Different treatment modalities on the prognosis of patients with stage I-IIIa small cell lung cancer: a population based study.

Background: Several studies have shown that surgery may improve prognosis in patients with limited-stage small cell lung cancer (LS-SCLC). This study aimed to compare the effects of different treatment modalities on lung cancer specific survival (LCSS) and overall survival (OS) in LS-SCLC patients. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with LS-SCLC. Kaplan-Meier analysis was used to determine the effect of each factor on LCSS and OS. Multivariate analysis was used to analyze the relationship between patient characteristics and survival of different treatment modalities. Results: After a series of screening steps, this study ultimately analyzed the prognosis of patients with stage I-IIIa SCLC under different treatment modalities. The results showed that lobectomy plus postoperative chemoradiotherapy was significantly better than chemoradiotherapy or lobectomy in treatment (all P<0.05). For stage II and IIIA patients, lobectomy plus postoperative chemotherapy ± radiotherapy had similar efficacy to chemoradiotherapy in improving patients' LCSS and OS (all P>0.05), and lobectomy plus postoperative chemotherapy ± radiotherapy did not significantly improve LCSS or OS compared with lobectomy (all P>0.05). Conclusions: For stage II-IIIa SCLC patients, lobectomy might have similar efficacy to chemoradiotherapy in improving LCSS and OS, and there is no need for adjuvant chemotherapy ± radiotherapy after surgery. For stage I SCLC patients, lobectomy plus postoperative chemoradiotherapy might be superior to chemoradiotherapy or lobectomy in improving LCSS and OS; however, the conclusion might be biased. These results suggest that the effect of surgery on SCLC patients may be worthy of further study.

The value of folate receptor-positive circulating tumour cells as a diagnostic biomarker for lung cancer: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the diagnostic value of folate receptor-positive (FR+) circulating tumour cells (CTCs) as a potential tumour marker for lung cancer diagnosis. METHODS: The PubMed, Embase, and Web of Science databases were searched for relevant articles published between database inception and November 2022. Eligible studies were selected based on inclusion and exclusion criteria. Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) were pooled with 95% confidence intervals (CI), using RevMan 5.4 and STATA 17.0 software to assess the diagnostic value of FR+CTC for lung cancer. RESULTS: After screening, 11 studies involving 3469 subjects were eligible for inclusion. The pooled sensitivity and specificity were 0.79 (95% CI 0.76, 0.82) and 0.84 (95% CI 0.81, 0.96), respectively, and the pooled positive and negative likelihood ratios were 4.90 (95% CI 4.25, 5.65) and 0.25 (95% CI 0.22, 0.29), respectively. The pooled diagnostic odds ratio was 19.70 (95% CI 16.06, 24.16). The AUC of the pooled summary receiver operating characteristic curve was 0.89 (95% CI 0.85, 0.91). Sensitivity analysis showed that this result was stable after one-by-one study elimination. CONCLUSION: Folate receptor-positive CTCs may have good diagnostic value in lung cancer.

Understanding vaccine hesitancy with PCV13 in children: Results of a survey in Shanghai, China.

A questionnaire survey for parents of children under 5 years of age was conducted to analyze vaccine hesitancy with the 13-valent pneumococcal conjugate vaccine (PCV13) in Shanghai, China. A total of 892 valid questionnaires were collected. Descriptive statistical methods, Chi-square test and effect size of Cohen were used. Among participants, 421 (48.8%) had children who had been vaccinated with PCV13 before the survey while 227 (26.73%) planned vaccination with PCV13 in the future. The main reasons for not receiving vaccination were the fear of adverse reactions (79, 26.7%), beyond vaccination age (69, 23.3%), and no need to vaccinate (44, 14.9%). Reducing vaccine hesitancy and increasing vaccination willingness can be achieved through health interventions, lower vaccine prices, and the adjustment of vaccination strategies.

Epidemiological characteristics and trends of Bacillus Calmette-Guérin lymphadenitis in Shanghai, China from 2010 to 2019.

Although the administration of the Bacillus Calmette-Guérin (BCG) vaccine is generally safe, lymphadenitis, the most common complication of BCG vaccination, can occur. Here, we describe the epidemiological characteristics and incidence trends of BCG lymphadenitis in Shanghai, China, among a population with a high burden of tuberculosis. A total of 56 cases of adverse events following immunization (AEFI) after BCG vaccination were reported in Shanghai, including 51 cases of BCG lymphadenitis (91.07%), from 2010 to 2019. The general incidence of BCG lymphadenitis was 173 per 1,000,000 doses in Shanghai from 2010 to 2019. A nonsignificant increase of 58.81% per year was observed between 2010 and 2012 (t = 0.93; p = .40), followed by a significant decline of 28.00% per year from 2012 to 2019 (t = -4.27; p < .01). Seven batches of BCG vaccines triggered three or more BCG lymphadenitis cases, for 27 (52.94%) cases in total. We identified two patients with immunodeficiency of chronic granulomatous disease, one of whom died four years later after BCG vaccination and another of whom was still being treated after two transplants. The average total care cost of the 47 recovered cases was 11,336 RMB (range: 2,637-33,861 RMB). Due to the high burden of BCG lymphadenitis, especially in children with immunodeficiency, it is suggested that government departments should strengthen healthcare provider training, assign specific nurses to perform BCG vaccination, monitor vaccinated individuals actively and timely detect abnormal signals so as to reduce the incidence of BCG lymphadenitis.

Low vaccination coverage of pneumococcal conjugate vaccines (PCVs) in Shanghai, China: A database analysis based on birth cohorts from 2012 to 2020.

BACKGROUND: Pneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage. METHODS: Vaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed. RESULTS: The total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020. CONCLUSIONS: Despite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.

Suppression effect of N-acetylcysteine on bone loss in ovariectomized mice.

Oxidative stress can trigger DNA damage response and activation of cellular senescence. Accumulating studies have demonstrated that senescent cells can produce senescence-associated secretory phenotype that leads to increased bone resorption and decreased bone formation. And elimination of senescent cells or inhibition of SASP secretion has been shown to prevent bone loss in mice. N-acetylcysteine (NAC) is a strong antioxidant. However, it is unclear whether reversed estrogen deficiency-induced bone loss by antioxidant NAC was associated with the inhibition of oxidative stress, DNA damage, osteocyte senescence and SASP. In this study, OVX mice were supplemented with/without E2 or NAC, and were compared with each other. Our results showed that oxidative stress, DNA damage, osteocyte senescence and the secretion of senescence-associated inflammatory cytokines were increased in OVX mice compared with sham-operated mice. However, these parameters were obviously rescued in OVX mice supplemented with E2 or NAC. Data from this study suggest that NAC can prevent OVX-induced bone loss by inhibiting oxidative stress, DNA damage, cell senescence and the secretion of the senescence-associated secretory phenotype.

Disulfiram/copper markedly induced myeloma cell apoptosis through activation of JNK and intrinsic and extrinsic apoptosis pathways.

Disulfiram (DSF) is an FDA approved anti-alcoholism drug in use for more than 60 years. Recently, antitumor activity of the DSF/copper (DSF/Cu) complex has been identified. Its anti-multiple myeloma activity, however, has barely been investigated. In the present study, our results demonstrated that the DSF/Cu complex induced apoptosis of MM cells and MM primary cells. The results indicated that DSF/Cu significantly induced cell cycle arrest at the G2/M phase in MM.1S and RPMI8226 cells. Moreover, JC-1 and Western blot results showed that DSF/Cu disrupted mitochondrial membrane integrity and cleaved caspase-8 in MM cells, respectively, suggesting that it induced activation of extrinsic and intrinsic apoptosis pathways. Interestingly, DSF/Cu induced caspase-3 activation was partly blocked by Z-VAD-FMK (zVAD), a pan-caspase inhibitor, indicating at caspase-dependent and -independent paths involved in DSF/Cu induced myeloma cell apoptosis machinery. Additionally, activation of the c-Jun N-terminal kinase (JNK) signaling pathway was observed in DSF/Cu treated MM cells. More importantly, our results demonstrated that DSF/Cu significantly reduced tumor volumes and prolonged overall survival of MM bearing mice when compared with the controls. Taken together, our novel findings showed that DSF/Cu has potent anti-myeloma activity in vitro and in vivo highlighting valuable clinical potential of DSF/Cu in MM treatment.

The long-term therapeutic effects of His-Purkinje system pacing on bradycardia and cardiac conduction dysfunction compared with right ventricular pacing: A systematic review and meta-analysis.

AIMS: His-Purkinje system pacing has been demonstrated as a synchronized ventricular pacing strategy via pacing His-Purkinje system directly, which can decrease the incidence of adverse cardiac structure alteration compared with right ventricular pacing (RVP). The purpose of this meta-analysis was to compare the effects of His-Purkinje system pacing and RVP in patients with bradycardia and cardiac conduction dysfunction. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases up to 15 December 2019. Studies on long-term clinical outcomes of His-Purkinje system pacing and RVP were included. Chronic paced QRS duration, chronic pacing threshold, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), all-cause mortality, and heart failure hospitalization were collected for meta-analysis. RESULTS: A total of 13 studies comprising 2348 patients were included in this meta-analysis. Compared with RVP group, patients receiving His-Purkinje system pacing showed improvement of LVEF (mean difference [MD], 5.65; 95% confidence interval [CI], 4.38-6.92), shorter chronic paced QRS duration (MD, - 39.29; 95% CI, - 41.90 to - 36.68), higher pacing threshold (MD, 0.8; 95% CI, 0.71-0.89) and lower risk of heart failure hospitalization (odds ratio [OR], 0.65; 95% CI, 0.44-0.96) during the follow-up. However, no statistical difference existed in LVEDV, LVESV and all-cause mortality between the two groups. CONCLUSION: Our meta-analysis suggests that His-bundle pacing is more suitable for the treatment of patients with bradycardia and cardiac conduction dysfunction.

A novel diagnostic method for pituitary adenoma based on magnetic resonance imaging using a convolutional neural network.

PURPOSE: This study was designed to develop a computer-aided diagnosis (CAD) system based on a convolutional neural network (CNN) to diagnose patients with pituitary tumors. METHODS: We included adult patients clinically diagnosed with pituitary adenoma (pituitary adenoma group), or adult individuals without pituitary adenoma (control group). After pre-processing, all the MRI data were randomly divided into training or testing datasets in a ratio of 8:2 to create or evaluate the CNN model. Multiple CNNs with the same structure were applied for different types of MR images respectively, and a comprehensive diagnosis was performed based on the classification results of different types of MR images using an equal-weighted majority voting strategy. Finally, we assessed the diagnostic performance of the CAD system by accuracy, sensitivity, specificity, positive predictive value, and F1 score. RESULTS: We enrolled 149 participants with 796 MR images and adopted the data augmentation technology to create 7960 new images. The proposed CAD method showed remarkable diagnostic performance with an overall accuracy of 91.02%, sensitivity of 92.27%, specificity of 75.70%, positive predictive value of 93.45%, and F1-score of 92.67% in separate MRI type. In the comprehensive diagnosis, the CAD achieved better performance with accuracy, sensitivity, and specificity of 96.97%, 94.44%, and 100%, respectively. CONCLUSION: The CAD system could accurately diagnose patients with pituitary tumors based on MR images. Further, we will improve this CAD system by augmenting the amount of dataset and evaluate its performance by external dataset.

Hydrogen sulfide protects against high glucose­induced lipid metabolic disturbances in 3T3­L1 adipocytes via the AMPK signaling pathway.

Aberrant lipid metabolism contributes to the development of type 2 diabetes mellitus. The mechanisms by which hydrogen sulfide (H2S), an endogenous gasotransmitter, regulates lipid metabolism remain unclear. The aim of the present study was to investigate if the protective effects of H2S during high glucose (HG)­induced lipid accumulation in 3T3­L1 adipocytes may be mediated by AMP­activated protein kinase (AMPK). Triglyceride (TG) content and the production of H2S were determined using adipogenesis colorimetric assay kits and H2S synthesis methods. The levels of monocyte chemoattractant protein­1 and adiponectin were evaluated by ELISA. Total AMPK and phosphorylated AMPK levels were assessed by western blot analysis. HG increased the cellular level of TG and decreased H2S production in 3T3­L1 adipocytes. The H2S donor, sodium hydrosulfide (NaHS) protected against the HG­induced accumulation of TG in 3T3­L1 adipocytes. Furthermore, NaHS suppressed HG­induced TG accumulation by activating AMPK. Collectively, the findings of the present study suggested that HG induced lipid accumulation in 3T3­L1 adipocytes, and AMPK activation may underlie the lipid­lowering effects of H2S.

N6 -(2-hydroxyethyl)-adenosine from Cordyceps cicadae protects against diabetic kidney disease via alleviation of oxidative stress and inflammation.

This study investigated the kidney-protective ability of N6 -(2-hydroxyethyl)-adenosine (HEA) in alloxan-induced diabetic rats. Diabetes was induced in the rats by the administration of alloxan monohydrate (150 mg/kg, i.p) and treated with HEA for 6 weeks. Diabetic rats displayed marked increase in blood glucose, serum creatinine (Scr), and blood urea nitrogen (BUN), in addition to high excretion of urinary protein and albumin. Furthermore, diabetic rats showed decreased renal levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and increased malondialdehyde (MDA) as well as renal concentrations of pro-inflammatory mediators (TNF-α, IL-6, IL-1ß, and TGF-ß1). Treatment of diabetic rats with HEA (20 and 40 mg/kg) significantly increased the renal antioxidant level, reduced the levels of blood glucose, Scr, BUN, urinary protein, albumin, and pro-inflammatory mediators in a dose-dependent fashion. Histological evaluation of the kidney of diabetic rats indicated that HEA also ameliorated glomerular and tubular changes. PRACTICAL APPLICATIONS: HEA is a bioactive constituent isolated from Cordyceps cicadae and has been shown to possess antihyperglycemic, kidney protective, antioxidant, and antiinflammatory effects in diabetic rats. HEA stimulated the antioxidant enzymes' activities in the kidney tissues as well as reduced pro-inflammatory mediators, indicating its antidiabetic and renoprotective effects in diabetic models. The results showed that HEA attenuated oxidative stress and inflammation in kidney tissues.

Low glucagon-like peptide-1 (GLP-1) concentration in serum is indicative of mild cognitive impairment in type 2 diabetes patients.

OBJECTIVES: To reveal potential association between glucagon-like peptide 1 (GLP-1) concentration in serum and mild cognitive function impairment (MCI) in type 2 diabetes mellitus (T2DM) patients. PATIENTS AND METHODS: A total of 106 T2DM patients and 47 normal controls were recruited in this study. Montreal Cognitive Assessment (MoCA) was performed in all subjects. Among the 106 patients, 52 presented with MCI. Fasting blood glucose (FBG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), triglyceride (TG), uric acid (UA) and GLP-1 levels were also assessed in all subjects. RESULTS: Patients with MCI had higher serum concentrations of FBG and TC and lower concentrations of GLP-1 and HDL-C than controls. Bivariate correlation analysis showed that MCI in T2DM patients closely correlated with FBG, HDL-C, and GLP-1 levels. Moreover, ordinal regression analysis showed that GLP-1 concentration in serum was protective for MCI in T2DM patients (OR = 0.025; 95%CI: 0.005-3.934). CONCLUSIONS: Our results indicated that low concentration of GLP-1 may play a role in the pathogenesis of MCI in T2DM patients.

Higher non-HDL-cholesterol to HDL-cholesterol ratio linked with increased nonalcoholic steatohepatitis.

BACKGROUND: Non-HDL-cholesterol to HDL-cholesterol (non-HDL-c/HDL-c) ratio is a feasible predictor for coronary heart disease, metabolic syndrome, and insulin resistance. Patients with nonalcoholic steatohepatitis (NASH) have an increased risk of developing cardiovascular problems and type 2 diabetes. However, the predictive role of non-HDL-c/HDL-c ratio in NASH hasn't been investigated yet. METHODS: We conducted a retrospective cohort study. A total of 3489 eligible subjects were selected in the present study. Prevalence and characteristics of NASH were demonstrated. Conditional logistic regression was used to analyze the association between non-HDL-c/HDL-c ratio and risks of NASH. Associations between non-HDL-c/HDL-c ratio and serum aminotransferase levels were also investigated. RESULTS: The overall prevalence of NASH was 6.13%, higher in male (6.89%) than that in female (5.04%). Interestingly, the prevalence of NASH showed a positive correlation with the elevation of non-HDL-c/HDL-c ratio (Pearson's Chi-squared test, linear trend 0.010, p <  0.05). The risk of NASH increased approximately 1.8-fold among subjects with higher non-HDL-c/HDL-c ratio. After adjustment for confounding factors, higher non-HDL-c/HDL-c ratio was still associated with a 54.4% increased risk of NASH. Male had higher risk of NASH than female when their non-HDL-c/HDL-c ratio increased. The risk of NASH in subjects with BMI more than 24 was 3 times higher than that in subjects with BMI less than 24. Every one unit increase in Non-HDL-c/HDL-c ratio was associated with 64.5% increase in ALT/AST level (p <  0.05) after adjustment for confounding factors. CONCLUSIONS: Our study provided strong evidence that subjects with higher non-HDL-c/HDL-c ratio had a higher risk of NASH, which suggested that non-HDL-c/HDL-c ratio might be a feasible predictor for NASH.

NETosis may play a role in the pathogenesis of Hashimoto's thyroiditis.

Neutrophil extracellular traps (NETs) are shown to play important roles in the progression or development of systemic autoimmune diseases. However, implication of NETs or NETosis in the pathogenesis of non-systemic autoimmune diseases such as Hashimoto's thyroiditis (HT), a chronic inflammatory organ-specific autoimmune disease, has not been previously reported. In the present study, our results demonstrate that the concentration of NET products, neutrophil elastase (NE) and proteinase 3 (PR3) in plasma, are significantly higher in the patients with HT than in healthy controls, respectively. In addition, PR3 concentration in plasma was positively associated with the titers of autoantibodies against thyroglobulin (TGAb) and thyroid peroxidase (TPOAb) in serum, respectively. Consistently, NETosis was more markedly induced in neutrophils derived from the HT patients than controls. Concomitantly, IL-6 production in the NETosis induction system in the neutrophils from the patients was significantly higher than those in controls. Moreover, serum from HT patients but not healthy controls induced more pronounced NETosis in neutrophils. Meanwhile, our immuno-fluorescence staining results showed that NETs from the HT patients contained autoantigens. These findings together indicate roles for NETs and/or NETosis in autoantibody generation as well as pathogenesis of HT. Therefore, the underlying mechanisms of NETs in the pathogenesis of HT warrant further study.

Urinary Microvesicle-Bound Uromodulin: A Potential Molecular Biomarker in Diabetic Kidney Disease.

This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD.

Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway.

BACKGROUND: Obesity is closely related to the metabolism of triacylglycerol (TG) in adipocytes. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are rate-limiting enzymes that control the hydrolysis of TG. Effects on ATGL and HSL to increase lipolysis may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicine plant Coptis chinensis. In the present study we show the effects of BBR on ATGL and HSL and explore the potential underlying mechanisms of these effects. METHODS: The TG content in cells was measured using a colorimetric assay. The expressions of HSL, ATGL and GPAT3 were evaluated by Western-blotting. The expression of ATGL was also evaluated by real-time PCR and radioimmunoassay. Compound C, an inhibitor of AMP-activated protein kinase (AMPK), was used to explore the possible pathway that involved in the effect of BBR on ATGL. RESULTS: TG content of differentiated 3T3-L1 cells was significantly decreased by more than 10% after treated with BBR. In differentiated 3T3-L1 adipocytes, BBR increased the expression of p-HSL and ATGL, and these effects were time-depended (p <0.01). The effect of BBR on ATGL expression could be abolished by Compound C which suggested that AMPK pathway was involved in the effects of BBR on p-HSL and ATGL. CONCLUSIONS: BBR could increase the expression of ATGL and therefore stimulate basal lipolysis in mature adipocytes through the associated mechanisms related to the AMPK pathway.

Significance of vaspin in obstructive sleep apnea-hypopnea syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a commonly-diagnosed chronic sleep disorder. It is considered to be an important independent risk factor in the development of insulin resistance (IR). Patients with OSAHS exhibit a variety of metabolic disorders, including obesity and metabolic syndrome. Visceral adipose tissue-derived serpin (vaspin) is an adipokine that is considered to be a link between obesity and IR. The present study aimed to evaluate the levels of plasma vaspin in patients with OSAHS and examine their potential correlation with sleep characteristics. A total of 20 healthy male subjects and 42 male patients with OSAHS were selected, and patients were divided into mild (n=22) and severe (n=20) OSAHS groups. The 20 patients in the severe OSAHS group received nasal continuous positive airway pressure (nCPAP) treatment for 2 months. Venous blood samples were drawn from all patients in a fasting state prior to and subsequent to nCPAP treatment, which were used to measure the levels of biochemical indicators. The sleep parameters and serologic index changes were compared prior to and following treatment. The values of contractive pressure (SBP), neck circumference (NC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI) and hip circumference (HC) in the two OSAHS groups were significantly increased compared with those in the control group. In addition, the levels of vaspin in OSAHS patients were markedly increased and vaspin was revealed to be positively associated with fasting blood sugar, fasting insulin, triglycerides, homeostasis model assessment-IR, apnea-hypopnea index (AHI), NC, WC, BMI and WHR (P<0.05). After 2 months of nCPAP treatment, the SBP and AHI were significantly reduced. In conclusion, vaspin may have an important role in OSAHS patients with IR and treatment using nCPAP may improve the condition of OSAHS patients.

Changes of lipin1ß expression in gestational diabetes mellitus.

BACKGROUND: Lipin1ß is an adipokine proposed to be associated with insulin resistance (IR). Pregnancy is a physiologic state of progressive IR. The objective of the present study was to investigate the role of lipin1ß in the development of GDM. METHODS: A total of 40 pregnant women (22 normal and 18 with GDM) who delivered healthy infants at full-term (> 37 weeks gestation) were included. The mRNA and protein levels of lipin1ß in adipose tissues were determined by real-time RT-PCR and Western-blot. Plasma glucose, lipids, insulin, and estradiol (E2) levels were measured routinely at fasting state, and HOMA-IR was calculated accordingly. RESULTS: The lipin1ß expression in both mRNA and protein levels in SAT and VAT was lower in GDM patients than controls. Lipin1ß mRNA in VAT was negatively correlated with BMI (r = -0.505, p < 0.05), FINS (r = -0.539, p < 0.05), HOMA-IR (r = -0.574, p < 0.01), TG (r = -0.471, p < 0.05), and E2 (r = -0.564, p < 0.01). Lipin1ß mRNA expression in SAT was similar with VAT. Lipin1ß mRNA was not correlated with body weight gain or blood pressure. These results indicated that the lipin1ß expression in adipose tissues is down-regulated in patients with GDM. CONCLUSIONS: Lipin1ß might play a role in the pathogenesis of insulin resistance in GDM.

Laminin 411 acts as a potent inducer of umbilical cord mesenchymal stem cell differentiation into insulin-producing cells.

BACKGROUND: Diabetes mellitus (DM) is an incurable metabolic disease constituting a major threat to human health. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) hold great promise in the treatment of DM. The development of an efficient IPC induction system is a crucial step for the clinical application of IPCs for DM. Laminin 411 is a key component of the basement membrane and is involved in the regulation of cell differentiation; however, little is known about a role of laminin 411 in the regulation of IPC differentiation from human MSCs. METHODS: MSCs were isolated from human umbilical cord (UC-MSCs) and expanded in an in vitro culture system. UC-MSCs were then cultured in the IPC induction and differentiation medium in the presence of laminin 411. Flow cytometry, Quantitative realtime PCR, immunofluorescence staining, ELISA, Western blotting and other techniques were applied to determine IPC generation, insulin expression and related mechanisms. To evaluate potential therapeutic efficacy of IPCs induced from UC-MSCs, a type-1 diabetes (T1DM) rat model was generated using streptozotocin. Blood glucose, insulin levels, and survival of rats were monitored periodically following intravenous injection of the tested cells. RESULTS: Laminin 411 markedly induced the expression of the genes Foxa2 and Sox17, markers for pancreatic precursor cells, efficiently induced IPC differentiation from MSCs, and up-regulated insulin expression at both mRNA and protein levels. Furthermore, the expression of the genes known to govern insulin expression including Pdx1 and Ngn3 was markedly induced by laminin 411, which suggests that Pdx1 and Ngn3 signaling pathways are involved in laminin 411 induced-insulin expression machinery. More importantly, administration of laminin 411-induced IPCs rapidly and significantly down-regulated fasting blood glucose levels, significantly reduced the HbA1c concentration and markedly improved the symptoms and survival of T1DM rats. CONCLUSIONS: Our results demonstrate that laminin 411 acts as a potent differentiation inducer of IPCs from UC-MSCs via the Pdx1 and Ngn3 signaling pathways. Moreover, transfusion of laminin 411 induced-IPCs more efficiently improves symptoms and survival of T1DM rats. These novel finding highlights a potential clinical application of laminin 411 induced-IPCs in the treatment of T1DM, which calls for further studies.