IgG4-Related Disease in a 90-Year-Old Man with an 18-Year Disease Course: A Case Report.

IgG4-related disease (IgG4-RD) is a multi-organ inflammatory immune-mediated illness caused by IgG4-secreting plasma cells infiltrating the tissue. This condition usually affects elderly men. A 90-year-old Chinese male was diagnosed with IgG4-RD based on the new 2019 ACR/EULAR classification criteria, as he had multiple organ involvement. After receiving treatment with glucocorticoids, leflunomide, and gamma-globulin, the patient's clinical symptoms significantly improved, confirming the accuracy of the diagnosis. The patient had an 18-year medical history during which the disease progressively worsened due to delayed diagnosis and treatment. Although the relevant symptoms were alleviated with appropriate medication, the overall treatment process encountered challenges. Due to the patient's relative lack of adrenocortical function, he experienced symptoms such as nausea, exhaustion, and loss of appetite during the hormone reduction process. Therefore, timely intervention is especially crucial to address the side effects of hormone therapy.

Factors associated with concomitant prostate cancer in benign prostatic hyperplasia patients aged 60 years and above.

OBJECTIVE: Prostate hyperplasia and cancer are more prevalent in middle-aged and elderly men. Previous studies have linked both disorders to androgen receptors. Herein, efforts were made to identify factors associated with prostate cancer in patients ≥60 years, aiming to enhance their health management. METHODS: An analytical framework was established utilizing the "Prostate Cancer Early Warning Dataset" from the National Clinical Medical Science Data Center. Variables selection was conducted through LASSO regression, followed by multifactorial logistic stepwise regression to construct a predictive model. RESULTS: A total of 1,502 patients with BPH and 294 with combined PCa were hereby included. Multivariate regression delineated several independent predictors of PCa coexistence, including age (OR [95% CI]: 1.06 [1.04-1.09], p < 0.001), fPSA/tPSA ratio (OR [95% CI]: 0.01 [0.002-0.05], p < 0.001), serum inorganic phosphorus (OR [95% CI]: 5.85 [2.61-13.15], p < 0.001), globulin levels (OR [95% CI]: 1.06 [1.02-1.11], p = 0.005), serum potassium (OR [95% CI]: 0.58 [0.40-0.86], p = 0.006), low-density lipoprotein (LDL) cholesterol (OR [95% CI]: 1.28 [1.06-1.54], p = 0.009), among others. CONCLUSION: The analysis revealed connections between PCa occurrence in men aged over 60 and BPH, along with specific serum biomarkers such as inorganic phosphorus, globulin, LDL cholesterol, lower fPSA/tPSA ratios and serum potassium.

Effects of different sodium-glucose cotransporter 2 inhibitors in heart failure with reduced or preserved ejection fraction: a network meta-analysis.

Background: This systematic review and meta-analysis aimed to explore the effects of different sodium-glucose cotransporter-2 inhibitors (SGLT2i) on prognosis and cardiac structural remodeling in patients with heart failure (HF). Methods: Relevant studies published up to 20 March 2024 were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library CNKI, China Biomedical Literature Service, VIP, and WanFang databases. We included randomized controlled trials of different SGLT2i and pooled the prognosis data of patients with HF. We compared the efficacy of different SGLT2i in patients with HF and conducted a sub-analysis based on left ventricular ejection fraction (LVEF). Results: We identified 77 randomized controlled trials involving 43,561 patients. The results showed that SGLT2i significantly enhanced outcomes in HF, including a composite of hospitalizations for HF and cardiovascular death, individual hospitalizations for HF, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, left atrial volume index (LAVi), and LVEF among all HF patients (P < 0.05) compared to a placebo. Sotagliflozin was superior to empagliflozin [RR = 0.88, CI (0.79-0.97)] and dapagliflozin [RR = 0.86, CI (0.77-0.96)] in reducing hospitalizations for HF and CV death. Dapagliflozin significantly reduced hospitalizations [RR = 0.51, CI (0.33-0.80)], CV death [RR = 0.73, CI (0.54-0.97)], and all-cause mortality [RR = 0.69, CI (0.48-0.99)] in patients with HF with reduced ejection fraction (HFrEF). SGLT2i also plays a significant role in improving cardiac remodeling and quality of life (LVMi, LVEDV, KCQQ) (P < 0.05). Among patients with HF with preserved ejection fraction (HFpEF), SGLT2i significantly improved cardiac function in HFpEF patients (P < 0.05). In addition, canagliflozin [RR = 0.09, CI (0.01-0.86)] demonstrated greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF patients. Conclusion: Our systematic review showed that SGLT2i generally enhances the prognosis of patients with HF. Sotagliflozin demonstrated superiority over empagliflozin and dapagliflozin in a composite of hospitalization for HF and CV death in the overall HF patients. Canagliflozin exhibited greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF. Overall, the efficacy of SGLT2i was greater in HFrEF patients than in HFpEF patients.

Regional intra-arterial vs. systemic chemotherapy for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis.

Introduction: Pancreatic cancer is a highly aggressive malignancy with limited response to chemotherapy. This research aims to compare the effectiveness and safety of regional intra-arterial chemotherapy (RIAC) with conventional systemic chemotherapy in treating advanced stages of pancreatic cancer. Methods: A comprehensive literature review was conducted using databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Studies assessing the comparative outcomes of RIAC and systemic chemotherapy were included. Data extraction and quality evaluation were performed independently by two researchers. Statistical analysis was conducted using STATA16 software, calculating odds ratios (OR), risk differences (RD), and 95% confidence intervals (CI). Results: Eleven studies, comprising a total of 627 patients, were included in the meta-analysis. The findings showed that patients undergoing RIAC had significantly higher rates of partial remission (PR) compared to those receiving systemic chemotherapy (OR = 2.23, 95% CI: 1.57, 3.15, I2= 0%). Additionally, the rate of complications was lower in the RIAC group (OR = 0.45, 95% CI: 0.33, 0.63, I2= 0%). Moreover, patients treated with RIAC had notably longer median survival times. Discussion: The results of this research indicate that RIAC is associated with a higher rate of partial remission, improved clinical benefits, and fewer complications compared to systemic chemotherapy in the management of advanced pancreatic cancer. These findings suggest that RIAC may be a more effective and safer treatment option for patients with advanced stages of pancreatic cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023404637.

Linezolid induced hypoglycemia and anemia: A case report.

Key Clinical Message: Linezolid (LZD) is an efficient addition antibiotic against multidrug-resistant strains. However, clinicians should pay attention to the adverse reactions such as hypoglycemia and anemia in using LZD, especially in elderly patients and patients with abnormal liver and kidney function who need to use LZD for a long time. Abstract: Severe hypoglycemia and anemia caused by linezolid (LZD) are rare, with potentially serious adverse effects. The report of LZD-induced hypoglycemia and anemia is extremely rare. Thus far, this is the first report. We presented LZD-induced recurrent hypoglycemia and anemia in a 93-year-old patient who has been prescribed LZD 600 mg once daily for 42 days for treatment of tuberculosis (TB) pleurisy and pneumonia. The patient began to experience recurrent hypoglycemic episodes and anemia 5 days and 2 weeks after LZD medication, respectively. Using Naranjo's Adverse Drug Reaction Assessment Scale, the patient scored 8 points with the category of "probable". His hypoglycemia and anemia gradually improved 1 month after LZD withdrawal. Clinicians should pay attention to the adverse reactions such as hypoglycemia and anemia in using LZD, especially in elderly patients and patients with abnormal liver and kidney function who need to use LZD for a long time. Patients should regularly monitor blood routine, blood glucose, and liver and kidney functions during LZD exposure, which may avoid adverse reactions and improve their prognosis.

Palliative care and Chinese medicine in a centenarian with primary hepatocellular carcinoma and 27-month follow-up: A case report.

The number of centenarians with cancer is increasing as the global population ages. The diagnosis and treatment for centenarians with tumor sometimes are specific, and there are currently less appropriate guidelines as references. We report a 104-year-old man with asymptomatic primary liver cancer (PLC) whose family decided to receive conservative and palliative care. The patient has been followed up for 27 months. He has been mainly received Chinese herbal medicine (CHM), nutritional support and thymalfasin injection intermittently, etc. During the 27-month follow-up, the patient has showed good compliance and tolerance without any complications of the tumor. Conclusion: Individualized palliative care and complementary medicine, based on multidisciplinary evaluation, traditional Chinese medicine, consultation with patients and their families about treatment options, etc., may help improve the life quality of centenarians with end-stage tumors.

High G Tolerance and Cardiopulmonary Reserve Function in Healthy Air Force Aviators.

INTRODUCTION: There is no consensus on whether cardiopulmonary reserve affects the risk of gravity-induced loss of consciousness (G-LOC) or almost loss of consciousness (A-LOC). Few previous studies have used cardiopulmonary exercise testing (CPET) to assess cardiopulmonary reserve function (CPRF) of fighter aviators. We compared CPET-related parameters in G-LOC/A-LOC and non-G-LOC/A-LOC fighter aviators to explore the effect of cardiopulmonary reserve function on G tolerance.METHODS: A total of 264 male fighter aviators with more than 500 h of flight experience participated in the study, all of whom underwent CPET and human centrifuge testing. We divided the aviators into two groups based on whether they experienced G-LOC/A-LOC during the human centrifuge test and compared the CPET parameters between the two groups.RESULTS: A total of 37 aviators (14%) experienced G-LOC/A-LOC. There were no significant differences in age (26.65 ± 4.30 vs. 26.01 ± 4.95), height (173.68 ± 4.21 vs. 173.55 ± 3.37), weight (69.51 ± 6.22 vs. 69.63 ± 6.01), or body mass index (23.06 ± 2.11 vs. 23.11 ± 1.82) between the two groups. Forced vital capacity (FVC) (4.95 ± 0.87 vs. 4.65 ± 0.79) and forced expiratory volume in 1 s (FEV1) divided by FVC (FEV1/FVC) (79.88 ± 7.24 vs. 83.72 ± 9.24) of pulmonary function of the G-LOC/A-LOC group was significantly lower than that of the non-G-LOC/A-LOC group. There was no significant difference in CPET-related parameters between the two groups.DISCUSSION: In conclusion, FEV1/FVC may be a factor affecting aviators' G-LOC/A-LOC, meaning aviators with slightly lower ventilation are more likely to experience G-LOC/A-LOC. However, oxygen uptake and exercise blood pressure, oxygen pulse, etc., may not be the main factors influencing G-LOC/A-LOC.Lan X, Zhu W, Du J, Wang J, Yang M, Xu Y, Cao Y. High G tolerance and cardiopulmonary reserve function in healthy air force aviators. Aerosp Med Hum Perform. 2023; 94(12):911-916.

Meta-Analysis of Long-Term Efficacy of Proliferative Diabetic Retinopathy Based on Intelligent Medical Treatment.

In order to solve some problems of subhealth and high chronic diseases, the diagnosis and treatment of value-added diabetic retinopathy are studied. In particular, diabetes, a high chronic disease, poses a great threat to people's health. With the continuous improvement of national health awareness, the medical field also begins to pay more attention to the diagnosis and treatment of value-added diabetic retinopathy. In order to improve the long-term treatment of value-added diabetic retinopathy through intelligent medical monitoring and systematic scientific efficacy analysis and evaluation, the purpose of this study is to explore how to effectively achieve the meta-analysis of long-term efficacy of proliferative diabetic retinopathy through intelligent medical treatment. Through the study of diabetic retinopathy, the system can help doctors to achieve unlimited further signs of parameter acquisition and transmission and build more mature after treatment of the results of the monitoring platform. At the same time, a conclusion based on vitrectomy was proposed to effectively improve the surgical efficacy of patients with proliferative diabetic retinopathy.

Understanding online self-directed learning using point of care information systems (POCIS): A plot study using a capability approach perspective.

PURPOSE OF THE STUDY: Understanding self-directed learning (SDL) when using point of care information systems (POCIS) can inform educational providers of the usefulness of the system for continuing medical education (CME). Sen's capability approach can offer a unique perspective to understand SDL, which considers the extent to which individual valued learning needs can be achieved. The aim of the study was to pilot the use of a questionnaire informed by the capability approach for understanding SDL when using POCIS in the context of CME. METHODS: A semi-structured questionnaire aligned to the capability approach (Capability Approach for SDL with POCIS Questionnaire - CA-SPQ) in the context of CME was developed and implemented with 200 users of a POCIS (BMJ Best Practice). RESULTS: The response rate was 92 and 78% of users considered that their valued outcomes were achieved and that they could apply their new learning to practice. The questionnaire had high content, face, and construct validity. CONCLUSION: The CA-SPQ can offer a practical instrument to provide data and useful information for understanding SDL, when using POCIS in the context of CME. It also has the potential for adaptation to other areas of medical education.

EnSite NavX mapping system guided implantation of a dual-chamber permanent pacemaker in a 41-year-old pregnant woman with a 4-year follow-up.

BACKGROUND: X-ray fluoroscopy has been the primary cardiac imaging modality in permanent pacemaker implantation (PPI) operations, but it inevitably results in radiation exposure for both operators and patients. Fluoroscopy is considered a contraindication, especially in certain circumstances, such as gestation, during which the fetus is most sensitive to radiation exposure. Therefore, measures to avoid radiation exposure are necessary, and a more safe and feasible approach is needed for this procedure. Since the EnSite NavX mapping system (ENMS) can create the required geometric contours of those relevant cardiac structures and chambers, it can be used as an alternative to X-ray fluoroscopy in PPI. In addition, because the displacement of atrial leads is a common complication of PPI, lead displacement may occur more readily without fluoroscopic guidance. Therefore, reliable measures are required to prevent leads from displacement. CASE INTRODUCTION: A 41-year-old woman at the 15th week of gestation was referred to our department with recurrent episodes of syncope and amaurosis fugax for 2 years. Holter monitoring showed sinus rhythm, Mobitz Type II atrioventricular block and high-grade atrioventricular block with ventricular arrest up to 4945 ms. A dual-chamber PPI was performed successfully for the patient under the guidance of the ENMS instead of fluoroscopy. Displacement of atrial lead was effectively avoided by bending the top of atrial lead before implantation and making it a U-shape during operation, which left space for possible subsequent external pulling stress. CONCLUSIONS: For PPI, ENMS is a feasible and reliable alternative to traditional X-ray fluoroscopy, especially when performing operations on pregnant patients. By bending the top of the active-fixation atrial lead into a U-shape during operation, the displacement of atrial lead may be avoided.

Germline Mutation of PLCD1 Contributes to Human Multiple Pilomatricomas through Protein Kinase D/Extracellular Signal-Regulated Kinase1/2 Cascade and TRPV6.

Pilomatricoma, a benign skin appendage tumor, also known as calcifying epithelioma, consists of islands of epithelial cells histologically that contain anucleated cells in the center surrounded by basophilic cells and partial calcification. Sporadic pilomatricomas commonly have somatic mutations in the gene CTNNB1, but causative genes from germline and the underlying pathophysiology are unclear. In this study, we identified a germline missense variant of PLCD1 encoding PLCδ1, c.1186G>A (p.Glu396Lys), in a large Chinese family with autosomal dominant multiple pilomatricomas. Phospholipase C, a key enzyme playing critical roles in intracellular signal transduction, is essential for epidermal barrier integrity. The p.Glu396Lys variant increased the enzymatic activity of PLCδ1, leading to protein kinase C/protein kinase D/extracellular signal-regulated kinase1/2 pathway activation and TPRV6 channel closure, which not only resulted in excessive proliferation of keratinocytes in vitro and in vivo but also induced local accumulation of calcium in the pilomatricoma-like tumor that developed spontaneously in the skin of Plcd1E396K/E396K mice. Our results implicate this p.Glu396Lys variant of PLCD1 from germline leading to gain-of-function of PLCδ1 as a causative genetic defect in familial multiple pilomatricomas.

Explicit computational model of dielectric elastomeric lenses: erratum.

An erratum is presented to correct equation (8) in [Opt. Express25(23), 28710 (2017).10.1364/OE.25.028710].

[Preparation and in vitro evaluation of tissue engineered osteochondral integration of multi-layered scaffold].

Objective: The tissue engineered osteochondral integration of multi-layered scaffold was prepared and the related mechanical properties and biological properties were evaluated to provide a new technique and method for the repair and regeneration of osteochondral defect. Methods: According to blend of different components and proportion of acellular cartilage extracellular matrix of pig, nano-hydroxyapatite, and alginate, the osteochondral integration of multi-layered scaffold was prepared by using freeze-drying and physical and chemical cross-linking technology. The cartilage layer was consisted of acellular cartilage extracellular matrix; the middle layer was consisted of acellular cartilage extracellular matrix and alginate; and the bone layer was consisted of nano-hydroxyapatite, alginate, and acellular cartilage extracellular matrix. The biological and mechanics characteristic of the osteochondral integration of multi-layered scaffold were evaluated by morphology observation, scanning electron microscope observation, Micro-CT observation, porosity and pore size determination, water absorption capacity determination, mechanical testing (compression modulus and layer adhesive strength), biocompatibility testing [L929 cell proliferation on scaffold assessed by MTT assay, and growth of green fluorescent protein (GFP)-labeled Sprague Dawley rats' bone marrow mesenchumal stem cells (BMSCs) on scaffolds]. Results: Gross observation and Micro-CT observation showed that the scaffolds were closely integrated with each other without obvious discontinuities and separation. Scanning electron microscope showed that the structure of the bone layer was relatively dense, while the structure of the middle layer and the cartilage layer was relatively loose. The pore structures in the layers were connected to each other and all had the multi-dimensional characteristics. The porosity of cartilage layer, middle layer, and bone layer of the scaffolds were 93.55%±2.90%, 93.55%±4.10%, and 50.28%±3.20%, respectively; the porosity of the bone layer was significantly lower than that of cartilage layer and middle layer ( P<0.05), but no significant difference was found between cartilage layer and middle layer ( P>0.05). The pore size of the three layers were (239.66±35.28), (153.24±19.78), and (82.72±16.94) µm, respectively, showing significant differences between layers ( P<0.05). The hydrophilic of the three layers were (15.14±3.15), (13.65±2.98), and (5.32±1.87) mL/g, respectively; the hydrophilic of the bone layer was significantly lower than that of cartilage layer and middle layer ( P<0.05), but no significant difference was found between cartilage layer and middle layer ( P>0.05). The compression modulus of the three layers were (51.36±13.25), (47.93±12.74), and (155.18±19.62) kPa, respectively; and compression modulus of the bone layer was significantly higher than that of cartilage layer and middle layer ( P<0.05), but no significant difference was found between cartilage layer and middle layer ( P>0.05). The osteochondral integration of multi-layered scaffold was tightly bonded with each layer. The layer adhesive strength between the cartilage layer and the middle layer was (18.21±5.16) kPa, and the layer adhesive strength between the middle layer and the bone layer was (16.73±6.38) kPa, showing no significant difference ( t=0.637, P=0.537). MTT assay showed that L929 cells grew well on the scaffolds, indicating no scaffold cytotoxicity. GFP-labeled rat BMSCs grew evenly on the scaffolds, indicating scaffold has excellent biocompatibility. Conclusion: The advantages of three layers which have different performance of the tissue engineered osteochondral integration of multi-layered scaffold is achieved double biomimetics of structure and composition, lays a foundation for further research of animal in vivo experiment, meanwhile, as an advanced and potential strategy for osteochondral defect repair.

Responses of the Toll-like receptor and melanoma differentiation-associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks.

Avian infectious bronchitis virus (IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) ß (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ε, IKKα, IKKß, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-ĸB), IFN-α, IFN-ß, various interleukins(ILs), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.

[Nasal endoscopy-assisted bulboprostatic anastomosis for posterior urethral stricture].

OBJECTIVE: To study the clinical value and operation skills of nasal endoscopy-assisted bulboprostatic anastomosis in the treatment of posterior urethral stricture. METHODS: Between January 2012 and November 2014, we performed nasal endoscopy-assisted bulboprostatic anastomosis for 12 male patients with posterior urethral stricture. We recorded the operation time, blood loss, exposure of operation visual field, and success rate of anastomosis and summarized the operation skills. RESULTS: Eight of the patients experienced first-stage recovery. Two underwent a urethral dilation at 3 months postoperatively, 1 received 10 urethral dilations within 5 months after surgery, and 1 underwent internal urethrotomy after failure in urethral dilation, but all the 4 cases were cured. CONCLUSION: Nasal endoscopy can significantly improve the operation field exposure, elevate the precision, reduce the difficulty, and enhance the efficiency of bulboprostatic anastomosis in the treatment of posterior urethral stricture.

Calcification of the intervertebral disc and posterior longitudinal ligament in children.

STUDY DESIGN: Case report. OBJECTIVE: To report the clinical features, radiographic findings, treatments, and results of 2 children with cervical intervertebral disc calcification combined with ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The calcification of the intervertebral disc, which is more frequent in males with predominant localization to cervical spine, was first reported by Baron in 1924. OPLL of the cervical spine, which is found approximately in the 5th to 7th decade of life, is a disease-causing spinal canal stenosis and spinal cord compression. The etiologies of these 2 diseases still remain unclear. METHODS: An 8-year-old girl presented with progressive neck pain and complained of weakness and numbness of the upper left extremity, and a 6-year-old boy presented with complains of neck pain. X-ray, computed tomography, and magnetic resonance imaging findings of 2 patients confirmed the presence of cervical intervertebral disc calcification combined with OPLL. RESULTS: Two children were treated using conservative treatment. The girl was observed up for 2 years and the boy was observed up for 18 months, respectively. Computed tomography and magnetic resonance imaging revealed that cervical intervertebral disc calcification and OPLL at the C6/7 (case 1) and C3/4 (case 2) level have disappeared completely, only a small calcification at the C2/3 intervertebral disc remained in the second case and both of them were asymptomatic. CONCLUSIONS: Cervical intervertebral disc calcification combined with OPLL was rarely observed in children. Conservative management was carried out and the patients had a full recovery. Our experience suggests that the conservative treatment is an acceptable method.

Dynamic alteration of adiponectin/adiponectin receptor expression and its impact on myocardial ischemia/reperfusion in type 1 diabetic mice.

The present study determined the dynamic change of adiponectin (APN, a cardioprotective adipokine), its receptor expression, and their impact upon myocardial ischemia/reperfusion (MI/R) injury during type 1 diabetes mellitus (T1DM) progression, and involved underlying mechanisms. Diabetic state was induced in mice via multiple intraperitoneal injections of low-dose streptozotocin. The dynamic change of plasma APN concentration and cardiac APN receptor-1 and -2 (AdipoR1/2) expression were assessed immediately after diabetes onset (0 wk) and 1, 3, 5, and 7 wk thereafter. Indicators of MI/R injury (infarct size, apoptosis, and LDH release) were determined at 0, 1, and 7 wk of DM duration. The effect of APN on MI/R injury was determined in mice subjected to different diabetic durations. Plasma APN levels (total and HMW form) increased, whereas cardiac AdipoR1 expression decreased early after T1DM onset. With T1DM progression, APN levels were reduced and cardiac AdipoR1 expression increased. MI/R injury was exacerbated with T1DM progression in a time-dependent manner. Administration of globular APN (gAD) failed to attenuate MI/R injury in 1-wk T1DM mice, while an AMP-activated protein kinase (AMPK) activator (AICAR) reduced MI/R injury. However, administration of gAD (and AICAR) reduced infarct size and cardiomyocyte apoptosis in 7-wk T1DM mice. In conclusion, our results demonstrate a dynamic dysfunction of APN/AdipoR1 during T1DM progression. Reduced cardiac AdipoR1 expression and APN concentration may be responsible for increased I/R injury susceptibility at early and late T1DM stages, respectively. Interventions bolstering AdipoR1 expression during early T1DM stages and APN supplementation during advanced T1DM stages may potentially reduce the myocardial ischemic injury in diabetic patients.

Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes.

Apelin, a cytokine mainly secreted by adipocytes, is closely related with insulin resistance. The underlying molecular mechanisms of how apelin affects insulin resistance, however, are poorly understood. This study aimed to investigate the effect of apelin on glucose metabolism and insulin resistance in 3T3-L1 adipocytes. After 10 ng/ml TNF-α treatment for 24 h, insulin-stimulated glucose uptake was reduced by 47% in 3T3-L1 adipocytes. Apelin treatment improved glucose uptake in a time- and dose-dependent manner. Treatment of 1,000 nM apelin for 60 min maximally augmented glucose uptake in insulin-resistant 3T3-L1 adipocytes. Furthermore, apelin pre-incubation also increased adipocytes' insulin-stimulated glucose uptake, and PI3K/Akt pathway were involved in these effects. In addition, immunocytochemistry staining and western blotting analysis indicated that apelin could increase glucose transporter 4 translocation from the cytoplasm to the plasma membrane. Apelin also increased the anti-inflammatory adipokine adiponectin mRNA expression while reducing that of pro-inflammatory adipokine interleukin-6 in insulin-resistant 3T3-L1 adipocytes. These results suggest that apelin stimulates glucose uptake through the PI3K/Akt pathway, promotes GLUT4 translocation from the cytoplasm to the plasma membrane, and modulates inflammatory responses in insulin-resistant 3T3-L1 adipocytes.