Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) patients with depression have a higher risk of complications and mortality than T2DM without depression. However, the exact neuropathophysiological mechanism remains unclear. Consequently, the current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in T2DM patients with and without depression. METHODS: The demographic data, clinical variables, neuropsychological tests, and functional and anatomical magnetic resonance imaging of depressed T2DM (n = 47) of non-depressed T2DM (n = 59) and healthy controls (n = 41) were collected and evaluated. The correlation analysis, stepwise multiple linear regression, and receiver operating characteristic curve were performed for further analysis. RESULTS: Abnormal neural activities in the bilateral posterior cingulate cortex (PCC) and hippocampus were observed in depressed and non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore, the cortical amplitude of low-frequency fluctuation (ALFF) in PCC, subcortical DC in the putamen of depressed T2DM, and hippocampus of non-depressed T2DM was correlated with cognitive scores. In contrast, the cortical fractional ALFF in PCC of non-depressed T2DM was correlated with depression scores. CONCLUSIONS: The abnormalities of spontaneous cortical activity in PCC and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2DM. Notably, the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2DM, which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2DM. This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2DM with and without depression.

First-in-human evaluation of an independently developed Chinese robot-assisted system for percutaneous coronary intervention.

BACKGROUND: Several studies have proved the safety and feasibility of robot-assisted percutaneous coronary intervention (PCI) in reducing the occupational hazards of interventionists while achieving precision medicine. However, an independently developed robot-assisted system for PCI in China has not yet emerged. This study aimed to evaluate the safety and feasibility of a robot-assisted system for elective PCI in China. METHODS: This preclinical trial included 22 experimental pigs and preliminarily supported the safety and feasibility of the ETcath200 robot-assisted system for PCI. Then, eleven patients with coronary heart disease who met the inclusion criteria and had clinical indications for elective PCI were enrolled. PCI was performed using a robot-assisted system. The primary outcomes were clinical success (defined as visual estimated residual stenosis < 30% after PCI and no major adverse cardiovascular events during hospitalization and within 30 days after PCI) and technical success (defined as the ability to use the robot-assisted system to complete PCI successfully without conversion to the traditional manual PCI). RESULTS: Eleven patients were included in this clinical trial. A drug-eluting stent with a diameter of 3 mm (interquartile range: 2.75-3.5 mm) and a length of 26 mm (interquartile range: 22-28 mm) was deployed in all patients. The clinical success rate was 100%, with no PCI-related complications and no in-hospital or 30-day major adverse cardiovascular events, and the technical success rate was 100%. CONCLUSIONS: The results strongly suggest that the use of the independently developed robot-assisted system in China for elective PCI is feasible, safe, and effective.

Changes in tumor suppressors and inflammatory responses during hydrogen peroxide-induced senescence in rat fibroblasts.

Cell proliferation and senescence are processes induced by oxidative stress. In this study, we aimed to establish a cellular model of rapid proliferation and senescence of rat tail-tip fibroblasts by hydrogen peroxide (H2O2), a well-known oxidant. On this basis, changes in oxidative stress, inflammatory response and cell cycle of fibroblasts were studied. After H2O2 treatment, cell counting and flow cytometry results showed that 50 µM of H2O2 for 12 h and 100 µM for 8 h effectively promoted fibroblast proliferation, while 500 µM rapidly led to cell cycle arrest. In addition, stimulation with H2O2 at a concentration of 50 µM also promoted the inflammatory effects of the cells. At a concentration of 100 µM H2O2, the cellular antioxidant system began to collapse at 8 h and began to affect cellular activity. 500 µM of H2O2 at 4 h the levels of senescence-associated ß-galactosidase, a marker of senescence and oxidative stress, were almost positive in fibroblasts. In addition, we found that the risk of fibroblasts carcinogenesis increased with increased H2O2 stimulation. The results of this study indicate that H2O2 can cause rapid proliferation and senescence of fibroblasts and that its mechanism of action may be mainly through influencing cellular antioxidant systems, cellular inflammatory responses and cell cycle.

[Phospholipase Dα1 and hydrogen sulfide were involved in the allelopathy of oridonin to Arabidopsis thaliana]. / ç£·è„‚é ¶Dα1与H2Så‚ä¸Žå†¬å‡Œè‰ç”²ç´ å¯¹æ‹Ÿå—èŠ¥çš„åŒ–æ„Ÿä½œç”¨.

We investigated the signal relationship between phospholipase Dα1 (PLDα1) and the gas signal molecule hydrogen sulfide (H2S) in Arabidopsis thaliana response to the allelopathy of diterpenoid oridonin. The wild type Arabidopsis Columbia (WT), phospholipase Dα1 (PLDα1) deletion mutant pldα1, D-/L-cysteine desulfyrase synthetic deletion mutant d-cdes and l-cdes seedlings were used as experiment materials, while 60 µmol·L-1 oridonin was applied as treatment concentration. The results showed that oridonin significantly increased H2S content, PLD and D-/L-CDes activities, and gene expressions of PLDα1 and D-/L-CDes in WT. Under oridonin treatment, the D-CDes and L-CDes activities of pldɑ1 seedlings were significantly lower than those of WT. Both D-CDes and L-CDes activities increased after exogenous addition of phosphatidic acid (PA) and were higher than those of WT. Oridonin significantly inhibited root growth of four lines, with d-cdes and l-cdes being more sensitive to oridonin. Application of NaHS promoted root growth and endogenous H2S production of four lines under oridonin treatment, while application of PA increased root growth and endogenous H2S production in WT, pldɑ1 and l-cdes, but had no effect in d-cdes. These results indicated that PLDα1 and H2S played a vital role in driving the response of Arabidopsis to oridonin, and that PLDα1/PA was located at the upstream of D-CDes to participate the regulation of the H2S production and root growth.

[Current status of exclusive breastfeeding for the second child and factors influencing exclusive breastfeeding in the context of the universal two-child policy].

OBJECTIVE: To investigate the current status of exclusive breastfeeding for the second child in the context of the universal two-child policy and the factors influencing exclusive breastfeeding. METHODS: A self-designed questionnaire for the current status of breastfeeding and related factors influencing breastfeeding for the second child were used to survey 836 mothers with a second child, who were selected by cluster sampling, in Quzhou, Zhejiang, China. RESULTS: A total of 680 usable questionnaires were obtained. The rate of exclusive breastfeeding for the second child was significantly lower than for the first child (34.9% vs 42.2%; P<0.05). The univariate analysis revealed that there were significant differences between the exclusive and non-exclusive breastfeeding groups in the mother′s age, education background, occupation and time of maternity leave, mode of delivery of the first child, sex of the first child, feeding pattern of the first child, mode of delivery of the second child, whether the second child was admitted to the intensive care unit, whether the father supported breastfeeding, and whether the grandmother/maternal grandmother supported breastfeeding (P<0.05). The multivariate logistic regression analysis showed that artificial feeding+partial breastfeeding for the first child (OR=12.286, P<0.05), cesarean section for the second child (OR=1.724, P<0.05), and having no breastfeeding support from the maternal grandmother (OR=1.651, P<0.05) were main factors for influencing exclusive breastfeeding. CONCLUSIONS: The current status of exclusive breastfeeding for the second child is not optimistic in the context of the universal two-child policy. Education about breastfeeding should be taken seriously at the birth of the first child, the rate of cesarean section should be reduced, and the family members should support exclusive breastfeeding, in order to improve the status of exclusive breastfeeding.

Remote ischemic preconditioning reduces myocardial injury in patients undergoing coronary stent implantation.

BACKGROUND: Myocardial necrosis occurs frequently in elective percutaneous coronary intervention (PCI) and is associated with subsequent major adverse cardiovascular events (MACEs). This study assessed the protective effect of remote ischemic preconditioning (RIPC) in patients undergoing successful drug-eluting stent implantation with normal baseline troponin values. METHODS: We analyzed 205 participants with normal baseline troponin values undergoing successful coronary stent implantation. Subjects were randomized to 2 groups: The RIPC group (n = 101), whose members received RIPC (created by three 5-minute inflations of a pneumatic medical tourniquet cuff to 200 mm Hg around the upper arm, interspersed with 5-minute intervals of reperfusion) < 2 hours before the PCI procedure, and the control group (n = 104). RESULTS: The primary outcomes were high sensitive cardiac troponin I (hscTnI) levels and incidence of myocardial infarction (MI 4a, defined as hscTnI > 0.20 ng/mL) at 16 hours after the PCI procedure. The median hscTnI at 16 hours after PCI was lower in the RIPC group compared with the unpreconditioned, control group (0.11 vs 0.21 ng/mL; P < 0.01). The incidence of MI 4a was lower in the RIPC group compared with the control group (39% vs 54%, P < 0.05). Index of renal function showed no difference between the 2 groups at 16 hours after PCI (P > 0.05). CONCLUSION: RIPC reduced post-PCI TnI release and incidence of MI 4a in patients undergoing elective coronary stent implantation.

Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2.

Growing evidence indicates that some tumor suppressive miRNAs are subject to epigenetic modifications during carcinogenesis. Here, we found that a large miRNA cluster of C19MC was upregulated in HCC cells after combined treatment with DNA methylation inhibitor and histone deacetylase inhibitor. MiR-517a and miR-517c were strikingly different from the remaining 41 miRNAs in C19MC. Ectopic expression of MiR-517a and miR-517c inhibited cell proliferation by blocking G2/M transition, whereas down-regulation of miR-517a and miR-517c facilitated cell growth. We further showed Pyk2 is a target of miR-517a and miR-517c and both the miRNAs are downregulated in HCC samples. These data collectively suggest that down-regulation of both miR-517a and miR-517c contribute to HCC development through regulating Pyk2.

Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.

[The exploration of the academic thought of external treatment master-Wu ShiJi].

To explore Wu Shiji's academic thought, his external treatment method were arranged and summarized, such as treatment based on triple energizer differentiation, the theory of plaster heals various disease and the combination of the application of acupuncture, moxibustion and plaster etc. It has been proved that Wu's external treatment had compiled all the advantages of each school of Chinese medicine before his era, rich in content and convenient to use. So it values highly in clinical practice and has provided great convenience for the modern clinical research of external treatment.

DLK1 as a potential target against cancer stem/progenitor cells of hepatocellular carcinoma.

Delta-like 1 homolog (DLK1; Drosophila) is a hepatic stem/progenitor cell marker in fetal livers that plays a vital role in oncogenesis of hepatocellular carcinoma (HCC). The aim of this study is to investigate whether DLK1 could serve as a potential therapeutic target against cancer stem/progenitor cells of HCC. DLK1(+) and DLK1(-) cells were sorted by fluorescence-activated cell sorting and magnetic-activated cell sorting, respectively, and then were evaluated by flow cytometry. The biological behaviors of these isolated cells and those with DLK1 knockdown were assessed by growth curve, colony formation assay, spheroid colony formation, chemoresistance, and in vivo tumorigenicity. Adenovirus-mediated RNA interference was used to knockdown the endogenous DLK1. We found that DLK1(+) population was less than 10% in almost all 17 HCC cell lines examined. DLK1(+) HCC cells showed stronger ability of chemoresistance, colony formation, spheroid colony formation, and in vivo tumorigenicity compared with DLK1(-) cells. The DLK1(+) HCC cells could generate the progeny without DLK1 expression. Furthermore, DLK1 knockdown could suppress the ability of proliferation, colony formation, spheroid colony formation, and in vivo tumorigenicity of Hep3B and Huh-7 HCC cells. Our data suggested that DLK1(+) HCC cells have characteristics similar to those of cancer stem/progenitor cells. RNA interference against DLK1 can suppress the malignant behaviors of HCC cells, possibly through directly disrupting cancer stem/progenitor cells, which suggested that DLK1 could be a potential therapeutic target against the HCC stem/progenitor cells.

Is it necessary to stent renal artery stenosis patients before cardiopulmonary bypass procedures?

BACKGROUND: Acute kidney injury (AKI) is associated with poor prognosis after cardiopulmonary bypass. The aim of this retrospective study was to investigate whether stent implantation before cardiopulmonary bypass has beneficial effect on development of AKI in renal artery stenosis (RAS) patients. METHODS: In this retrospective study, patients with abnormal baseline serum creatinine (SCr, > 106 µmol/L) were not included. Included patients (n = 69) were divided into two groups. Group 1 included 31 RAS patients receiving no stent implantation before cardiopulmonary bypass. Group 2 included 38 RAS patients having received stent implantation just before cardiopulmonary bypass. To assess AKI after cardiopulmonary bypass, serum urea nitrogen, SCr and creatinine clearance were recorded at baseline, at the end of operation, during the first and second postoperative 24 hours. RESULTS: Baseline characteristics were similar between groups. Serum urea nitrogen, SCr, creatinine clearance before and after cardiopulmonary bypass were also similar class groups. Incidence of AKI in group 1 was not significantly different from group 2. In group 1, AKI defined by RIFLE between occurred in 7 (22.6%) patients: 5 (16.1%) with RIFLE-R, 2 (6.5%) with RIFLE-I, and no patients with RIFLE-F. In group 2, 10 patients (26.3%) had an episode of AKI during hospitalization: 6 (15.8%) had RIFLE-R, 4 (10.5%) had RIFLE-I, and no patients had RIFLE-F. CONCLUSIONS: There are no data suggesting that it is necessary to stent RAS patients with normal SCr before cardio-pulmonary bypass. However, it cannot be concluded that RAS is not associated with AKI after cardiopulmonary bypass.

Expression of a novel gene FAM43B repressing cell proliferation is regulated by DNA methylation in hepatocellular carcinoma cell lines.

The epigenetic dysregulation of tumor suppressor genes plays an important role in many cancers, including hepatocellular carcinoma (HCC). In this study, we identified a new gene, family with sequence similarity 43, member B (FAM43B), based on a previous genome-wide approach. FAM43B was significantly downregulated in 60% (24/40) HCC specimens as compared to non-HCC livers. Enforced FAM43B overexpression could suppress cell growth and colony formation in vitro, and induce cell cycle delay, whereas FAM43B knockdown enhanced cell growth. The expression level of FAM43B was found related to the methylation level of FAM43B promoter in HCC cell lines and HCC specimens. The collective data suggest that the expression of FAM43B was regulated by methylation and the epigenetic silencing of FAM43B could contribute to HCC tumorigenesis by regulating cell proliferation.