[Retracted] Galectin­3 blockade suppresses the growth of cetuximab­resistant human oral squamous cell carcinoma.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Fig. 4C on p. 6 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had already been published. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 685, 2021; DOI: 10.3892/mmr.2021.12325].

Catalpol rescues cognitive deficits by attenuating amyloid ß plaques and neuroinflammation.

This study sought to investigate the anti-amyloid ß (Aß) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model. METHODS: The effects of catalpol on Aß formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability. APPswe/PS1ΔE9 mice were treated with catalpol, and their cognitive ability was investigated using the water maze and novel object recognition tests. Immunohistochemistry and immunofluorescence were used to probe for protein markers of microglia and astrocyte, Aß deposits, and NF-κB pathway activity. Aß peptides, neuroinflammation, and nitric oxide production were examined using ELISA and redox reactions. RESULTS: Catalpol potently inhibited Aß fibril and oligomer formation. In microglial cells stimulated by Aß, catalpol alleviated the expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and inducible nitric oxide synthase (iNOS) but promoted the expression of the anti-inflammatory cytokine IL-10. Catalpol alleviated the cytotoxic effects of Aß-exposed microglia on HT22 cells. Treatment with catalpol in APPswe/PS1ΔE9 mice downregulated neuroinflammation production, decreased Aß deposits in the brains and alleviated cognitive impairment. Catalpol treatment decreased the number of IBA-positive microglia and GFAP-positive astrocytes and their activities of the NF-κB pathway in the hippocampus of APPswe/PS1ΔE9 mice. CONCLUSION: The administration of catalpol protected neurons by preventing neuroinflammation and Aß deposits in an AD mouse model. Therefore, catalpol may be a promising strategy for treating AD.

Alterations in Amygdala/Hippocampal Volume Ratios in Children with Obstructive Sleep Apnea Syndrome Caused by Adenotonsillar Hypertrophy.

BACKGROUND Intermittent hypoxemia can cause changes in certain brain structures. However, in pediatric patients with obstructive sleep apnea (OSA) caused by adenotonsillar hypertrophy (ATH), there is only limited information on the effect of ATH-induced OSA on brain structures. This study sought to investigate alterations in amygdala and hippocampal volumes in children with OSA by ATH. MATERIAL AND METHODS Magnetic resonance imaging scans were applied in children who had ATH-induced OSA (ATH/OSA) and in healthy children. Amygdala and hippocampus volumes and adenoid sizes were measured on MRI volumetric images. The ratio of adenoid size/nasopharyngeal depth was used to describe the severity of adenoid hypertrophy. The clinical variables of the involved subjects were investigated. RESULTS One hundred ATH/OSA children and 100 healthy children without ATH/OSA participated in the study. The ATH/OSA children had higher amygdala volumes and amygdala/hippocampus volume ratios but lower hippocampus volumes than healthy controls, and the amygdala/hippocampus volume ratios were correlated with disease duration and hypoxemia conditions. However, our data showed that amygdala/hippocampus volume ratios were not correlated with the ratios of adenoid size/nasopharyngeal depth in the ATH/OSA children. In addition, the ratio of adenoid size/nasopharyngeal depths in ATH/OSA children was higher than that in healthy children in each subgroup based on the age of participants. CONCLUSIONS Compared to healthy controls, amygdala/hippocampus volume ratios are increased in children with ATH/OSA.

Galectin­3 blockade suppresses the growth of cetuximab­resistant human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a cancer associated with high mortality (accounting for 3.1/100,000 deaths per year in Brazil in 2013) and a high frequency of amplification in the expression of the epidermal growth factor receptor (EGFR). Treatment with the EGFR inhibitor cetuximab leads to drug resistance in patients with OSCC due to unknown mechanisms. Galectin­3 (Gal­3) is a ß­galactoside binding lectin that regulates multiple signaling pathways in cells. The present study aimed to investigate the effect of Gal­3 in cetuximab­resistant (cet­R) OSCC. The OSCC HSC3 cell line was selected to establish a mouse xenograft model, which was treated with cetuximab to induce resistance. Subsequently, a Gal­3 inhibitor was used to treat cet­R tumors, and the tumor volume was monitored. The expression of Gal­3, phosphorylated (p)­ERK1/2 and p­Akt was assessed using immunohistochemistry. The combined effect of cetuximab and the Gal­3 inhibitor on HSC3 tumor xenografts was also investigated. HSC3 cells were cultured in vitro to investigate the regulatory effects of Gal­3 on ERK1/2 and Akt via western blotting. In addition, the effects of the Gal­3 inhibitor on the proliferation, colony formation, invasion and apoptosis of HSC3 cells were investigated by performing Cell Counting Kit­8, colony formation, Transwell and apoptosis assays, respectively. In cet­R OSCC tumors, increased expression of Gal­3, p­ERK1/2 and p­Akt was observed. Further research demonstrated that Gal­3 regulated the expression of both ERK1/2 and Akt in HSC3 cells by promoting phosphorylation. Moreover, the Gal­3 inhibitor decreased the proliferation and invasion, but increased the apoptosis of cet­R HSC3 cells. In addition, the Gal­3 inhibitor suppressed the growth of cet­R tumors. Collectively, the results indicated that the Gal­3 inhibitor and cetuximab displayed a synergistic inhibitory effect on OSCC tumors. In summary, the present study demonstrated that Gal­3 may serve an important role in cet­R OSCC. The combination of cetuximab and the Gal­3 inhibitor may display a synergistic antitumor effect, thereby inhibiting the development of cetuximab resistance in OSCC.

SRPK2 Expression and Beta-Amyloid Accumulation Are Associated With BV2 Microglia Activation.

INTRODUCTION: The extracellular deposition of ß-amyloid (Aß) is a pathological hallmark in Alzheimer's disease (AD), which induces microglial activation in the pathology of AD. The expression of serine/threonine-protein kinase 2 (SRPK2) is increased in the brain tissues of patients with AD. In this study, we examined the effect of SRPK2 in the activation of microglia. METHODS: Microglia (BV2) cells were cultured and the expression of SRPK2 was enhanced by transfection of SRPK2 recombinant vectors or knockdown by SRPK2 small interfering RNA (siRNA). The cells were stimulated by lipopolysaccharide (LPS) + interferon-γ (IFN-γ) or Aß in vitro, generating inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-10, and IL-6], which were investigated by real-time quantitative PCR (qPCR) and ELISA. The proliferation ability of the BV2 cells with/without SRPK2 expression was evaluated by WST-1 under pressure in the presence of Aß. The effects of SRPK2 on microglia polarization were evaluated by investigating the expression of CD16/32 and CD206 by western blot and the expression of ionized calcium-binding adapter molecule-1 (IBA-1) and arginase-1 (Arg-1) by immunofluorescence. Hippocampal cells HT-22 were cultured with a BV2 cell (with/without SRPK2 expression)-derived medium stimulated by Aß or LPS + IFN-γ, prior to the evaluation of HT-22 cytotoxicity by assessment of cell viability. Possible relationships between Akt and SRPK2 in the BV2 cells were investigated by western blot. RESULTS: The expression of SRPK2 was related to the phenotype polarization changes of microglia with increased expression of CD16/32 and IBA-1. The expression of proinflammatory cytokines IL-6 and TNF-α was increased, whereas the expression of anti-inflammatory cytokine IL-10 was decreased in the BV2 cells with SRPK2 overexpression. Moreover, with the expression enhancement of SRPK2, the BV2 cells had a higher proliferation rate. Aß treatment can promote SRPK2 expression in BV2 cells. Aß or LPS + IFN-γ promoted the production of cytokines IL-6 and TNF-α but decreased cytokine IL-10 in the BV2 cells. SRPK2 deficiency alleviated the cytotoxic effects of Aß or LPS + IFN-γ exposed microglia on HT22 cells. In addition, the activated Akt pathway promoted the expression of SRPK2 in the BV2 cells. CONCLUSION: Our data have found that enhanced SRPK2 expression contributed to the proinflammatory activation of microglia. Thus, SRPK2 may be a key modulating pathway of inflammatory mediators in AD pathology.

Involvement of angiotensin II receptor type 1/NF-κB signaling in the development of endometriosis.

Endometriosis (EM) is a common disease in women; however, the signaling pathways and related genes underlying the mechanisms of EM remain unclear. The present study aimed to investigate the role of angiotensin II receptor type 1 (AGTR1) in the pathogenesis of EM. Human EM tissues were collected, and the expression levels of AGTR1 and NF-κB in the tissues were analyzed using immunochemistry and western blotting, while the estrogen levels in the EM tissues were determined by ELISA. In vitro human endometrial stromal cells were used to investigate the expression levels of AGTR1 following exposure to estrogen; the interaction between AGTR1 and NF-κB was determined using reverse transcription-quantitative PCR and western blotting; and the effects of AGTR1 on cell proliferation, as well as the apoptotic and migratory abilities of the cells were evaluated using WST-1 assays, wound healing assays and flow cytometry, respectively. It was observed that both the expression levels of AGTR1 and the activity of NF-κB were increased in human EM tissues and stromal cells, and this activation of AGTR1 subsequently increased the activity of NF-κB. Moreover, estrogen was found to regulate the expression levels of AGTR1 in stromal cells. The activation of AGTR1 was demonstrated to promote cell proliferation and migration, in addition to preventing cells from undergoing apoptosis. In conclusion, the present study suggested that the increased activity of the AGTR1-NF-κB axis following the decreased exposure to estrogen may be important for the pathogenesis of EM. In addition, AGTR1 may be a potential therapeutic target for the treatment of EM.

Maternal exposure to cold spells during pregnancy is associated with higher blood pressure and hypertension in offspring later in life.

We aimed to investigate whether month of birth is associated with blood pressure (BP) and prevalent hypertension in adults from a region with frost-free days of <150 days and average temperatures - 13°C in winter, Xinjiang, China. We analyzed data for 6158 subjects from several surveys. We divided participants into April to August (n = 2624) and September to March (n = 3534) groups, based on length of maternal exposure to cold months, and analyzed BP, prevalent hypertension, and related factors. Diastolic BP in total subjects and systolic and diastolic BP in male subjects born between April and August were significantly higher than in those born between September and March. In sensitivity analysis, untreated males born between April and August showed significantly higher systolic and diastolic BP than did their counterparts. Subjects born between April and August showed significantly higher prevalence of hypertension (31.3% vs 27.8%, P = .003), and isolated systolic (23.3% vs 20.8%, P = .018) and diastolic hypertension (24.5% vs 21.4%, P = .004), than those born between September and March, which is similar for men. Birth between April and August showed 1.68 (95% CI: 1.06-2.67, P = .027)-fold increased odds for the prevalence of hypertension, independent of gender, age, body mass index, waist circumference, cigarette consumption, alcohol intake, and family history, compared with their counterparts. In conclusion, maternal exposure to cold spells during pregnancy may be associated with the increased risk of hypertension in offspring later in life, particularly among males, suggesting the involvement of maternal cold exposure during pregnancy in offspring hypertension development.

Enhancement of FAK alleviates ventilator-induced alveolar epithelial cell injury.

Mechanical ventilation induces lung injury by damaging alveolar epithelial cells (AECs), but the pathogenesis remains unknown. Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that is involved in cell growth and intracellular signal transduction pathways. This study explored the potential role of FAK in AECs during lung injury induced by mechanical ventilation. High-volume mechanical ventilation (HMV) was used to create a mouse lung injury model, which was validated by analysis of lung weight, bronchoalveolar lavage fluid and histological investigation. The expression of FAK and Akt in AECs were evaluated. In addition, recombinant FAK was administered to mice via the tail vein, and then the extent of lung injury was assessed. Mouse AECs were cultured in vitro, and FAK expression in cells under stretch was investigated. The effects of FAK on cell proliferation, migration and apoptosis were investigated. The results showed that HMV decreased FAK expression in AECs of mice, while FAK supplementation attenuated lung injury, reduced protein levels/cell counts in the bronchoalveolar lavage fluid and decreased histological lung injury and oedema. The protective effect of FAK promoted AEC proliferation and migration and prevented cells from undergoing apoptosis, which restored the integrity of the alveoli through Akt pathway. Therefore, the decrease in FAK expression by HMV is essential for injury to epithelial cells and the disruption of alveolar integrity. FAK supplementation can reduce AEC injury associated with HMV.

Mild primary aldosteronism (PA) followed by overt PA are possibly the most common forms of low renin hypertension: a single-center retrospective study.

Low renin hypertension (LRH) is a common condition in hypertensive patients, and mainly includes primary aldosteronism (PA) and low renin essential hypertension. To investigate the distributions and clinical manifestations of the main LRH forms, we reviewed 1267 hypertensive patients who underwent assessment for plasma renin activity (PRA) and plasma aldosterone concentration (PAC) by standardized protocols in our specialized center. LRH was defined as PRA < 1.0 ng/mL/h. A saline infusion test (SIT) was performed when LRH patients showed positive screening results for PA. The main LRH forms were defined as follows: post-SIT PAC > 10 ng/dL as 'overt PA', post-SIT PAC 5-10 ng/dL as 'mild PA', and post-SIT PAC < 5 ng/dL or negative screening results as 'non-PA'. Overall, 760 patients were defined as LRH, with 160 classified as overt PA, 268 as mild PA, and 332 as non-PA. The total proportion of PA amounted to 56.3% with 21.0% overt PA and 35.3% mild PA. Compared with the mild PA, patients with overt PA had higher systolic and diastolic blood pressures, lower serum potassium, higher urine potassium excretion, more frequent incidence of stage 3 hypertension, hypokalemia, diabetes mellitus, and classical unilateral adenoma on computerized tomography (P < 0.05). PA including overt and mild forms is indeed a major form of LRH. Clinical manifestations in mild PA are less severe than those in overt PA. Nevertheless, mild PA is more prevalent than overt PA in LRH and should be recognized.

Prevalence, Awareness, Treatment, and Control and Related Factors of Hypertension in Multiethnic Agriculture, Stock-Raising, and Urban Xinjiang, Northwest China: A Cross-Sectional Screening for 47000 Adults.

BACKGROUND: Hypertension is the leading cause of cardiovascular disease. Distribution of hypertension and related factors among multiethnic population in Northwest China remains scarce. The aim was to determine prevalence, awareness, treatment, control, and risk factors associated with hypertension among multiethnic population in Northwest China. METHODS: We conducted a blood pressure (BP) screening project covering a third of adults in Emin Xinjiang, Northwest China, during 2014-2016. Hypertension was defined as systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, and/or taking antihypertension drugs. We compared prevalence, awareness, treatment, and control of hypertension and related factors by different regions (agriculture, stock-raising, or urban) and by ethnic groups. RESULTS: Totally 47,040 adults were screened with 48.5% women. Overall prevalence, awareness, treatment, and control of hypertension were 26.5%, 64.6%, 44.5%, and 15.3%, respectively. Age-gender-adjusted hypertension prevalence was higher in urban (28.2%) than in other regions and in Kazakh (30.3%) than in others. The lowest awareness and treatment rates were observed in the agricultural region and in Kazakh subjects, while the lowest control was in the stock-raising region (13.8%) and in Kazakh subjects (12.6%). After adjusting for age, gender, ethnicity, and regions, compared to normal weight, nonsmokers, and nondrinkers, obesity, smoking, and alcohol intake were significantly related to increased prevalence of hypertension by 94%, 1.5, and 3.9 folds, respectively. CONCLUSIONS: Disparities in hypertension control among regions and ethnic groups suggested inadequate screening and treatment, especially in stock-raising regions and Kazakh populations. Control of alcohol intake, smoking, and obesity should be at high priority of health promotion.

Serum lysosomal-associated membrane protein-2 levels are increased in small and medium-vessel vasculitis, especially in polyarteritis nodosa.

OBJECTIVES: Lysosomal-associated membrane protein-2 (LAMP-2) is a highly glycosylated type I glycoprotein ex- pressed on the membranes of neutrophils, endothelial cells and other cells, which are closely linked to subsets of systematic vasculitis. The aim of this study was to investigate whether serum LAMP-2 can be used as a biomarker in small and medium vessel vasculitis (SMVV). METHODS: Serum samples from 39 patients with SMVV (including ANCA-associated vasculitis (AAV) and polyarteritis nodosa (PAN)) confirmed by angiography and/or biopsy and 78 healthy controls (HC) were collected. Serum LAMP-2 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum LAMP-2 levels in SMVV patients were increased compared with HC (p<0.001). Serum LAMP-2 levels were significantly different between patients with active stage and those with inactive stage (p=0.024). Patients with renal involvement had higher LAMP-2 levels than patients with non-renal involvement at presentation (p=0.022). Furthermore, serum LAMP-2 levels were correlated with Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), hypersensitive CRP (Hs-CRP), serum creatinine (Scr) and 24-hour proteinuria (all p<0.05). Among SMVV subsets, serum LAMP-2 levels were signi cantly higher in PAN compared with AAV (p=0.003). In PAN patients, serum LAMP-2 levels were correlated with BVAS and Hs-CRP (all p<0.05). CONCLUSIONS: Serum LAMP-2 levels can reflect the disease activity and renal involvement of SMVV. Furthermore, serum LAMP-2 levels were significantly higher in PAN compared with AAV, and associated with disease activity. LAMP-2 might be a potential biomarker for SMVV, especially in PAN.

Trends in Lipids and Lipoproteins Among Adults in Northwestern Xinjiang, China, From 1998 Through 2015.

BACKGROUND: To examine trends in serum lipids in population in Northwestern Xinjiang between 1998 and 2015 and to provide clues for future prevention. METHODS: We enrolled 5,142 adults aged ≥30 years from seven independent cross-sectional studies conducted in 1998-2000, 2007-2008, and 2015. Blood lipid profiles, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured. RESULTS: The mean age was 48.5 years in 1998-2000, 47.9 years in 2007-2008, and 53.7 years in 2015. There was a declining trend in the prevalence of dyslipidemia among adults in northwestern Xinjiang. Mean LDL-C decreased during the same period, while mean HDL-C showed the opposite trend. Mean TC was 4.79 mmol/L in 1998-2000, 5.17 mmol/L in 2007-2008, and 4.59 mmol/L in 2015. The trend of mean TG was similar to that of TC. The prevalence of dyslipidemia was closely related with male gender, Mongolian ethnicity, hypertension, obesity, elevated fasting blood glucose, smoking, and drinking. CONCLUSION: Between 1998 and 2015, favorable trends in lipid levels have occurred among adults of Northwestern Xinjiang. However, further efforts are needed.

Colorectal cancer cell-derived exosomes containing miR-10b regulate fibroblast cells via the PI3K/Akt pathway.

BACKGROUND: Cancer-associated fibroblasts (CAFs) contribute to the proliferation of colorectal cancer(CRC) cells. However, the mechanism by which CAFs develop in the tumor microenvironment remains unknown. Exosomes may be involved in activating CAFs. METHODS: Using a miRNA expression profiling array, we determined the miRNA expression profile of secretory exosomes in CRC cells and then identified potential miRNAs with significant differential expression compared to normal cells via enrichment analysis. Predicted targets of candidate miRNAs were then assessed via bioinformatics analysis. Realtime qPCR, western blot, and cell cycle analyses were performed to evaluate the role of candidate exosomal miRNAs. Luciferase reporter assays were applied to confirm whether candidate exosomal miRNAs control target pathway expression. A CRC xenograft mouse model was constructed to evaluate tumor growth in vivo. RESULTS: Exosomes from CRC cells contained significantly higher levels of miR-10b than did exosomes from normal colorectal epithelial cells. Moreover, exosomes containing miR-10b were transferred to fibroblasts. Bioinformatics analysis identified PIK3CA, as a potential target of miR-10b. Luciferase reporter assays confirmed that miR-10b directly inhibited PIK3CA expression. Co-culturing fibroblasts with exosomes containing miR-10b significantly suppressed PIK3CA expression and decreased PI3K/Akt/mTOR pathway activity. Finally, exosomes containing miR-10b reduced fibroblast proliferation but promoted expression of TGF-ß and SM α-actin, suggesting that exosomal miR-10b may activate fibroblasts to become CAFs that express myofibroblast markers. These activated fibroblasts were able to promote CRC growth in vitro and in vivo. CONCLUSION: CRC-derived exosomes actively promote disease progression by modulating surrounding stromal cells, which subsequently acquire features of CAFs.

SIRT1 contributes to neuroendocrine differentiation of prostate cancer.

The epigenetic factor SIRT1 can promote prostate cancer progression, but it is unclear whether SIRT1 contributes to neuroendocrine differentiation. In this study, we showed that androgen deprivation can induce reactive oxygen species production and that reactive oxygen species, in turn, activate SIRT1 expression. The increased SIRT1 expression induces neuroendocrine differentiation of prostate cancer cells by activating the Akt pathway. In addition, the interaction between Akt and SIRT1 is independent of N-Myc and can drive the development of neuroendocrine prostate cancer when N-Myc is blocked. Furthermore, SIRT1 facilitates tumor maintenance, and targeting SIRT1 may reduce the tumor burden during androgen deprivation. Our findings suggest that SIRT1 is a potential target for therapeutic intervention.

Does increased serum d-lactate mean subclinical hyperpermeability of intestinal barrier in middle-aged nonobese males with OSA?

Few attention has been directed to the potential effects of intermittent hypoxia experienced in obstructive sleep apnea on the integrity and permeability of intestinal barrier, particularly in adults. Therefore, we evaluated alteration in serum d-lactate concentration in middle-aged males with obstructive sleep apnea to value permeability of intestinal barrier. In this current cross-sectional study, consecutive 159 males were studied. Obstructive sleep apnea was determined by polysomnography and apnea hypopnea index ≥15 event/h was defined as obstructive sleep apnea. D-lactate, lipopolysaccharide binding protein, interleukin-1ß, interleukin-6 and tumor necrosis factor-α by ELISA method. Nonobese obstructive sleep apnea (OSA) males showed significantly higher serum d-LA than did nonobese [1374.35 (816-1735) µg/L vs 1166.43 (730-1815) µg/L, P = .018], and obese non-OSA ones [1374.35 (816-1735) µg/L vs 1188.75 (736-1557) µg/L, P = .045], whereas serum LBP levels showed no differences within groups. Serum IL-1ß was also slightly higher in nonobese OSA males, but with statistical significance, than in nonobese (19.39 ±â€Š4.67 ng/L vs 17.25 ±â€Š3.66 ng/L, P = .041), and obese non-OSA ones (19.39 ±â€Š4.67 ng/L vs 17.42 ±â€Š3.79 ng/L, P = .047), whereas other biomarkers, IL-6 and TNF-a did not show significant differences among groups. In stepwise multiple linear regression analysis, serum d-LA was independently positively associated with AHI (B = 5.577, P = .022), and ODI3 (B = 4.550, P = .024) and negatively with LSaO2 (B = -12.234, P = .019). Finally, we arrived at a conclusion that serum d-lactate was increased in nonobese middle-aged males with obstrutive sleep apnea, possibly suggesting existence of subclinical disruption of intestinal barrier, and showed significant associations with inflammatory mediators, possibly being involved in systemic inflammation of obstructive sleep apnea.

Detection of Secondary Causes and Coexisting Diseases in Hypertensive Patients: OSA and PA Are the Common Causes Associated with Hypertension.

BACKGROUND: Since the control rate of blood pressure is lower in mainland China, the aim of this study is to investigate the proportion of secondary causes and coexisting diseases of hypertension in hypertensive patients. METHODS: Data on consecutive patients with hypertension who visited the Hypertension Center. Diseases were detected using an established strict screening protocol. RESULTS: Detection rate of secondary causes and coexisting diseases of hypertension was 39.5% among 3003 hypertensive patients. Obstructive sleep apnea (OSA) was the most common, accounting for 24.7% of patients, followed by primary aldosteronism (PA) (5.8%) and PA + OSA (4.9%). Endocrine hypertension accounted for 12.1% of patients, including 10.7% of patients with PA, 1.1% with hypothyroidism, 0.1% with pheochromocytoma, 0.1% with Cushing's syndrome, and 0.1% with hyperthyroidism, respectively. Those who smoke, those who are obese, and those who have diabetes accounted for 31.3%, 27.5%, and 16.6% of total patients, respectively. There were overlapping conditions in secondary causes and coexisting diseases of hypertension. OSA was the most common in each age- and BMI-stratified group. CONCLUSION: Findings from the current study suggest an increasing frequency of secondary forms of hypertension, highlighting the burden of OSA and PA in hypertensive patients.

Potential inflammatory markers in obstructive sleep apnea-hypopnea syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a complex chronic inflammatory respiratory disease with multiple pathogenic factors and high morbidity and mortality. Serum levels of nuclear factor-κB (NF-κB), hypoxia-inducible factor-1 alpha (HIF-1α), and surfactant protein D (SPD) were investigated in OSAHS patients, to determine their clinical significance and correlation with the pathogenesis. Patients were classified into a mild and moderate OSAHS group (n = 25) and severe OSAHS group (n = 33). Twenty healthy patients served as a control group. Peripheral blood levels of NF-κB, HIF-1α, and SPD were determined by Western blot, and a correlation analysis was performed. Severe OSAHS patients received nasal continuous positive airway pressure (nCPAP) therapy and were followed up after 2 months. NF-κB p65, HIF-1α, and SPD expression levels were determined after valid nCPAP therapy. NF-κB p65 and HIF-1α expression was significantly higher in severe OSAHS group than in the other two groups (p < 0.01), and was positively correlated with the apnea-hypopnea index (AHI) (r = 0.696, p < 0.001; r = 0.634, p < 0.001). SPD expression was significantly lower in severe OSAHS group than in the control group (p < 0.01) and mild and moderate OSAHS group (p < 0.01), and was negatively correlated with AHI (r = -0.569, p < 0.001). OSAHS pathogenesis was associated with changes in NF-κB, HIF-1α, and SPD protein expression levels. nCPAP therapy could improve the clinical characteristics of the patients, lower serum NF-κB and HIF-1α levels, and increase serum SPD levels. We conclude that OSAHS is related to the expression of NF-κB, HIF-1, and SPD.

Relationship between surfactant proteins B and C and obstructive sleep apnea: is serum SP-B concentration a potential biomarker of obstructive sleep apnea?

BACKGROUND: Surfactant proteins B and C are mainly synthesized, secreted by alveolar type II cells, and affected by hypoxia and mechanical stretches. We hypothesized that their serum levels might be altered by intermittent hypoxia and swing of intrathoracic pressure of obstructive sleep apnea (OSA). METHODS: Consecutive 140 middle-aged males, suspicious of OSA determined by polysomnography, were studied. Surfactant proteins B and C were determined by ELISA. RESULTS: Surfactant protein B (41.39 ± 6.01 vs 44.73 ± 7.62 ng/L, p = 0.005), not C (32.60 ± 6.00 vs 32.43 ± 6.44 ng/L, p = 0.61), significantly lowered in moderate to severe OSA subjects than in non to mild OSA subjects. Severity of OSA is inversely correlated with serum surfactant protein B. Adjusting age, body mass index, and smoking history, compared to subjects with surfactant protein B (SP-B) ≥43.35 ng/L, those with SP-B <43.35 ng/L showed significantly increased 1.528-fold risk for moderate to severe OSA (p = 0.009), whereas no association between surfactant protein C and OSA was observed. Prevalence of moderate to severe OSA in lower SP-B group is higher than that in higher SP-B group (62.7 vs 38.4 %, p = 0.003). Serial and parallel tests on Epworth sleep scale (ESS) and SP-B evaluation can be complementary and prove helpful with high specificity (94.44 %) and sensitivity (84.48 %) to detect moderate to severe OSA. CONCLUSIONS: Serum surfactant protein B, rather than C, is decreased in some individuals with moderate to severe OSA, compared to non to mild OSA subjects. Serum surfactant protein B might be a potential biomarker to diagnose OSA.

[An association study of six-transmembrane protein of prostate 2 gene with metabolic index and tumour necrosis factor in Uygur population].

OBJECTIVE: To explore the relationship between genetic polymorphisms of six-transmembrane protein of prostate 2 (STAMP2) and metabolic index, TNFα in Xinjiang Uygur population. METHODS: STAMP2 gene functional regions were sequenced in Uygur Xinjiang population diagnosed as metabolic syndrome. Patients were divided into the following three groups by their TNFα concentration: the high level group (TNFα ≥ 7.95 µg/L, n = 313), the moderate level group (TNFα >5.34- < 7.95 µg/L, n = 268) and the low level group ( ≤ 5.34 µg/L, n = 313) . The selected representative variations were genotyped by TaqMan-PCR in 894 Uygur individuals. The association of the genetic variations of STAMP2 gene with metabolic index and TNFα was analyzed. RESULTS: Three representative variations were genotyped, including rs8122, rs1981529 and rs34741656. The genotype distribution and allele frequencies of rs8122 and rs1981529 were statistically different among the three groups (P < 0.05), while no difference was observed with rs34741656 (P > 0.05). By ANOVA analysis, statistical difference was showed between the rs1981529 polymorphism AA and AG in the concentration of TNFα (P < 0.05) . None of the polymorphisms was significantly associated with TC, HDL-C, LDL-C and TG (P > 0.05). CONCLUSION: Two STAMP2 gene polymorphisms, rs8122 and rs1981529 are associated with the concentration of TNFα in Xinjiang Uygur population.

[Association of MK2 and ZFP36 gene polymorphisms with high density lipoprotein cholesterol in Uygur population from Hetian area of Xinjiang].

OBJECTIVE: To assess the association of genetic polymorphisms of mitogen-activated protein kinase activated protein kinase 2 gene (MK2) and zinc finger protein 36 gene (ZFP36) with high density lipoprotein cholesterol (HDL-C) in Xinjiang Urgur population. METHODS: Nine hundred thirty Uygur individuals were randomly recruited from Hetian area. Single nucleotide polymorphisms (SNP) in MK2 gene (rs44890 and rs45514798) and ZFP36 gene (rs251864 and rs3746083) were determined with Taqman-PCR. All subjects were investigated with questionnaire, physical examination and measurement of lipid levels and plasma tumor necrosis factor-alpha. RESULTS: (1)In Uygur men younger than 50 years old, SNP rs45514798 was associated with HDL-C [dominant model P=0.054, OR(95%CI)0.261(0.082-0.833) after age, smoking, drinking, abdominal circumference, waist/hip ratio and body mass index and tumor necrosis factor were controlled]. (2) For males younger than 50 years old, the concentration of total cholesterol, HDL-C, low density lipoprotein cholesterol were different in dominant model of rs45514798(P< 0.05). Female: total cholesterol, low density lipoprotein cholesterol were different in dominant model of rs45514798(P< 0.05). (3) The distribution of genotype of ZFP36 gene did not differ significantly between the low HDL-C groups and the control group. CONCLUSION: MK2 gene rs45514798 polymorphisms may be associated with HDL-C in Uygur men younger than 50 years old from Hetian area of Xinjiang. ZFP36 gene is not associated with HDL-C in Uygur people from Xinjiang.