Diagnostic performances of D-dimer, prothrombin time, and red blood cell distribution width for coronary artery lesion in children with acute stage Kawasaki disease.

Aim: To evaluate the performances of D-dimer, prothrombin time (PT), and red blood cell distribution width (RDW) for the diagnosis of coronary artery lesion (CAL) in acute stage Kawasaki disease (KD). Methods: Between January 2018 and January 2021, a total of 102 children with acute stage KD were included in this retrospective study. Among them, 36 KD children with CAL were divided into the CAL group, and 66 KD children without CAL were divided into the NCAL group. Independent predictors of CAL in acute stage KD were identified by using univariate and multivariate logistic regression analysis. Spearman correlations were used to evaluate the association between CAL in acute stage KD and different indicators. The diagnostic performance of different indicators for CAL in acute stage KD was analyzed by the receiver operating characteristic (ROC) curve. Results: Compared with the NCAL group, children in the CAL group had significantly higher white blood cell count, lymphocyte count, platelet count, D-dimer, and RDW levels, but lower PT levels (all p < 0.05). Logistic regression analysis revealed that D-dimer (OR = 1.0, 95% CI: 1.004-1.012, p < 0.001), PT (OR = 0.4, 95% CI: 0.2-0.8, p = 0.01), and RDW (OR = 7.0, 95% CI: 2.6-19.2, p < 0.001) were independent predictors of CAL in children with acute stage KD. CAL showed a positive correlation with D-dimer (r = 0.4, p < 0.001) and RDW (r = 0.5, p < 0.001), and had a negative association with PT (r = -0.2, p < 0.05). The ROC curve analysis showed that the combination of the three indicators had the highest diagnostic performance for CAL in acute stage KD with an area under the curve (AUC) of 0.922 (sensitivity, 86.1%; specificity, 89.4%), compared with D-dimer (AUC = 0.736), PT (AUC = 0.640), and RDW (AUC = 0.819) alone. Conclusion: A combination of D-dimer, PT, and RDW may help predict CAL in children with acute stage KD.

MicroRNA-188-5p inhibits hepatocellular carcinoma proliferation and migration by targeting forkhead box N2.

BACKGROUND: This study aimed to identify the biological functions, expression modes, and possible mechanisms underlying the relationship between metastatic human hepatocellular carcinoma (HCC) and MicroRNA-188-5p (miR-188) dysregulation using cell lines. METHODS: A decrease in miR-188 was detected in low and high metastatic HCC cells compared to that in normal hepatic cells and non-invasive cell lines. Gain- and loss-of-function experiments were performed in vitro to investigate the role of miR-188 in cancer cell (Hep3B, HepG2, HLF, and LM3) proliferation and migration. RESULTS: miR-188 mimic transfection inhibited the proliferation of metastatic HLF and LM3 cells but not non-invasive HepG2 and Hep3B cells; nonetheless, miR-188 suppression promoted the growth of HLF and LM3 cells. miR-188 upregulation inhibited the migratory rate and invasive capacity of HLF and LM3, rather than HepG2 and Hep3B cells, whereas transfection of a miR-188 inhibitor in HLF and LM3 cells had the opposite effects. Dual-luciferase reporter assays and bioinformatics prediction confirmed that miR-188 could directly target forkhead box N2 (FOXN2) in HLF and LM3 cells. Transfection of miR-188 mimics reduced FOXN2 levels, whereas miR-188 inhibition resulted in the opposite result, in HLF and LM3 cells. Overexpression of FOXN2 in HLF and LM3 cells abrogated miR-188 mimic-induced downregulation of proliferation, migration, and invasion. In addition, we found that miR-188 upregulation impaired tumor growth in vivo. CONCLUSIONS: In summary, this study showed thatmiR-188 inhibits the proliferation and migration of metastatic HCC cells by targeting FOXN2.

The Application of the Insulin to C-Peptide Molar Ratio (ICPR) in Primary Screening for Insulin Antibodies in Type 2 Diabetes Mellitus Patients: A Further Quantitative Study on the Relationship Between ICPR and Insulin Antibodies.

Purpose: This study aimed to further quantify the relationship between insulin antibodies (IAs) and the 2-hour insulin to C-peptide molar ratio (2h-ICPR) using a multiple linear regression model in T2DM patients. Methods: A total of 274 T2DM patients from April 2019 to December 2022 in Xiang'an Hospital of Xiamen University were included in this study. Multiple Linear Model Fitting was conducted on the candidate independent variables (age, BMI, HbA1c, and 2h-ICPR) for the multiple linear regression. The linear relationship between insulin antibodies (IAs) and the significant independent variables was presented by making multiple linear regression equations. Results: The total demographic characteristics of the included patients were as follows: age (51.92±13.10 years), BMI (24.94±3.99 kg/m2), HbA1c (9.70±2.39%), 2h-ICPR (0.12±0.11), and IAs (0.37±1.12COI). Linear relationships of independent variables: age (r=0.163, p=0.007), 2h-ICPR (r=0.259, p=0.001), BMI (r=0.007, p=0.907) and 2h-ICPR (r=0.092, p=0.129). Multiple linear regression: age (unstandardized ß=0.014, 95% CI: 0.004-0.024, p=0.004), 2h-ICPR (unstandardized ß=2.758, 95% CI: 1.555-3.962, p≤0.001). The regression equation: . Conclusion: The quantitative relationship between 2h-ICPR and insulin antibodies was . 2h-ICPR can be a preliminary screening indicator for insulin antibody testing in patients with type 2 diabetes.

Clinical diagnostic value of liquid chromatography-tandem mass spectrometry method for primary aldosteronism in patients with hypertension: A systematic review and meta-analysis.

Background: Primary aldosteronism (PA) is currently considered the most common cause of secondary and endocrine hypertension. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a new detection technique has been gradually applied in the diagnosis of PA. However, the diagnostic value of LC-MS/MS methods for PA has not been systematically clinically validated. The aim was to access the diagnostic accuracy, sensitivity, and specificity of LC-MS/MS methods as screening tools in PA. Materials and methods: A literature search of PubMed, Embase, Medline, Web of Science, Scopus, Science Direct, and Chinese databases was carried out to June 2022 with no language restriction. Data on sensitivity and specificity and other evaluation indicators were extracted and pooled with STATA and Meta-disc software. Heterogeneity was evaluated and meta-regression and subgroup analysis was performed to elucidate sources of heterogeneity. Results: 12 studies of the diagnostic test were suitable and included in the meta-analysis. Pooled sensitivity, specificity, and diagnostic odds ratio were 0.89 (95% CI: 0.83-0.93), 0.87 (95% CI: 0.82-0.91), and 55 (95% CI: 28-110), respectively. Subgroup analysis assessed the diagnostic power of LC-MS/MS based on the type of detection index. ARR and PAC based on LC-MS/MS methods have the higher diagnostic value compared with other indices, diagnostic odds ratios were 121.65 (95% CI: 36.28-407.98) and 49.85 (95% CI: 24.87-99.93). There was considerable heterogeneity among studies. Conclusion: LC-MS/MS methods had higher accuracy and reliability in the diagnosis of primary aldosteronism. LC-MS/MS-based ARR and PAC can be further promoted and applied in the diagnosis of primary aldosteronism.

Characteristics of OGTT and Correlation Between the Insulin to C-Peptide Molar Ratio, HOMA-IR, and Insulin Antibodies in T2DM Patients.

Purpose: The purpose of our study was to analyze the characteristics of OGTT and the correlation between the insulin to C-peptide molar ratio (ICPR), HOMA-IR and insulin antibodies (IAs) in T2DM patients. Patients and Methods: A total of 77 T2DM patients were included and divided into the IA+ group (25 patients) and IA- group (52 patients). The values of serum glucose, insulin, and C-peptide testing during 2-h OGTT were summarized comparatively, and ROC was made to analyze the predictive value of ICPR for IAs. Results: At each time point of OGTT, there was no significant difference in serum glucose and C-peptide changes (p>0.05). Serum insulin levels in positive patients were elevated or not at different time points of the OGTT but ICPR was significantly different (P<0.05) in the two groups. Spearman correlation coefficient analysis showed that the presence of insulin antibodies was correlated with ICPR, but not with HOMA-IR, and ICPR-2h had a better prediction capacity (AUC=0.735, the optimal cutoff-point=0.11, Se=0.760, Sp=0.635). Conclusion: T2DM patients with IAs showed no difference in serum glucose and serum C-peptide changes, but elevated or not insulin levels on the OGTTs, compared with negative patients. ICPR-2h can be a preliminary diagnostic index to timely predict IAs in T2DM patients.

Pilocarpine improves submandibular gland dysfunction in irradiated rats by downregulating the tight junction protein claudin-4.

OBJECTIVES: To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with pilocarpine. MATERIALS AND METHODS: In situ irradiation models of SMGs in Wistar rats were conducted, and the glands were exposed to X-radiation at a single dose of 20 Gy. Pilocarpine was intraperitoneally injected 60 min prior to radiation and continuous 6 days postirradiation for a total of 7 days. Salivary secretion, histological changes, pro-inflammatory cytokines, alterations in tight junctions (TJs), and functional membrane proteins aquaporin-5 (AQP5) and claudin-4 mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks after irradiation. RESULTS: Salivary secretion of the irradiated glands was reduced at 1 and 12 weeks. As well, acinar cell numbers, TJ width, and the levels of M3 receptor and AQP5 were decreased. In contrast, tumor necrosis factor-α, interleukin 6, interleukin 1α, and the expression of the TJ protein claudin-4 were significantly increased in irradiated SMGs. Notably, all the alterations were attenuated by pilocarpine treatment. CONCLUSIONS: Pilocarpine could improve the secretory function of irradiated rat SMGs via reducing inflammation, ameliorating the structural injury of TJs, and attenuating the up-regulation of claudin-4 expression.

[Damage on paracellular pathway and effect on tight junction protein claudin-4 in rat parotid glands caused by ionizing radiation].

PURPOSE: To investigate the effect and the potential mechanism of ionizing radiation on secretory function and tight junction (TJ) protein claudin-4 in paracellular pathway of rat parotid glands. METHODS: Twenty four 8-week-old male Wistar rats were randomly divided into one control group(n=6) and three irradiation groups (i.e., 1-week group post-irradiation, 4-week group post-irradiation, and 12-week group post-irradiation, 6 rats in each group). The experimental glands of irradiation groups were exposed to X-radiation in one-time single doses of 20 Gy. The residual salivary secretion of parotid glands was measured by Schirmer's test. The pathological changes of gland tissues were observed under light microscope after hematoxylin-eosin(H-E) staining. The changes of TJs ultrastructure were observed under transmission electron microscopy (TEM). Immunofluorescence staining and Western blot were used to detect the expression levels of muscarinic acetylcholine M3 subtype receptor, aquaporin 5 (AQP5), and claudin-4 proteins. The experimental results were analyzed with SPSS 23.0 software package for one-way analysis of variance. RESULTS: The residual salivarysecretion of irradiation group glands at 1, 4, and 12 weeks after irradiation was reduced compared with that of the control group(P<0.05), and the residual salivary secretion of irradiation group at 12 weeks was significantly lower than that at 4 weeks(P<0.05). Histologically, the dilation and congestion of interstitial vessels were observed at early stage after irradiation, and significant reduced number of acinar cells was found at late stage(P<0.05). In the irradiation groups, the ultrastructures of TJ were fuzzy, the electron density was decreased, and the TJ width at 1, 4, and 12 weeks was reduced compared with that in the control group. Immunofluorescence staining and Western blot indicated that the protein expression levels of M3 and AQP5 were down-regulated; however, the protein expression levels of claudin-4 were significantly increased at 1, 4, and 12 weeks after irradiation. CONCLUSIONS: After ionizing radiation, decreased secretory function of paracellular pathway, alterations in TJ structures, and up-regulation of claudin-4 expression may be involved in the mechanism of hyposecretion in rat parotid glands after irradiation.

Downregulation of lncRNA SBF2-AS1 inhibits hepatocellular carcinoma proliferation and migration by regulating the miR-361-5p/TGF-ß1 signaling pathway.

SBF2-AS1 is an oncogenic long non-coding RNA (lncRNA). However, its role and mechanism in hepatocellular carcinoma (HCC) is still not completely clear. The HepG2, Hep3B, Bel-7402 and HL-7702 cell lines were used in our experiments. The CCK-8 kit and EdU staining were applied to detect cell viability and multiplication. The wound healing and Boyden chamber cell migration assays were employed to test the migration ability of cells. The levels of TGF-ß1 mRNA, lncRNA SBF2-AS1, and miR-361-5p were assessed by real-time PCR. TGF-ß1 protein levels were evaluated by western blotting. The direct interaction between miR-361-5p and TGF-ß1 was determined by luciferase reporter assays. A xenograft mouse model (XMM) was established to comprehensively study the effect and mechanisms of lncRNA SBF2-AS1. lncRNA SBF2-AS1 concentration in HCC cells exceeded that in a normal hepatocyte cell line. The downregulation of lncRNA SBF2-AS1 upregulated miR-361-5p levels in HCC cells. And, miR-361-5p negatively regulate TGF-ß1 expression in HCC cells. The suppression of miR-361-5p attenuated the influence of lncRNA SBF2-AS1 downregulation on the viability, proliferation, and migration capability of HCC cells. Further, the downregulation of lncRNA SBF2-AS1 inhibited neoplasm growth in an XMM of HCC. Simultaneously, miR-361-5p was upregulated and TGF-ß1 was downregulated after lncRNA SBF2-AS1 knocked down. In conclusion, downregulation of lncRNA SBF2-AS1 inhibits HCC proliferation and migration through the regulation of the miR-361-5p/TGF-ß1 signaling pathway.

Effect of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands.

OBJECTIVES: This study aims to investigate the effects of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands (SMGs) and reveal the changes in the tight junction (TJ) protein claudin-4. METHODS: A total of 24 Wistar rats were randomly divided into control and irradiation groups. The irradiation groups were further divided into 1, 4, and 12 weeks groups after irradiation. One-time 20 Gy irradiation was given to the SMG area on the experimental side of the irradiation group. At 1, 4, and 12 weeks after irradiation, the secretion of SMGs was measured using the Schirmer's test. The pathological changes in the gland tissues were observed under light microscopy after hematoxylin⁃eosin (HE) staining. The changes in the TJ ultrastructure were observed under transmission electron microscopy. The immunofluorescence staining and Western blot were used to detect the expression levels of muscarinic acetylcholine M3 receptor, aquaporin 5 (AQP5), and claudin-4 protein. RESULTS: At 1, 4, and 12 weeks after irradiation, the secretion of SMGs in the irradiation group was significantly decreased and lower than that in the control group (P<0.01). At 1 week, the interstitial edema was observed in SMG tissues. Nuclear pyknosis, decreased number of acinar cells, and small focal necrosis with inflammatory infiltration were also observed over time. However, these changes were most evident at 12 weeks after irradiation. In the irradiation group, the TJ ultrastructure of glands at different times appeared to be fuzzy, collapsed, and had decreased electron density. Moreover, the width of TJs was remarkably decreased (P<0.01). The expression levels of M3 and AQP5 were decreased in a time-dependent manner, and the fluorescence intensity was significantly reduced after irradiation. However, the expression levels and fluorescence intensity of claudin-4 were enhanced in different degrees. CONCLUSIONS: The changes in the TJ structure, the upregulation of the claudin-4 expression, and the damage in the paracellular pathway were involved in the hyposecretion of SMGs after irradiation.

Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats.

To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20 Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12 weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

[Clinical evaluation of mandibular impacted third molar removed without surgical flaps].

PURPOSE: To evaluate the effect of impacted mandibular third molars extracted without surgical flaps. METHODS: Ninety-eight patients with impacted mandibular third molars were collected. A total of 112 teeth were divided into non-surgical flap group and surgical flap group. In non-surgical flap group, the teeth were removed by transection method or T-shaped truncation method, and triangular flaps were designed in the surgical flap group. Postoperative complications at 1 day, 3 days, and 1 week after operation were recorded, and statistical analysis was performed using SPSS 17.0 software package. RESULTS: Complications such as hemorrhage, swelling, pain, mouth opening limitation and impact on daily life at postoperative 1 day and 3 day in non-surgical flap group were significantly lower than in surgical flap group (P<0.05).There was no significant difference in average operation time between the two groups (P>0.05). CONCLUSIONS: Impacted mandibular third molar can be removed without surgical flaps in selected patients. It helps alleviate patients'postoperative complications and improve their quality of life.

[Meta-analysis of Zhibitai Capsules combined with statin in reducing blood lipid levels in patients with coronary heart disease].

To systematically review the efficacy and safety of Zhibitai Capsules combined with chemical drugs versus chemical drugs alone in regulating blood lipid of patients of coronary heart disease, so as to provide evidence-based reference for clinical treatment. In this study, PubMed, EMbase, Cochrane Library, China Knowledge Network Database(CNKI), Technology Journal Database(VIP) and WanFang Database(WanFang) were retrieved to find the randomized controlled trials(RCT) about therapeutic efficacy of Zhibitai Capsules combined with statins(experimental group)versus statins alone(control group)in the treatment of regulating blood lipid of patients with coronary heart disease. The retrieval time was restricted to be from the inception to October 2019. The data were extracted from the randomized controlled trials. Meta-analysis was conducted by RevMan 5.3 statistical software after quality evaluation by Cochrane 5.1.0 quality evaluation tool(blood lipid level, inflammation indicators, traditional Chinese medicine syndrome score and adverse reactions). A total of 11 RCT were included, involving 1 538 patients. The results of Meta-analysis showed that in terms of decrease of total cholesterol(MD=-0.15,95%CI[-0.25,-0.05],P=0.004), decrease of triglycerides improvement(MD=-0.16,95%CI[-0.23,-0.10],P<0.000 01), decrease of low-density lipoprotein(MD=-0.08,95%CI[-0.15,-0.01],P=0.03), and increase of high-density lipoprotein(MD=0.06,95%CI[0.03,0.10],P=0.000 2), experimental group was better than control group. At the same time, the incidence of adverse reactions were low in the experimental group(OR=0.40,95%CI[0.18,0.85],P=0.02). As a result, in treatment of coronary heart disease, the therapeutic efficacy of Zhibitai Capsules combined with statins is better than statins alone in lowering total cholesterol level, triglyceride level, low-density lipoprotein level, and increasing high-density lipoprotein level. Patients in the experimental group had a low incidence of adverse events, but the heterogeneity was slightly higher, and the result had a poor stability. However, due to the small sample size of studies included, some experimental designs were not perfect, which reduces the recommendation level and evidence intensity of this system evaluation. Therefore, high-quality multi-center, large-sample, randomized, double-blind randomized controlled trials are needed for providing more reliable basis.

Sleep duration and overweight in Chinese adolescents: a prospective longitudinal study with 2-year follow-up.

PURPOSE: This prospectively designed study aimed to investigate the association between sleep duration and overweight in a cohort of Chinese adolescents. METHODS: A school-based cohort study with a 2-year follow-up was conducted among Chinese adolescents in Ningbo region (China). For the baseline study, 1901 school-aged Chinese children aged 12-13 years were recruited. Finally, 1510 adolescents were successfully reinterviewed in October 2018. Participants were asked to complete a self-administered questionnaire, and their heights and weights were directly measured. RESULTS: Overweight adolescents had shorter sleep duration or later bedtimes than non-overweight children in baseline (P < 0.05). In the multivariable linear regression analysis, sleep duration was marginally significantly correlated with body mass index (BMI) at baseline and significantly correlated with this parameter at a 2-year follow-up (ß = - 0.23, 95% confidence interval (CI): - 0.51 to 0.04, P < 0.1; ß = - 0.27, 95% CI: - 0.42 to - 0.11, P < 0.05, respectively). After adjusting for potential confounders, the multivariable logistic regression analysis revealed associations of a longer sleep duration at baseline with a reduced likelihood of participants being overweight both at baseline and at follow-up (adjusted odds ratio (AOR) = 0.81, 95% CI: 0.66 to 1.00, P = 0.05; AOR = 0.43, 95% CI:0.24 to 0.76, P < 0.05, respectively). CONCLUSIONS: Shorter sleep was associated with an increased likelihood of being overweight in Chinese adolescents, while a 1-h decrease in sleep per night led to a more than 50% increase in the overweight risk at the 2-year follow-up.

Radiological appearance of hepatocellular carcinoma predicts the response to trans-arterial chemoembolization in patients undergoing liver transplantation.

BACKGROUND: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. METHODS: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. RESULTS: Eighty nine TACE procedures (1.35 ± 0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), "typical tumor enhancement" (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. CONCLUSIONS: The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

The ACE2 G8790A Polymorphism: Involvement in Type 2 Diabetes Mellitus Combined with Cerebral Stroke.

BACKGROUND: We aimed to investigate the correlations between ACE2 polymorphisms and type 2 diabetes mellitus (T2DM) combined with cerebral stroke (CS). METHODS: A total of 346 patients treated or hospitalized in our hospital were enrolled, including 181 cases without cerebrovascular complications (T2DM group) and 165 cases combined with CS (T2DM + CS group); 284 healthy individuals were selected as the control group. PCR-RFLP and ELISA were used to analyze ACE2 G8790A polymorphisms and serum ACE2 levels, respectively. RESULTS: Significant differences were observed in the genotype/allele frequency of ACE2 G8790A between the T2DM + CS and control groups, and the T2DM and T2DM + CS groups, and in the genotype frequency of ACE2 G8790A between the T2DM and the control groups. The A allele may increase the risk of T2DM combined with CS. The AA genotype may also increase the risk of T2DM combined with CS (OR = 3.733, 95%CI = 2.069-6.738; OR = 3.597, 95%CI = 1.884-6.867). Serum ACE2 levels showed statistically significant differences among the groups. Systolic pressure and diastolic pressure were protective factors of T2DM combined with CS. CONCLUSION: The ACE2 G8790A polymorphism in T2DM patients was correlated with CS, and the A allele might be a risk factor of T2DM combined with CS.

Splenectomy suppresses growth and metastasis of hepatocellular carcinoma through decreasing myeloid-derived suppressor cells in vivo.

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.

c-Jun N-terminal kinase inhibitor favors transforming growth factor-ß to antagonize hepatitis B virus X protein-induced cell growth promotion in hepatocellular carcinoma.

Transforming growth factor (TGF)-ß induces cell growth arrest in well-differentiated hepatocellular carcinoma (HCC) while hepatitis B virus X protein (HBx) minimizes the tumor suppression of TGF-ß signaling in early chronic hepatitis B. However, how to reverse the oncogenic effect of HBx and sustain the tumor-suppressive action of TGF-ß has yet to be investigated. The present study examined the effect of TGF-ß and a c-Jun N-terminal kinase (JNK) inhibitor on cell growth in HCC cells with forced expression of HBx. It was found that HBx promoted cell growth via activation of the JNK/pSMAD3L pathway and inhibition of the transforming growth factor-beta type I receptor (TßRI)/pSMAD3C pathway. pSMAD3L/SMAD4 and pSMAD3C/SMAD4 complexes antagonized each other to regulate c-Myc expression. In the absence of HBx, TGF-ß induced cell growth arrest through activation of the TßRI/pSMAD3C pathway in well-differentiated HCC cells. In the presence of HBx, TGF-ß had no effect on cell growth. JNK inhibitor SP600125 significantly reversed the oncogenic action of HBx and favored TGF-ß to regain the ability to inhibit the cell growth in HBx-expressing well-differentiated HCC cells. In conclusion, targeting JNK signaling favors TGF-ß to block HBx-induced cell growth promotion in well-differentiated HCC cells. As an adjunct to anti-viral therapy, the combination of TGF-ß and inhibition of JNK signaling is a potential therapy for HBV-infected HCC.

Lifestyle interventions for adults with impaired glucose tolerance: a systematic review and meta-analysis of the effects on glycemic control.

OBJECTIVE: Previous meta-analyses have demonstrated that lifestyle modification can reduce the blood glucose levels in patients with type 2 diabetes, although the effects of changes in the blood glucose level on impaired glucose tolerance (IGT) remain controversial. This review therefore aimed to determine the efficacy of lifestyle interventions in adults with IGT. METHODS: We searched the Medline, Cochrane Library, EMBASE and Science Citation Index databases and reference lists of the included articles. Two independent reviewers extracted the data and assessed the quality of the included studies; a total of nine randomized controlled trials met the inclusion criteria. In addition, we tested for trial heterogeneity and calculated the pooled effects size using the random effects model. RESULTS: The overall interventions were associated with a decline in the 2-hour plasma glucose levels [standardized mean differences (SMD) -0.56; 95% confidence interval (CI), -1.01 to -0.10; I(2), 96.6%]. Moreover, dietary intervention (SMD -0.53; 95% CI -0.77 to -0.28) and physical intervention (SMD -0.42; 95% CI -0.63 to -0.20) were each associated with a decline in the 2-hour plasma glucose levels compared with that observed in the control participants. The overall interventions were associated with a decline in the fasting plasma glucose (FPG) levels (SMD -0.27; 95% CI -0.38 to -0.15; I(2) = 47.1%). In addition, physical intervention (SMD -0.25; 95% CI -0.44 to -0.05) and combined dietary and physical intervention were each associated with a decreased FPG level (SMD -0.28; 95% CI -0.44 to -0.12) compared with that observed in the control participants. CONCLUSION: Lifestyle modification based on physical or dietary interventions or both is associated with improvements in the 2-hour plasma glucose and FPG levels in IGT patients.

MiR-132 prohibits proliferation, invasion, migration, and metastasis in breast cancer by targeting HN1.

Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cell lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3' UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.