controlled trials, two cohort clinical trials, and four self-controlled studies. Based on the fixed-effects model, we found significant proteinuria remission rate improvement in the NA group (relative risk (RR): 3.60, 95% confidence interval (CI): 1.99 – 6.50), negative conversion rate of HBV-DNA (RR: 2.20, 95% CI: 1.55 – 3.13), and clearance of HBeAg (RR: 4.49, 95% CI: 1.29 – 15.67). Improvement in ALT (mean difference (MD): 56.60, 95% CI: 50.41 – 62.79) was found with the fixedeffects model, and a slight decrease in Scr (MD: 25.25, 95% CI: –17.11 – 67.61, p = 0.24) was shown. CONCLUSIONS: HBV-GN proteinuria remission with elevated serum albumin, decreased HBV replication, and improved HBeAg clearance could be achieved using NA monotherapy. Furthermore, NA monotherapy may protect renal function in HBV-GN patients by preventing Scr elevation.

12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance.

(1) BACKGROUND: 12-lipoxygenase (12-LO) is involved in the development of diabetic nephropathy (DN). In the present study, we investigated whether 12-LO inhibition may ameliorate type-2 DN (T2DN) by interfering with insulin resistance (IR); (2) METHODS: Rat glomerular mesangial cells, glomeruli and skeletal muscles were isolated and used in this study. Kidney histological changes were confirmed by periodic-acid Schiff staining; mRNA expression was detected by competitive reverse transcription polymerase chain reaction; and the protein level was determined by Western blot and the enzyme-linked immunosorbent assay, respectively; (3) RESULTS: The inhibition of 12-LO attenuated microalbuminuria (MAU) increases in type-2 diabetic rats, but not in type-1 diabetic rats. Infusion of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly increased the expression of angiotensin II (Ang II) and Ang II type 1 receptor (AT1R), but decreased the expression of AT1R-associated protein (ATRAP) in rat glomeruli, compared to the control. An in vitro study revealed that both 12(S)-HETE and insulin upregulated AT1R expression in rat mesangial cells. In the presence of p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190, the 12(S)-HETE-induced ATRAP reduction was significantly abolished. Interestingly, 12-LO inhibition did not influence AT1R expression in type-1 diabetic rats, but significantly abolished the increased AT1R and Ang II expression in glomeruli of type-2 diabetic rats. Furthermore, the inhibition of 12-LO significantly corrected impaired insulin sensitivity and fast serum insulin level, as well as the p-AMP-activated protein kinase (AMPK) reduction in skeletal muscle of type-2 diabetic rats; (4) CONCLUSION: The inhibition of 12-LO potentially ameliorated MAU by preventing IR through the downregulation of glomerular AT1R expression in T2DN.

A meta-analysis of liquid biopsy versus tumor histology for detecting EGFR mutations in non-small cell lung cancer.

OBJECTIVE: To assess the consistency of liquid biopsy and histologic analysis for detecting epidermal growth factor receptor (EGFR) gene mutations in patients with advanced non-small cell lung cancer (NSCLC). METHODS: The PubMed, Cochrane Library, and CNKI et al. databases were searched to collect studies comparing liquid biopsy and histopathologic specimens. The EGFR mutation status was extracted from the studies, and meta-analysis was carried out using Stata 12.0 software. RESULTS: We included 22 studies of 3359 NSCLC patients. In the meta-analysis, eight papers with a sample size of size <150 had an OR of 45, indicating that liquid biopsy had high sensitivity for detecting EGFR mutations. In addition, seven papers with a sample size ≥150, with an OR of 70, reported that liquid biopsy was highly susceptible to detecting EGFR mutations. The pooled diagnostic effect size of 6 for literature that included the T790M mutation was smaller than that of 69 for literature that did not include the T790M mutation, and I2 >50 %, showing that literature that did not include the T790M mutation was more heterogeneous. The combined diagnostic effect size of 34 in the exon 19 group was smaller than that in the group with no exon 19, with an I2>50 %. There was substantial heterogeneity in both the exon 19 group and the non-exon 19 group. The group with the L858R mutation had a greater diagnostic effect size of 28, lower I2, and less heterogeneity than the group without the L858R mutation. The exon 21 group had a larger pooled diagnostic effect size of 66, a smaller I2, and less heterogeneity than the group without exon 21. CONCLUSION: Liquid biopsy and histologic analysis have high concordance for detecting EGFR mutations in NSCLC. Liquid biopsy can provide an alternative technology for individualized treatment and monitoring of minimal residual disease (MRD) in advanced NSCLC patients with EGFR tyrosine kinase inhibitor-sensitive and drug resistance (T790M) mutations.

Developing a Modular Continuous Drug Product Manufacturing System with Real Time Quality Assurance for Producing Pharmaceutical Mini-Tablets.

The pharmaceutical industry has shown keen interest in developing small-scale modular manufacturing systems for producing medicinal products. These systems offer agile and flexible manufacturing, and are well-suited for use in situations requiring rapid production of drugs such as pandemics and humanitarian disasters. The creation of such systems requires the development of modular facilities for making solid oral drug products. In recent years, however, the development of such facilities has seen limited progress. This study presents a development of a prototype modular system that uses drop on demand (DoD) printing to produce personalized solid oral drug products. The system's operation is demonstrated for manufacturing mini-tablets, a category of pediatric drug products, in continuous and semi-batch modes. In this process, the DoD printer is used to generate molten formulation drops that are solidified into mini-tablets. These dosages are then extracted, washed and dried in a continuous filtration and drying unit which is integrated with the printer. Process monitoring tools are also incorporated in the system to track the critical quality attributes of the product and the critical process parameters of the manufacturing operation in real time. Future areas of innovation are also proposed to improve this prototype unit and to enable the development of advanced drug manufacturing systems based on this platform.

Ferroptosis and the bidirectional regulatory factor p53.

Ferroptosis is a type of regulated cell death characterized by iron-mediated lipid peroxidation, in contrast with apoptosis, autophagy, and necrosis. It can be triggered by many pathological processes, including cellular metabolism, tumors, neurodegenerative diseases, cardiovascular diseases, and ischemia-reperfusion injuries. In recent years, ferroptosis has been discovered to be associated with p53. P53 is a tumor suppressor protein with multiple and powerful functions in cell cycle arrest, senescence, cell death, repair of DNA damage, and mitophagy. Emerging evidence shows that ferroptosis plays a crucial role in tumor suppression by p53. P53 functions as a key bidirectional regulator of ferroptosis by adjusting metabolism of iron, lipids, glutathione peroxidase 4, reactive oxygen species, and amino acids via a canonical pathway. In addition, a noncanonical pathway of p53 that regulates ferroptosis has been discovered in recent years. The specific details require to be further clarified. These mechanisms provide new ideas for clinical applications, and translational studies of ferroptosis have been performed to treat various diseases.

Manufacturing pharmaceutical mini-tablets for pediatric patients using drop-on-demand printing.

The pharmaceutical industry has traditionally manufactured medicines in a limited range of dose strengths, with an emphasis on addressing the needs of the largest patient subgroups. This has disadvantaged smaller patient subsets, such as children, who often cannot find drug products in dosage levels suitable for their requirements. In recent years, development of pharmaceutical mini-tablets has emerged as an attractive solution to this problem. These are small-size dosages that offer attractive features such as flexible and personalized drug dosing, ease of swallowing, and tailored drug release, making them an excellent choice for administering medicines to children. This study presents a novel technique for manufacturing pharmaceutical mini-tablets, using a drop-on-demand (DoD) printing system. In this method, a DoD system is used to generate precise droplets of a melt-based formulation, which are then captured and solidified in an inert solvent bath to produce individual mini-tablets. The study also evaluates the performance of this technique for various formulations, and quantifies two critical quality attributes (CQAs) of the resulting mini-tablets: content uniformity and dissolution behavior. The findings demonstrate that the manufactured mini-tablets can meet regulatory specifications for both CQAs, and that their release profiles can be customized by modifying the excipients used. The study also discusses promising areas of application and limitations of this technique.

Metastatic germ cell tumor showing a durable response to the anti-PD-1 antibody toripalimab.

The outcome for patients with recurrent and metastatic germ cell tumors can be dismal, and novel salvage therapies are required for these patients. Here we describe a case of metastatic germ cell tumor in which 30% of cells were positive for PD-L1. This tumor achieved a durable response to toripalimab, a monoclonal anti-PD-1 antibody. Follow-up for 36 months post-treatment confirmed no disease progression. Continuous remission was maintained even when treatment was interrupted after 18 months because of an immune-related adverse event (allergic rhinitis). Thus, toripalimab may be an alternative choice for salvage therapy in patients with recurrent and metastatic germ cell tumors.

Rescue treatment for recurrent and metastatic germ cell tumors is limited. Immune checkpoint inhibitors have shown certain efficacy and safety in the treatment of a variety of tumors. Here we describe a case of metastatic germ cell tumor in which 30% of cells were positive for PD-L1. This tumor achieved a durable response to toripalimab, a monoclonal anti-PD-1 antibody. Follow-up for 36 months post-treatment confirmed no disease progression. We not only report the first use of toripalimab for the treatment of a metastatic germ cell tumor but also describe a patient with the longest sustained remission with an anti-PD-1 antibody to date.

AIDS with obesity, hypothyroidism and elevated serum creatinine: A case report.

Hypothyroidism is a prevalent endocrine illness with a variety of clinical symptoms, but among which elevated serum creatinine is uncommon. Hypothyroidism is also common in acquired immunodeficiency syndrome (AIDS) patients, especially those receiving highly active antiretroviral treatment (HAART). Here we present a case of a young AIDS patient with hypothyroidism, increased serum creatinine, and obesity. Despite the lack of a kidney biopsy, following levothyroxine (LT4) therapy, his serum creatinine recovered to normal levels, and weight loss, edema, weakness, rough skin and other clinical symptoms obtained notable improvement. This highlights the need of clinicians paying attention to whether thyroid function is aberrant in human immunodeficiency virus (HIV) patients with increased creatinine, edema and significant weight gain since prompt thyroid hormone therapy can restore the alterations in renal function and avoid invasive renal biopsy.

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefore, novel therapeutic methods, targets and biomarkers are urgently needed to meet clinical requirements. In recent years, increasing attention has been given to the role of epigenetic modification in the pathogenesis of DKD. Epigenetic variation mainly includes DNA methylation, histone modification and changes in the noncoding RNA expression profile, which are deeply involved in DKD-related inflammation, oxidative stress, hemodynamics, and the activation of abnormal signaling pathways. Since DKD is reversible at certain disease stages, it is valuable to identify abnormal epigenetic modifications as early diagnosis and treatment targets to prevent the progression of end-stage renal disease (ESRD). Because the current understanding of the epigenetic mechanism of DKD is not comprehensive, the purpose of this review is to summarize the role of epigenetic modification in the occurrence and development of DKD and evaluate the value of epigenetic therapies in DKD.

Organic solvent-free constructing of stable zeolitic imidazolate framework functional layer enhanced by halloysite nanotubes and polyvinyl alcohol on polyvinylidene fluoride hollow fiber membranes for treating dyeing wastewater.

In this study, zeolitic imidazolate framework (ZIF-8)/polyvinylidene fluoride (PVDF) loose nanofiltration (NF) hollow fiber membranes were fabricated by constructing ZIF-8 functional layer on the PVDF supporting membranes based on the vacuum-assisted assembly process. The ZIF-8 synthesis was completed in a water system, and the synthesized ZIF-8 suspension was directly added to polyvinyl alcohol (PVA) and halloysite nanotubes (HNTs) aqueous solution system without drying to prepare the casting solution, which could solve the agglomeration and poor dispersion problem of ZIF-8 particles. In addition, the embedded HNTs and the loaded PVA among the ZIF-8 layer could improve the bonding strength between the ZIF-8 layer and the supporting membranes. After constructing ZIF-8 functional layer, the pore size of supporting membranes decreased from more than 300 nm to several nanometers. Furthermore, the water contact angle reduced from 91.1° to 54.2°. Applied to treat dye wastewater, the prepared ZIF-8/PVDF membranes maintained high dye rejection (˃99.0 %) for Congo red (CR), but low salt rejection for NaCl (about 2 %). In addition, the flux could reach 21.6 L m-2h-1 after continuous filtration 360 min, exhibiting a potential for treating the dye/salt wastewater. In particular, there were no organic solvents used in the work, which provided a promising idea for solvent-free fabrication of loose NF membranes.

Role of sex hormones in diabetic nephropathy.

Diabetic nephropathy (DN) is the most common microvascular complication in diabetes and one of the leading causes of end-stage renal disease. The standard treatments for patients with classic DN focus on blood glucose and blood pressure control, but these treatments can only slow the progression of DN instead of stopping or reversing the disease. In recent years, new drugs targeting the pathological mechanisms of DN (e.g., blocking oxidative stress or inflammation) have emerged, and new therapeutic strategies targeting pathological mechanisms are gaining increasing attention. A growing number of epidemiological and clinical studies suggest that sex hormones play an important role in the onset and progression of DN. Testosterone is the main sex hormone in males and is thought to accelerate the occurrence and progression of DN. Estrogen is the main sex hormone in females and is thought to have renoprotective effects. However, the underlying molecular mechanism by which sex hormones regulate DN has not been fully elucidated and summarized. This review aims to summarize the correlation between sex hormones and DN and evaluate the value of hormonotherapy in DN.

As the SARS-CoV-2 virus evolves, should Omicron subvariant BA.2 be subjected to quarantine, or should we learn to live with it?

It has been nearly 35 months since the COVID-19 outbreak. The pathogen SARS-CoV-2 has evolved into several variants. Among them, Omicron is the fifth variant of concern which have rapidly spread globally during the past 8 months. Omicron variant shows different characteristics from previous variants, which is highly infectious, highly transmissible, minimally pathogenic, vaccine and antibody tolerant; however, it is less likely to cause severe illness, resulting in fewer deaths. Omicron has evolved into five main lineages, including BA.1, BA.2, BA.3, BA.4, and BA.5. Before BA.5, Omicron BA.2 sublineage was the dominant strain all over the world for several months. The experience of prevention and treatment against BA.2 is worth studying and learning for overcoming other Omicron subvariants. Although the Omicron subvariant BA.2 is significantly less severe than that caused by ancestral strains, it is still far more dangerous than influenza, and its long-term sequelae are unknown. Effective treatments are currently limited; therefore, effective defense may be the key to controlling the epidemic today, rather than just "living with" the virus.

Advances in the study of HLA class Ib in maternal-fetal immune tolerance.

The HLA class Ib molecule is an alloantigen that causes transplant rejection on behalf of individual human and plays an important role in maternal-fetal immune tolerance. Early studies on HLA class Ib focused on the mechanism of HLA-G-induced immune escape, but in recent years, studies on the mechanism of HLA-G have deepened and gradually explored the mechanism of HLA-E and HLA-F, which are also HLA class Ib molecules. In the maternal-fetal interface, trophoblast cells express HLA class Ib molecules to protect the fetus from maternal immune cells by binding to inhibitory receptors of decidual immune cells (DICs) and shifting Th1/Th2 balance toward Th2 bias. Further studies on the molecular mechanism of HLA class Ib molecules provide a reference for its application in the field of clinical assisted reproduction.

Relationships of the Trace Elements Zinc and Magnesium With Diabetic Nephropathy-Associated Renal Functional Damage in Patients With Type 2 Diabetes Mellitus.

Zinc (Zn) and magnesium (Mg) are essential trace elements in humans. Their deficiency may be associated with inflammation and oxidative stress (OS) in patients with diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. We aimed to investigate the relationships between circulating concentrations of Zn and Mg and pro-inflammatory factors with DN-associated renal functional damage in patients with type 2 diabetes mellitus (T2DM). To this end, we studied 20 healthy people, 24 patients with T2DM, and 59 patients with T2DM and T2DN. Serum and urine Zn and Mg concentrations were measured using the 2-(5-nitro-2-pyridylazo)-5-(N-propyl-N-sulfopropylamine) phenol (nitro-PAPS) chromogenic method and the xylidyl blue method, respectively, and the circulating concentrations of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α)] were measured using flow cytometry. The serum concentrations of Zn and Mg were significantly lower in patients with T2DM and DN than in healthy controls. Serum Zn, urine Zn, and urine Mg concentrations decreased, while those of IL-6 and IL-8 increased with the progression of DN-associated renal functional damage. Furthermore, the serum and urine Zn concentrations negatively correlated with the serum IL-6 and IL-8 concentrations. Notably, the serum Zn concentration was found to independently protect against DN in patients with T2DM. Hypozincemia may be associated with the T2DN-associated renal functional damage because it exacerbates inflammation.