Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer.

Despite the continuous developments and advancements in the treatment of gastric cancer (GC), which is one of the most prevalent types of cancer in China, the overall survival is still poor for most patients with advanced GC. In recent years, with the progress in tumor immunology research, attention has shifted toward immunotherapy as a therapeutic approach for GC. Programmed cell death protein 1 (PD-1) inhibitors, as novel immunosuppressive medications, have been widely utilized in the treatment of GC. However, many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy. To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy, to maximize the clinical activity of immunosuppressive drugs, and to elicit a lasting immune response, it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients. This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment, aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Janus Structure Construction of Polyester-Cotton Fabrics for Achieving Excellent Moisture, Moisture-Permeability, and Antibacterial Capability.

Integration of hydrophobic and antibacterial functionalities into polyester-cotton blended (PTCO) textiles has attracted more attention but remains a challenge. Here, a Janus fabric with antibacterial effect, hydrophobicity, and enhanced moisture-permeability is fabricated using a "mist polymerization" approach. The PET fibers in the PTCO fabric are amino-functionalized through ammonolysis reactions of PET molecules with HDA, and mist treatments of poly lauryl methacrylate (PLMA) and poly(DMC-co-MA) (PDM) are applied on the two side surfaces of the PTCO-HDA fabric, respectively. The resulting Janus fabric exhibits an antibacterial rate of 99.9% against both E. coli and S. aureus, along with a hydrophobic property on its single side (PTCO-HDA@PLMA). Additionally, the establishment of a surface-free energy gradient across the fabric confers superior moisture-permeability to the Janus fabric, offering advantages in preserving textile comfort. Moreover, this approach does not significantly compromise the original fabric properties, such as mechanical strength, moisture permeability, and fabric softness. The proposed method offers a straightforward and scalable strategy for textile finishing, demonstrating great potential in expanding the application scope of PTCO fabrics, and it may hold a pivotal role in diverse applications, notably encompassing home textiles, wound dressings, and high-performance sportswear.

Lewis base promoted [4 + 2] annulation of o-acylamino-aryl MBH carbonates with isatin.

The first example of Lewis base promoted [4 + 2] annulation between o-acylamino-aryl MBH carbonates and isatin has been developed. This methodology exhibits excellent substrate applicability and has synthesized 1,4-dihydrospiro benzo[d][1,3]oxazine-oxindoles with yields up to 98%. The practical value of this method is underscored by its successful application in a 50-fold scale-up.

Comparison of early and fully expanded blastocysts on pregnancy and birth outcomes in patients with fresh IVF/ICSI cycles: A retrospective cohort study.

OBJECTIVE: To investigate the effect of the early blastocyst on pregnancy and birth outcomes in patients in vitro fertilization/(early rescue) intracytoplasmic sperm injection-embryo transfer [IVF/(early rescue)ICSI-ET] cycles. METHODS: In this retrospective cohort study, 289 patients with single-blastocyst transfer within IVF/(early rescue)ICSI-ET treatment cycle were included and divided into the early (n = 48, Gardner stage = 1 or 2) and the fully expanded blastocyst (n = 241, Gardner stage ≥ 3) groups. The differences in pregnancy and birth outcomes between the two groups were compared. RESULTS: There was no significant differences between the two groups in baseline indicators, including demographic characteristics and clinical treatment (P> 0.05).The clinical outcomes indicators in the early and the fully expanded blastocyst groups were compared, including the number of transferable embryos on the third day (D3)5.0 (4.0, 6.8) vs. 6.0 (5.0, 8.0) (P = 0.001), the number of remaining embryos frozen per cycle 1.0 (0.3, 2.0) vs. 3.0 (2.0, 5.0) (P<0.001); the number of cycles of unfrozen embryos 13/48 (27.1%) vs. 12/241 (5.0%) (P<0.001); the pregnancy outcome including the clinical pregnancy rate (CPR) 20/48 (41.7%) vs. 129/241 (53.5%) (P>0.05); the live birth rate (LBR)15/48 (31.3%) vs.106/241 (44.0%) (P>0.05). There were no significant differences in birth outcomes, such as gestational week of labor, mode of delivery, neonatal birth weight, height, Apgar score, sex ratio, and birth defects between the two groups (P>0.05).Multivariate binary logistic regression showed the same result, i.e., early blastocyst transfer in fresh cycle was not a risk factor for clinical pregnancy (OR = 0.516, 95% CI = 0.260-1.022) and live birth (OR = 0.521, 95% CI = 0.252-1.079). CONCLUSION: Compared with the fully expanded blastocyst group, the CPR and LBR in the early blastocyst group of the fresh transfer cycles were relatively ideal, and there were no significant differences in birth outcomes and neonatal status between the two groups.

Causal relationships between gut microbiota, gut metabolites, and diabetic neuropathy: A mendelian randomization study.

BACKGROUND: Previous studies have shown a strong correlation between gut microbiota and diabetes and its associated complications. We aimed to evaluate the causal relationships between the gut microbiota, gut metabolites, and diabetic neuropathy. METHODS: Summary statistics of 211 gut microbiota and 12 gut-related metabolites (ß-hydroxybutyric acid, betaine, trimethylamine-N-oxide, carnitine, choline, glutamate, kynurenine, phenylalanine, propionic acid, serotonin, tryptophan, and tyrosine) were obtained from previous genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) design was used to estimate the effects of gut microbiota and gut metabolites on the risk of diabetic neuropathy based on FinnGen GWAS. RESULTS: Higher levels of Acidaminococcaceae (OR = 0.62; 95%CI = 0.46 to 0.84; P = 0.002), Peptococcaceae (OR = 0.70; 95%CI = 0.54 to 0.90; P = 0.006), and Eubacterium coprostanoligenes group (OR = 0.68; 95%CI = 0.50 to 0.93; P = 0.016) are genetically determined to provide protection against diabetic neuropathy. Conversely, the presence of Alistipes (OR = 1.65; 95%CI = 1.18 to 2.31; P = 0.003), ChristensenellaceaeR7 group (OR = 1.52; 95%CI = 1.03 to 2.23; P = 0.033), Eggerthella (OR = 1.28; 95%CI = 1.05 to 1.55; P = 0.014), RuminococcaceaeUCG013 (OR = 1.35; 95%CI = 1.01 to 1.82; P = 0.046), and Firmicutes (OR = 1.42; 95%CI = 1.05 to 1.93; P = 0.023) increases the risk of diabetic neuropathy. Moreover, a correlation has been identified between diabetic neuropathy and two gut metabolites: betaine (OR = 0.95; 95%CI = 0.90 to 1.00; P = 0.033) and tyrosine (OR = 1.03; 95%CI = 1.01 to 1.06; P = 0.019). Sensitivity analysis indicated robust results with no sign of heterogeneity or pleiotropy. CONCLUSION: The present study elucidated the impact of specific gut microbiota and gut metabolites on the susceptibility to diabetic neuropathy. Interventions targeting the improvement of the gut microbiota diversity and composition hold considerable promise as a potential strategy.

Primary Robotic Versus Conventional Laparoscopic Roux-en-Y Gastric Bypass in Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Robotic Roux-en-Y gastric bypass (RRYGB) and conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) are commonly performed as primary bariatric procedures. The aim of this article was to assess the role of RRYGB in patients undergoing primary bariatric procedures. METHODS: All of the qualified studies were selected from the PubMed, Embase, and Web of Science databases, etc. We mainly compared the outcomes and safety between RRYGB and LRYGB. The outcomes evaluation included surgical effect and surgical safety. RESULT: In total, 35 studies containing 426,463 patients were selected. The mortalities of patients adopting these 2 bariatric procedures were similar (RRYGB: 59/28,023, 0.21%; LRYGB: 612/397,945, 0.15%). We found no significant difference between RRYGB and LRYGB in the incidence of postoperative complications (30-day: OR=1.06, P =0.18; 1-y: OR=1.06, P =0.92). The incidence of 30-day readmission after the operation was higher in RRYGB patients (OR=1.24, P =0.003). However, we found that the RRYGB group had a lower incidence of anastomotic stricture 1 year after the operation when compared with LRYGB (OR=0.35, P =0.0004). The 1-year %EBMIL of these 2 groups was similar (78.53% vs. 76.02%). There was no significant difference in length of hospital stay (LOS) (WMD=-0.03d, P =0.59), conversion rate (OR=0.84, P =0.75), or anastomotic leak (OR=1.00, P =0.99) between these 2 groups. The mean hospital charges were higher in the RRYGB group ($11234.75 vs. $9468.58). CONCLUSION: This systematic review and meta-analysis showed no significant advantage of RRYGB in surgical effect or reduction of intraoperative complications. RRYGB may reduce the incidence of some postoperative long-term complications. The mean hospital charges of RRYGB were higher.

Assessment of Transplant Renal Artery Stenosis with Non-contrast-Enhanced Magnetic Resonance Angiography: Comparison with Digital Subtraction Angiography.

RATIONALE AND OBJECTIVES: Early diagnosis of transplant renal artery stenosis (TRAS) is crucial for salvaging kidney function and improving patient prognosis. The purpose of this study was to evaluate image quality of non-contrast-enhanced MR angiography (NCE-MRA) and the value of NCE-MRA in evaluating TRAS compared to DSA. MATERIALS AND METHODS: In 60 patients with TRAS confirmed by DSA, the degree of TRAS was assessed using balanced triggered angiography non-contrast-enhanced (B-TRANCE) MR angiography and was compared to that of DSA. Image quality for NCE-MRA was assessed independently by two radiologists. The Wilcoxon signed-rank test was used to compare NCE-MRA with DSA in assessing TRAS degree. Specificity, sensitivity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of NCE-MRA for the detection of marked (≥50%) TRAS were calculated. RESULTS: The image quality of NCE-MRA based on the B-TRANCE technology of transplanted renal arteries was sufficient (excellent in 81.67%, good in 8.33%, moderate in 6.67%, and non-diagnostic in 3.33%) and had a high inter-observer reproducibility (Kappa=0.836). DSA helped identify severe, moderate, and mild stenosis in 6, 32, and 22 arteries, respectively. No significant difference in the extent of TRAS between NCE-MRA and DSA were observed (P = 0.317). The specificity, sensitivity, accuracy, PPV, and NPV of NCE-MRA in detecting marked (≥50%) TRAS were 90.91%, 100%, 96.55%, 94.74%, and 100%, respectively. CONCLUSION: NCE-MRA based on B-TRANCE technology has shown promising consistency with DSA in evaluating TRAS and yielding high sensitivity, specificity, and accuracy in assessing the severity of TRAS.

Diverse Synthesis of Fused Polyheterocyclic Compounds via [3 + 2] Cycloaddition of In Situ-Generated Heteroaromatic N-Ylides and Electron-Deficient Olefins.

[3 + 2] Cycloaddition reactions of heteroaromatic N-ylides with electron-deficient olefins have been developed. The heteroaromatic N-ylides, in situ generated from N-phenacylbenzothiazolium bromides, can smoothly react with maleimides under very mild conditions, affording fused polycyclic octahydropyrrolo[3,4-c]pyrroles in good-to-excellent isolated yields. This reaction concept could also be extended to 3-trifluoroethylidene oxindoles and benzylidenemalononitriles as electron-deficient olefins for accessing highly functionalized polyheterocyclic compounds. A gram-scale experiment was also carried out to verify the practicability of the methodology.

Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms.

OBJECTIVE: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. METHODS: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. RESULTS: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin-angiotensin-aldosterone system, and promotion of ß-cell sensitivity to insulin. CONCLUSION: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Evaluating renal iron overload in diabetes mellitus by blood oxygen level-dependent magnetic resonance imaging: a longitudinal experimental study.

BACKGROUND: Iron overload plays a critical role in the pathogenesis of diabetic nephropathy. Non-invasive evaluation of renal iron overload in diabetes in the management and intervention of diabetic nephropathy is of great significance. This study aimed to explore the feasibility of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in evaluating renal iron overload in diabetes using a rabbit model. METHODS: The rabbits were randomly divided into control, iron-overload (I), diabetes (D), and diabetes with iron-overload (DI) groups (each n = 19). The diabetes models were generated by injecting intravenous alloxan solution, and the iron-overload models were generated by injecting intramuscular iron-dextran. BOLD MRI was performed immediately (week 0) and at week 4, 8, and 12 following modeling. The differences in renal cortex (CR2*) and outer medulla R2* (MR2*) and the ratio of MR2*-CR2* (MCR) across the different time points were compared. RESULTS: Iron was first deposited in glomeruli in the I group and in proximal tubular cells in renal cortex in the D group. In the DI group, there was iron deposition in both glomeruli and proximal tubular cells at week 4, and the accumulation increased subsequently. The degree of kidney injury and iron overload was more severe in the DI group than those in the I and D groups at week 12. At week 8 and 12, the CR2* and MR2* in the DI group were higher than those in the I and D groups (all P < 0.05). The MCR in the I, D, and DI groups decreased from week 0 to 4 (all P < 0.001), and that in the I group increased from week 8 to 12 (P = 0.034). CR2* and MR2* values displayed different trends from week 0-12. Dynamic MCR curves in the D and DI groups were different from that in the I group. CONCLUSION: It presents interactions between diabetes and iron overload in kidney injury, and BOLD MRI can be used to evaluate renal iron overload in diabetes.

Association between thyroid hormones and skeletal muscle and bone in euthyroid type 2 diabetes patients.

Background: The impact of thyroid hormones within their normal ranges on skeletal muscle and bone in patients with type 2 diabetes mellitus (T2DM) remains unknown. The purpose of this study was to investigate the relationships of thyroid hormones with muscle and bone in euthyroid patients with T2DM. Methods: This cross-sectional study included 344 euthyroid T2DM patients. Muscle mass and bone mineral density were measured by dual-energy X-ray absorptiometry. The levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxin (FT4) were measured by electrochemiluminescence immunoassay. Results: The results revealed that FT3 was positively correlated with body mass index (BMI) in male patients after age correction. In men, FT4 was negatively correlated with body weight, BMI, total muscle mass, appendicular skeletal muscle mass (ASM), and ASM index (ASMI), while FT3/FT4 was positively correlated with body weight, BMI, total muscle mass, ASM, and ASMI after age correction. In women, FT4 was negatively correlated with ASM and ASMI, while FT3/FT4 was positively correlated with ASM and ASMI after age correction. FT3/FT4 was significantly lower in men with low muscle mass than in those with normal muscle mass. The age-adjusted odds for incident low muscle mass comparing the lowest and highest FT3/FT4 increased in men. Conclusions: FT3/FT4 was positively correlated with ASM and ASMI in both men and women. Therefore, FT3/FT4 may be a parameter indicative of low muscle mass in euthyroid men with T2DM.

Access to 4-Trifluoromethyl Quinolines via Cu-Catalyzed Annulation Reaction of Ketone Oxime Acetates with ortho-Trifluoroacetyl Anilines under Redox-Neutral Conditions.

An efficient Cu-catalyzed annulation reaction of ketone oxime acetates with ortho-trifluoroacetyl anilines has been disclosed. With the developed protocol, a series of 4-trifluoromethyl quinolines were obtained in good to excellent yields (58-99%) under redox-neutral conditions. The protocol also could be extended to ferrocene-based ketone oxime acetates for the construction of ferrocene-substituted fluorine-containing quinolines.

Inverse Electron-Demand Aza-Diels-Alder Reaction of α,ß-Unsaturated Thioesters with In Situ-Generated 1,2-Diaza-1,3-dienes for the Synthesis of 1,3,4-Thiadiazines.

A highly regioselective inverse electron-demand aza-Diels-Alder reaction of α,ß-unsaturated thioesters with 1,2-diaza-1,3-dienes generated in situ from α-halogeno hydrazones was developed. With α,ß-unsaturated thioesters as C═S dienophiles, the developed protocol enables the formation of diverse 3,6-dihydro-2H-1,3,4-thiadiazine derivatives in excellent yields. In the presence of lithium aluminum hydride, 3,6-dihydro-2H-1,3,4-thiadiazine derivatives could be further transformed into 5,6-dihydro-4H-1,3,4-thiadiazines in good yields.

α-Nitrosostyrenes as Three-Atom Units for the (3+1) Cyclization Reaction: Facile Access to 2,3-Dihydrodiazete N-Oxides and Their Diversified Synthetic Conversions.

An unprecedented (3+1) cyclization of α-nitrosostyrenes, generated in situ from α-bromooximes, and N-tosyloxycarbamates was developed, which enables the synthesis of a range of structurally unique and hitherto unexplored 2,3-dihydrodiazete N-oxides in moderate to high yields. The products possess a highly strained four-membered ring structure containing two nitrogen atoms. The synthetic applicability of the products was also demonstrated by many important conversions to diverse nitrogen-containing compounds.

Cepharanthine sensitizes human triple negative breast cancer cells to chemotherapeutic agent epirubicin via inducing cofilin oxidation-mediated mitochondrial fission and apoptosis.

Inhibition of autophagy has been accepted as a promising therapeutic strategy in cancer, but its clinical application is hindered by lack of effective and specific autophagy inhibitors. We previously identified cepharanthine (CEP) as a novel autophagy inhibitor, which inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. In this study we investigated whether and how inhibition of autophagy/mitophagy by cepharanthine affected the efficacy of chemotherapeutic agent epirubicin in triple negative breast cancer (TNBC) cells in vitro and in vivo. In human breast cancer MDA-MB-231 and BT549 cells, application of CEP (2 µM) greatly enhanced cepharanthine-induced inhibition on cell viability and colony formation. CEP interacted with epirubicin synergistically to induce apoptosis in TNBC cells via the mitochondrial pathway. We demonstrated that co-administration of CEP and epirubicin induced mitochondrial fission in MDA-MB-231 cells, and the production of mitochondrial superoxide was correlated with mitochondrial fission and apoptosis induced by the combination. Moreover, we revealed that co-administration of CEP and epirubicin markedly increased the generation of mitochondrial superoxide, resulting in oxidation of the actin-remodeling protein cofilin, which promoted formation of an intramolecular disulfide bridge between Cys39 and Cys80 as well as Ser3 dephosphorylation, leading to mitochondria translocation of cofilin, thus causing mitochondrial fission and apoptosis. Finally, in mice bearing MDA-MB-231 cell xenografts, co-administration of CEP (12 mg/kg, ip, once every other day for 36 days) greatly enhanced the therapeutic efficacy of epirubicin (2 mg/kg) as compared with administration of either drug alone. Taken together, our results implicate that a combination of cepharanthine with chemotherapeutic agents could represent a novel therapeutic strategy for the treatment of breast cancer.

The mediating role of psychological capital between Dayadi stress and job burnout in female nurses with two children.

BACKGROUND: This study aims to understand the job burnout status of female nurses with two children and explore the mediating role of psychological capital between dyadic stress and job burnout. METHODS: We used a random sampling method to select 386 female nurses with two children from four tertiary level hospitals between July and October 2020. A general data questionnaire, dyadic stress scale, psychological capital scale, and job burnout scale were used for the investigation and analysis. RESULTS: The psychological capital score of nurses with two children was 84.87±15.45, the dyadic stress was 34.48±6.18, and the job burnout score was 68.28±14.28. Factors affecting the binary stress score, psychological capital score, and job burnout score of nurses with two children included age, professional title, length of service, monthly income, age of the first child, the type of childcare arrangements, and hospital department. The psychological capital score was negatively correlated with the job burnout score (r=-0.617, P<0.01). There was a positive correlation between the dyadic stress score and the job burnout score (r=0.539, P<0.01), and a negative correlation between the psychological capital score and the binary stress score (r=-0.528, P<0.01). The mediating effect of psychological capital was 0.199, accounting for 36.71% of the total effect. CONCLUSIONS: The results showed that dyadic stress and job burnout in nurses with two children were at a high level and that psychological capital played a partial mediating role between binary stress and job burnout.

Inverse Electron-Demand Aza-Diels-Alder Reaction of Cyclic Enamides with 1,2-Diaza-1,3-dienes in Situ Generated from α-Halogeno Hydrazones: Access to Fused Polycyclic Tetrahydropyridazine Derivatives.

An efficient inverse electron-demand aza-Diels-Alder reaction of cyclic enamides and 1,2-diaza-1,3-dienes, which could be readily formed in situ from α-halogeno hydrazones and a base, has been successfully developed. With the developed approach, a wide range of fused polycyclic tetrahydropyridazines were smoothly obtained in up to 99% yield under benign reaction conditions. This reaction concept was also extended to acyclic enamide substrates for accessing 1,4,5,6-tetrahydropyridazines. A gram-scale experiment and further derivatizations of the polycyclic tetrahydropyridazine products were also conducted to verify the practicability of the methodology.

A cross-sectional study: an assessment of low muscle mass and osteoporosis in type 2 diabetes mellitus patients with a high glycated hemoglobin level.

BACKGROUND: Low muscle mass and osteoporosis are commonly observed in individuals with type 2 diabetes mellitus (T2DM). We investigated the prevalence of low muscle mass and osteoporosis in patients with T2DM who had high glycated hemoglobin (HbA1c) levels. METHODS: We included 187 Chinese patients with T2DM who were aged ⩾50 years and evaluated their body composition using dual-energy X-ray absorptiometry. We measured levels of fasting blood glucose, HbA1c, B collagen-specific sequences (B-CTX), osteocalcin (OC), propeptide of type 1 procollagen (P1NP), and 25-hydroxy vitamin D. RESULTS: Of the total patients, 82 were men and 105 were women. The prevalence rates of low muscle mass, osteopenia, and osteoporosis were 35.8%, 38.0%, and 31.0%, respectively. The prevalence rate of low muscle mass was significantly higher in women with HbA1c levels >9.0% than in those with HbA1c levels <9.0%. The prevalence rates of osteopenia and osteoporosis in men with HbA1c levels >9.0% differed significantly from those with HbA1c levels <9.0%. The appendicular skeletal muscle mass index (ASMI), trunk muscle mass, lumbar spinal bone mineral content (BMC), lumbar spine BMD, femoral BMC, and femoral BMD were significantly decreased, and the serum levels of B-CTX, OC, and P1NP were significantly increased in patients with T2DM who had osteoporosis. The ASMI was associated with osteopenia/osteoporosis in men and women with T2DM. CONCLUSIONS: In patients with T2DM, high HbA1c levels were associated with higher prevalence rates of low muscle mass in women and osteoporosis in men, and ASMI was a risk factor of osteoporosis.

Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease.

Angiopoietin-like protein 2 (ANGPTL2) stimulates inflammation and is important in the pathogenesis of diabetic kidney disease (DKD). Irbesartan is helpful in reducing diabetes-induced renal damage. In this study, the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined. Wistar rats were divided into normal, DKD, and DKD + irbesartan groups. The DKD + irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage. The 24-h urinary albumin was determined each week, renal pathological changes were observed, and expression of ANGPTL2 and nuclear factor-kappa B (NF-κB) in rat renal tissue was assessed by immunohistochemistry. Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations (0, 25, 50, and 75 ºg/mL). Expression of ANGPTL2 and phosphorylated IκB-α was assessed by Western blotting. The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1 (MCP-1) were assessed by real-time polymerase chain reaction. The DKD rats displayed proteinuria, podocyte injury, and increased ANGPTL2 and NF-κB expression. All were relieved by irbesartan treatment. In podocytes cultured in elevated glucose, ANGPTL2 and phosphorylated IκB-α were overexpressed at the protein level, and ANGPTL2 and MCP-1 were highly expressed at the mRNA level. Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level. The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.