Dietary inflammatory index and cardiorenal function in women with diabetes and prediabetes.

BACKGROUND AND AIMS: Previous studies had shed a new light on the importance of multiple inflammatory mechanisms in the pathogenesis of arterial stiffness. The dietary inflammatory index (DII®) is a new tool for estimating the overall inflammatory potential of the diet. The aim of this study is to assess the association of the inflammatory potential of diet with peripheral arterial stiffness and renal function in women with diabetes and prediabetes. METHODS AND RESULTS: This is an observational cross-sectional study. A total of 2644 females aged 45-75 years were included for the study. Dietary intake in the past 12 months was assessed by a validated China National Nutrition and Health Survey 2002 (CNHS2002) food-frequency questionnaire. Energy-adjusted DII (E-DII) scores were calculated from daily dietary information. In a multivariable linear regression analysis adjusted for potential confounders, E-DII was positively associated with brachial ankle pulse wave velocity (baPWV) in participants with diabetes (ß = 12.820; 95% CI = 2.565, 23.076; P = 0.014) and prediabetes (ß = 29.025; 95% CI = 1.110, 56.940; P = 0.042), but not in females with normal glucose homeostasis. In addition, per unit increase of E-DII was significantly associated with lower eGFR (ß = -1.363; 95% CI = -2.335, -0.392; P = 0.006) in patients with diabetes. CONCLUSION: We identified a direct association between E-DII and arterial stiffness, decreasedeGFR in middle-aged and elderly women with diabetes or prediabetes. Future studies are needed to verify and clarify the role of E-DII as an intervention target for cardiorenal complications of chronic hyperglycemia.

Identification of autoimmune type 1 diabetes and multiple organ-specific autoantibodies in adult-onset non-insulin-requiring diabetes in China: A population-based multicentre nationwide survey.

AIMS: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D). MATERIALS AND METHODS: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT. RESULTS: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001). CONCLUSIONS: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations.

Association between Depression and Renal Hyperfiltration in a General Chinese Population.

BACKGROUND: Depression is prevalent in patients with all stages of CKD and is associated with adverse outcome. Abnormally elevated GFR, or hyperfiltration, may play a crucial role in the initiation and progression of CKD. However, the association between depression and hyperfiltration is not known. The aim of this study is to investigate the relationship between depression and hyperfiltration. METHODS: This was an observational cross-sectional study. A total of 3,716 volunteers (1,303 males and 2,413 females) aged 40-75 years without CKD from a community in China were included for the study. Depressive symptoms and the presence of a minor or major depressive episode were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and Diagnostic and Statistical Manual of Mental Disorders (4th edition)-based structured interview, respectively. RESULTS: The mean age of the participants in the present study was 53.8 ± 9.0 years. 115 participants had clinically relevant depression, and 122 participants had a minor or major depressive episode. In a multivariable logistic regression analysis adjusted for potential confounders, the association between clinically relevant depression and renal hyperfiltration remained significant in men but not in women. As compared with men without depression (PHQ <5) or depressive episodes, those with clinically relevant depression (PHQ ≥10) had a significantly higher risk of renal hyperfiltration. The fully adjusted OR (95% CI) was 4.81 (1.62-14.30, p = 0.005), those with a major depressive episode had a higher risk of renal hyperfiltration (OR 7.45; 95% CI 2.04-27.21, p = 0.002). CONCLUSION: Depressive symptoms and major depressive episodes are associated with renal hyperfiltration in middle-aged and elderly Chinese men without CKD. Future studies are needed to verify and clarify the role of depression in the development of abnormally high eGFR and CKD.

EXPOSURE TO FAMINE IN EARLY LIFE AND THE RISK OF OSTEOPOROSIS IN ADULTHOOD: A PROSPECTIVE STUDY.

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood. Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more. Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (ß, -5.07 [-10.226, 0.127]) and BUA (ß, -4.321 [-0.88, 0.238]). The early- and mid-childhood-exposed cohorts had significantly lower QUI (ß, -7.085 [-11.799, -2.372] versus ß, -10.845 [-15.68, -6.01]) and BUA (ß, -6.381 [-10.515, -2.246] versus ß, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS. Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality. Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound.

RAGE Gly82Ser polymorphism in patients with type 2 diabetes with comorbid Depression.

OBJECTIVE: To examine receptors for advanced glycation end-products Gly82Ser polymorphism in patients of type 2 diabetes with comorbid depression. METHODS: The case-control study was conducted at Fujian Provincial Hospital, Fuzhou, China, between December 2011 and December 2012, and comprised unrelated Chinese Han patients of type 2 diabetes, and diabetics with diagnosed clinical depression. Gly82Ser polymorphism polymorphism was determined using polymerase chain reaction amplification-high resolution melting curve protocol. Serum levels of endogenous secretory receptor for advanced glycation end products were measured using enzyme-linked immunosorbent assay. SPSS 16 was used for data analysis. RESULTS: Of the 114 subjects, 72(63.15%) were clinically depressed. Lower levels of endogenous secretory receptor were found in the depression group compared with the other group (p=0.049). No difference in genotypes or allele frequencies existed between the two groups (p>0.05). Gly82Ser carriers had significantly higher Hamilton Rating Scale scores (p<0.001) and lower serum endogenous secretory receptor (p=0.012) among the depressed diabetics. There were also significant differences in body mass index (p=0.005), abdominal circumference (p=0.038), carotid intima-media thickness (p=0.037) and high-sensitivity C-reactive protein (p=0.005) concentration between the different genotypes.. CONCLUSIONS: Receptors for advanced glycation end-products-ligands system may be involved in type 2 diabetes with comorbid depression at the genetic level.

Self-reported sleep duration and daytime napping are associated with renal hyperfiltration in general population.

STUDY OBJECTIVES: Renal hyperfiltration (RHF) has emerged as a novel marker of early renal damage in various conditions such as diabetes and metabolic syndrome. Aberrant sleep duration and excessive daytime napping may affect the development of chronic kidney disease (CKD). In this study, the association between sleep duration, daytime napping, and renal hyperfiltration was assessed. SETTING: This study was conducted in three communities in China. PARTICIPANTS: A total of 16,119 community volunteers (5735 males and 10,384 females) aged 40-65 years without CKD were included for the study. METHODS AND RESULTS: Participants with short sleep duration (<6 h/day) or long sleep duration (≥10 h/day) were at a significantly increased risk of renal hyperfiltration. The fully adjusted ORs (95% CI) were 2.112 (1.107, 4.031) and 2.071 (1.504, 2.853), respectively (P < 0.05). In addition, those who took naps longer than 1.5 h per day had a higher risk of renal hyperfiltration compared with those without napping (OR 1.400, 95% CI 1.018-1.924). Further joint analysis indicated that participants with long sleep duration (≥10 h/day) had a more than twofold increased risk of RHF regardless of nap status compared with those who slept 8-9 h per day without daytime napping. The association between sleep duration or daytime napping and RHF could not be explained by the influence of sleep quality. Additional subgroup analysis showed long sleep duration (≥9 h/day) and long daytime napping (≥1.5 h) were associated with an increased risk of RHF among individuals with good sleep quality. CONCLUSION: Sleep duration less than 6 h/day or more than 10 h/day and long daytime napping tend to be associated with an increased risk of renal hyperfiltration in middle-aged general population, and this relationship was independent of diabetes, hypertension, obesity, or poor sleep quality.

Effect of Hypoxia on Self-Renewal Capacity and Differentiation in Human Tendon-Derived Stem Cells.

BACKGROUND Hypoxic conditions play roles in functioning of human tendon-derived stem cells (hTSCs). The goal of this study was to investigate the effect of various hypoxic conditions in self-renewal capacity and differentiation of TSCs. MATERIAL AND METHODS hTSCs was obtain from supraspinatus tendon donors. Colony formation and cell proliferation assay were used to assess the self-renewal of hTSCs. qRT-PCT and Western blot analysis were used to examine stemness and multi-differentiation potential of hTSCs. RESULTS We found that culturing at 5% O2 is more beneficial for the self-renewal of hTSCs than the other 3 culture conditions, with larger colony size and numbers. The proliferation of hTSCs in 5%, 10%, and 20% O2 cultures increased after seeding. The number of cells in the 5% O2 condition was higher than that in other culture; however, self-renewal capacity of hTSCs in 0.5% O2 was inhibited. The expression levels of stem cell markers, including NS, Nanog, Oct-4, and SSEA-4, were highest in 0.5% O2 culture. Furthermore, hTSCs cultured in 20% O2 exhibited significantly higher expression of the 3 markers (PPAR-γ, Sox-9, and Runx-2). CONCLUSIONS Hypoxic condition of culture encouraged self-renewal capacity of hTSCs, but inhibited their multi-differentiation potential, compared to normoxic condition of culture. Moreover, excessively low oxygen concentration impaired the capacity of hTSCs.

Comparison of proximal femoral nail antirotation internal fixation and artificial hip replacement for elderly patients with intertrochanteric fractures.

OBJECTIVE: To compare the effects of proximal femoral nail antirotation (PFNA) internal fixation and artificial hip replacement (AHR) on serum inflammatory factors and hip function recovery in elderly patients with intertrochanteric fractures (IFs). METHODS: One hundred and thirty patients with IFs who underwent surgery at the People's Hospital of Pingyang between July 2018 and July 2020 were enrolled. Sixty-five patients received PFNA internal fixation (fixation group) and 65 received AHR (replacement group). Surgical indicators and complications were recorded in both groups. The Harris Hip Scale was used to score hip joint function, the Visual Analog Scale (VAS) to assess pain, the MOS 36-Item Short-Form Health Survey (SF-36) to evaluate life quality, and enzyme-linked immunosorbent assay to measure serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß. RESULTS: The replacement group experienced notably shorter hospitalization times, less complete weight-bearing time, and earlier time to walk compared to the fixation group (all P<0.05). The replacement group also showed a lower incidence of poor fracture healing and complications (both P<0.05). Additionally, on postoperative days 3, 15, and 45, the replacement group had notably lower VAS scores (all P<0.05). Furthermore, the replacement group exhibited higher Harris Hip Scale scores at 1, 2, and 3 months post-surgery (all P<0.05). Higher postoperative SF-36 scores were also observed in the replacement group (P<0.05). On postoperative day 30, both groups presented decreases in TNF-α, IL-6, and IL-1ß levels compared to preoperative levels, with even lower levels in the replacement group (all P<0.05). CONCLUSIONS: AHR can help elderly patients with IFs ambulate earlier, speed up hip function recovery, reduce inflammation, and improve life quality with fewer postoperative complications, making it worthy of clinical promotion.

Serum lipids and lipoproteins in Chinese men and women.

BACKGROUND: Because of rapid change in lifestyle risk factors, cardiovascular disease has become the leading cause of death in China. We sought to estimate the national levels of serum lipids and lipoproteins among the Chinese adult population. METHODS AND RESULTS: We conducted a cross-sectional study in a nationally representative sample of 46 239 adults aged ≥20 years. Fasting serum total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglycerides were measured by standard methods. The age-standardized estimates of total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglycerides were 4.72 (95% confidence interval, 4.70-4.73), 1.30 (1.29-1.30), 2.68 (2.67-2.70), and 1.57 (1.55-1.58) mmol/L, respectively, in the Chinese adult population. In addition, 22.5% (21.8-23.3%) or 220.4 million (212.1-228.8) Chinese adults had borderline high total cholesterol (5.18-6.21 mmol/L), and 9.0% (8.5-9.5%) or 88.1 million (83.4-92.8) had high total cholesterol (≥6.22 mmol/L). The population estimates for borderline high (3.37-4.13 mmol/L), high (4.14-4.91 mmol/L), and very high (≥4.92 mmol/L) low-density lipoprotein cholesterol were 13.9% (13.3-14.5%) or 133.5 million (127.0-140.1), 3.5% (3.3-3.8%) or 33.8 million (31.2-36.5), and 3.0% (2.8-3.3%) or 29.0 million (26.3-31.8) persons, respectively. In addition, 22.3% (21.6-23.1%) or 214.9 million (207.0-222.8) persons had low high-density lipoprotein cholesterol (<1.04 mmol/L). The awareness, treatment, and control of borderline high or high total cholesterol were 11.0%, 5.1%, and 2.8%, respectively, in the Chinese adult population. CONCLUSIONS: Serum total and low-density lipoprotein cholesterol levels were high and increasing in the Chinese population. Without effective intervention, atherosclerotic cardiovascular diseases may soar in the near future in China.

Prevalence of diabetes among men and women in China.

BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed.

Prognostic significance of circulating tumor cell measurement in the peripheral blood of patients with nasopharyngeal carcinoma.

OBJECTIVE: Nasopharyngeal Carcinoma (NPC) is lethal cancer. Typically, relapse and metastasis are the outcomes of most patients. Against this backdrop, this study aimed to investigate the correlation between Circulating Tumor Cell (CTC) profiles and clinicopathological features in patients with NPC. PATIENTS AND METHODS: A total of 119 blood samples from 79 patients were collected from patients with NPC during treatment. CanPatrolTM CTC enrichment and RNA In Situ Hybridization (RNA-ISH) were used to characterize CTCs, including epithelial, Mesenchymal (MCTCs), and epithelial/mesenchymal mixed types according to their surface markers. RESULTS: The number of CTCs and MCTCs in the pre-treatment group was significantly higher than that in the post-treatment group (p < 0.05). The total number of CTCs and MCTCs cell numbers was significant correlation with Tumor-Node-Metastasis (TNM) staging (p < 0.05), Progression-Free Survival (PFS), and Overall Survival (OS). The PFS of patients with > 7 CTCs or > 5 MCTCs per 5 mL blood was significantly shorter PFS than those patients with ≤ 7 CTCs or ≤ 5 MCTCs (p < 0.05). Patients treated with targeted therapy combined with chemoradiotherapy had poorer PFS and OS rates than those treated with chemoradiotherapy (p < 0.05). The Kaplan-Meier survival analysis also demonstrated that patients with changes in CTC > 4 were strongly associated with PFS and OS rates (p < 0.05). CONCLUSION: CTC and MCTC number detection in patients with NPC is a useful biomarker for predicting patient progress. Patients with more than 7 CTCs or 5 MCTCs in 5 mL of blood had shorter PFS and OS rates. CTC and MCTC count changes were also significantly associated with the patient's therapy.

Circ_0006873 Sponges miR-142-5p to Inhibit Osteoblastic Differentiation of hBMSCs via Regulating PTEN/Akt Signaling Pathway.

OBJECTIVE: Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation may serve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 on osteoporosis. METHODS: Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expression data. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools (starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression, cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP) staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expression of RNAs and proteins after transfection or during osteoblastic differentiation. RESULTS: circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experiments revealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblastic differentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 sponged miR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescue assay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenic markers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTEN to inhibit osteoblastic differentiation. CONCLUSION: Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulation of Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.

[Expression, purification, and characterization of cell-permeable fusion antioxidant enzyme sensitive to matrix metalloproteinases-2/9].

Antioxidant enzymes fused with cell-penetrating peptides could enter cells and protect cells from irradiation damage. However, the unselective transmembrane ability of cell-penetrating peptide may also bring antioxidant enzymes into tumor cells, thus protecting tumor cells and consequently reducing the efficacy of radiotherapy. There are active matrix metalloproteinase (MMP)-2 or MMP-9 in most tumor cellular microenvironments. Therefore, a fusion protein containing an MMP-2/9 cleavable substrate peptide X, a cell-penetrating peptide R9, a glutathione S-transferase (GST), and a human Cu, Zn superoxide dismutase (SOD1), was designed and named GST-SOD1-X-R9. In the tumor microenvironment, GST-SOD1-X-R9 would lose its cell-penetrating peptide and could not enter tumor cells due to the cleavage of substrate X by active MMP-2/9, thereby achieving selected entering normal cells. The complete nucleotide sequence of SOD1-X-R9 was synthesized and inserted into the prokaryotic expression vector pGEX-4T-1. The pGEX4T-1-SOD1-X-R9 recombinant plasmid was obtained, and soluble expression of the fusion protein was achieved. GST-SOD1-X-R9 was purified by ammonium sulfate precipitation and GST affinity chromatography. The molecular weight of the fusion protein was approximately 47 kDa, consistent with the theoretical value. The SOD and GST activities were 2 954 U/mg and 328 U/mg, respectively. Stability test suggested that almost no change in either SOD activity or GST activity of GST-SOD1-X-R9 was observed under physiological conditions. The fusion protein could be partially digested by collagenase Ⅳ in solution. Subsequently, the effect of MMP-2/9 activity on transmembrane ability of the fusion protein was tested using 2D and 3D cultured HepG2 cells. Little extracellular MMP-2 activity of HepG2 cells was observed under 2D culture condition. While under the 3D culture model, the size and the MMP-2 activity of the HepG2 tumor spheroid increased daily. GST-SOD1-R9 proteins showed the same transmembrane efficiency in 2D cultured HepG2 cells, but the transmembrane efficiency of GST-SOD1-X-R9 in 3D cultured HepG2 spheres was reduced remarkably. This study provided a basis for further investigating the selectively protective effect of GST-SOD1-X-R9 against oxidative damage in normal cells.

The effect of NF-κB pathway on proliferation and apoptosis of human umbilical vein endothelial cells induced by intermittent high glucose.

Our previous study found that blocking nuclear factor (NF)-κB signaling could protect human umbilical vein endothelial cells (HUVECs) from apoptosis and proliferation inhibition due to high glucose (HG). Intermittent HG makes glucose toxicity more significant. In this study, we aimed to investigate the effect of NF-κB pathway on HUVECs induced by intermittent HG (a daily alternating 5.5 or 30.5 mmol/l glucose). A recombinant adenovirus containing a RNAi cassette targeting the NF-κB/p65 gene was produced, and its silencing effect on p65 gene was detected by Western blot analysis in HUVECs cultured with intermittent HG. The subsequent effect on proliferation of HUVECs in the indicated conditions was measured by the AlamarBlue assay. The Bcl-2 expression was also detected by Western blot. The results showed that the expression of p65 protein could be inhibited efficiently by the RNAi adenovirus. Intermittent HG also induced the translocation of NF-κB in HUVECs. Inhibition of NF-κB with the RNAi adenovirus could prevent the effects. At the 6th day after HUVECs were exposed to intermittent HG, the proliferation of HUVECs with Ad-1566 was significantly higher than that of HUVECs with Ad-DEST (P < 0.01). Knockdown of NF-κB/p65 up-regulated the Bcl-2 expression of HUVECs under intermittent HG conditions (P < 0.01). These findings concluded that the NF-κB/p65-targeting RNAi adenovirus is an important tool, which can efficiently inhibit the expression of p65 gene in HUVECs. Intermittent HG reduces HUVECs proliferation with a concomitant increase in apoptosis. Knockdown of NF-κB/p65 partly protected HUVECs from proliferation inhibition and may reduce apoptosis.

Construction of NF-κB-targeting RNAi adenovirus vector and the effect of NF-κB pathway on proliferation and apoptosis of vascular endothelial cells.

To construct a recombinant adenovirus vector expressing a RNAi for the Nuclear Factor kappa B (NF-κB)/p65 gene and use it to explore the role of the NF-κB pathway on the regulation of proliferation and apoptosis of vascular endothelial cells. A recombinant adenovirus containing a RNAi cassette targeting the p65 gene was constructed, and its silencing effect on p65 was detected by Western blot analysis in ECV304 cells. Expression of the p65 protein in ECV304 cells was efficiently down-regulated by the RNAi adenovirus for more than 6 days. ECV304 cells proliferation and apoptosis were measured using the MTT assay and flow cytometry, respectively. Blocking the NF-κB pathway with the RNAi adenovirus substantially decreased the proliferation of ECV304 cells, but only slightly affected cell apoptosis. We used a NF-κB/p65-targeting RNAi adenovirus to demonstrate the role of the NF-κB pathway in the regulation of ECV304 cell proliferation. This adenovirus may serve as an important tool to study the NF-κB pathway.

Globular adiponectin regulates energy homeostasis through AMP-activated protein kinase-acetyl-CoA carboxylase (AMPK/ACC) pathway in the hypothalamus.

Adiponectin is a newly researched adipokine which participates in the regulation of energy homeostasis. AMP-activated protein kinase (AMPK) represents an energy sensor that responds to hormone and nutrition status in vivo and exerts a regulatory effect in the hypothalamus and multiple peripheral tissues. We investigated the possible mechanisms involved in appetite regulation by adiponectin in vitro with GT1-7 cells, a mouse immortalized hypothalamic neuron. The results showed that adiponectin increased the phosphorylation of AMPK, activated AMPK phosphorylated and inactivated acetyl-CoA carboxylase (ACC), and subsequently increased expression of agouti-related peptide (AgRP) mRNA. Our results also indicated that adiponectin had no effect on signal transducer and activator of transcription (STAT3). Together these findings suggest that adiponectin regulated energy homeostasis through the AMPK/ACC pathway but not the JAK/STAT3 pathway in the hypothalamus.

High FFA-induced proliferation and apoptosis in human umbilical vein endothelial cell partly through Wnt/beta-catenin signal pathway.

Free fatty acids (FFA)-induced proliferation and apoptosis was studied in human umbilical vein endothelial cells (HUVECs). A recombinant adenovirus containing a RNAi cassette targeting the GSK-3beta gene was produced and its silencing effect on GSK-3beta gene was detected by Western blot analysis and immunohistochemistry assay in HUVECs. The effect of the RNAi on the protein level of beta-catenin was explored by transfecting the RNAi adenovirus to inhibit the expression of GSK-3beta protein. The subsequent effect on the Wnt/GSK-3beta/beta-catenin signal pathway and on proliferation and apoptosis of HUVECs cultured with FFAs, was analyzed by BrdU assay, Annexin V-FITC/PI Apoptosis Detection Kit, and 4',6-diamidino-2- phenylindole(DAPI) to explore the possible connection between the signaling pathway and FFA-induced proliferation and apoptosis. The Western blot results showed that the expression of GSK-3beta protein in HUVECs could be inhibited efficiently by the RNAi adenovirus, and that the protein level of beta-catenin was increased by RNAi adenovirus transfection. The results of the BrdU assay suggested that knockdown of GSK-3beta with the RNAi adenovirus may stimulate the proliferation of HUVECs. Apoptosis was observed in HUVECs exposed to FFAs (0.75 mmol/L) for 72 h, and this effect could be partly reversed when interfering with the RNAi adenovirus. It may be concluded that the RNAi adenovirus specific to GSK-3beta may partly protect HUVECs from apoptosis induced by FFAs, probably through the up-regulation of the Wnt/beta-catenin signal pathway.

Regulation of GSK-3 beta in the proliferation and apoptosis of human thyrocytes investigated using a GSK-3 beta-targeting RNAi adenovirus expression vector: involvement the Wnt/beta-catenin pathway.

Disorders in the proliferation and apoptosis of thyrocytes may induce goitre, adenoma and carcinoma in the thyroid. The Wnt/beta-catenin pathway has been demonstrated to be involved in the regulation of cell proliferation, differentiation and apoptosis in various cell lines. The regulatory mechanism on the proliferation and differentiation of thyrocytes is not well characterized. In the present study, a GSK-3beta-targeting RNA interference (RNAi) adenovirus vector was constructed and delivered to primary human thyrocytes. Results showed that the expression of beta-catenin protein in primary human thyrocytes was increased after GSK-3beta-targeting RNAi adenovirus infection, the proliferation of primary human thyrocytes was significantly stimulated using Bromodeoxyuridine (BrdU) assay, while cell apoptosis was slightly affected which was observed through flow cytometry. It is concluded that the Wnt/beta-catenin pathway plays a significant role in the regulation of the proliferation of primary human thyrocytes.

Clinical analysis of 249 cases of adrenal tumors in a Chinese hospital.

OBJECTIVE: This study was designed to evaluate the clinical and pathological characteristics of adrenal masses. METHODS: The clinical data of 249 cases of adrenal masses which were confirmed at operation and by pathology were analyzed. RESULTS: The series comprised 103 males and 146 females. Overall, females were more commonly represented than males, especially with Cushing's syndrome and typical pheochromocytoma (female:male ratio 3.3:1.9), however the prevalence of adrenal incidentalomas (AIs) in males and females was similar. In our series, 148 (59.4%) were symptomatic, of which 4 (2.7%) were malignant, and 101 (40.6%) were incidental, of which 20 (19.8%) were malignant. Hormonal work-up demonstrated that 30.3% of the AIs were functional. Of 109 adrenocortical adenomas, 47 were primary aldosteronism, 31 were Cushing's syndrome, 30 were AIs, and 1 was adrenal virilization. Of 72 benign pheochromocytomas, 51 were typical pheochromocytomas and 21 were AIs. Of 14 adrenal nodular hyperplasias, 6 were Cushing's syndrome and 8 were primary aldosteronism. Of the remaining 30 benign tumors, all presented as AIs. The diameter of malignant tumors (10.9 ± 5.6 cm) was significantly larger than that of benign tumors (4.5 ± 3.7 cm) (p < 0.001). CONCLUSION: This study shows a high rate of AIs in patients with adrenal masses selected for surgery. Hormone levels should be determined in symptomatic or incidental patients with adrenal masses. Imaging examination (CT and MRI) is the first method used to detect and localize adrenal masses. Tumor size is an important parameter of diagnosis and management of patients with adrenal masses, especially AIs.

Approach to parathyroid carcinoma (PC): seven cases and a review of the literature.

To summarize the experience in the diagnosis and treatment of seven cases with parathyroid carcinoma (PC). We collect seven parathyroid carcinoma cases of Fujian Provincial Hospital from January 2009 to December 2018. Reviewing and concluding the seven collected cases referring to relative reference domestic and abroad. All of the seven cases have hypercalcemia and a high level of parathyroid hormone (PTH) that were over two folds of the normal upper limit, even over 36 folds. The PC in seven cases were confirmed by routine histopathology and immunohistochemistry. All the cases went through surgery. Parathyroid carcinoma shows no specificity in clinical feature, it usually implicates in skeleton and urinary system. Routine serum calcium examination, serum PTH determination are helpful diagnosing PC before operation. The appropriate surgical procedure is parathyroidectomy combined with ipsilateral total thyroidectomy and neck dissection in levels of II, III, IV, V and VI.