The Intestinal Microbiota Composition in Early and Late Stages of Diabetic Kidney Disease.

Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved in the development of diabetic kidney diseases (DKD). The objective of this study was to determine bacterial taxa biomarkers during the progression of DKD by investigating bacterial compositional changes in early and late DKD. 16S rRNA gene sequencing was performed on fecal samples, including the diabetes mellitus (DM), DNa (early DKD), and DNb (late DKD) groups. Taxonomic annotation of microbial composition was performed. Samples were sequenced on the Illumina NovaSeq platform. At the genus level, we found counts of Fusobacterium, Parabacteroides, and Ruminococcus_gnavus were significantly elevated both in the DNa group (P = 0.0001, 0.0007, and 0.0174, respectively) and the DNb group (P < 0.0001, 0.0012, and 0.0003, respectively) compared with those in the DM group. Only the level of Agathobacter was significantly decreased in the DNa group than the DM group and in the DNb group than the DNa group. Counts of Prevotella_9, Roseburia were significantly decreased in the DNa group compared with those in the DM group (P = 0.001 and 0.006, respectively) and in the DNb group compared with those in the DM group (P < 0.0001 and 0.003, respectively). Levels of Agathobacter, Prevotella_9, Lachnospira, and Roseburia were positively correlated with an estimated glomerular filtration rate (eGFR), but negatively correlated with microalbuminuria (MAU), 24 h urinary protein quantity (24hUP), and serum creatinine (Scr). Moreover, the areas under the curve (AUCs) of Agathobacter and Fusobacteria were 83.33% and 80.77%, respectively, for the DM and DNa cohorts, respectively. Notably, the largest AUC for DNa and DNb cohorts was also that of Agathobacter at 83.60%. Gut microbiota dysbiosis was found in the early and late stages of DKD, especially in the early stage. Agathobacter may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD. IMPORTANCE It is not clear as to whether gut microbiota dysbiosis is involved in the progression of DKD. This study may be the first to explore gut microbiota compositional changes in diabetes, early-DKD, and late DKD. We identify different gut microbial characteristics during different stages of DKD. Gut microbiota dysbiosis is found in the early and late stages of DKD. Agathobacter may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD, although further studies are warranted to illustrate these mechanisms.

Solitary splenic tuberculosis: A case report.

BACKGROUND: Solitary splenic tuberculosis (TB) is unusual and rarely reported. Whether splenic TB is best treated surgically is still controversial. We describe a 73-year-old man with solitary splenic TB and no extrapulmonary TB. CASE SUMMARY: We report the case of a 73-year-old man with solitary splenic TB who complained of emaciation and fatigue. Abdominal computed tomography (CT) images suggested a splenic space-occupying lesion. We then performed a CT-guided splenic biopsy. The postoperative pathological examination revealed splenic TB. The patient took quadruple anti-TB medication. After 1 year, the patient recovered his normal weight and had no feeling of fatigue, and the splenic lesion had shrunk significantly. CONCLUSION: If patients receive combined, appropriate, regular, full-time anti-TB treatment, solitary splenic TB may be cured.

Retraction Notice to: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.06.005.].

Identification, diagnosis, and early intervention of children with developmental language disorder in Ningxia.

Background: It is reported that the incidence of language development disorder in children at the age of 2 is as high as 17.0%. Timely discovery of the high-risk factors of language development disorder in children and early intervention can greatly reduce the incidence of language development disorder and shorten the course and condition of the patients with language development disorder. Therefore, in order to facilitate prompt diagnosis and early interventions for children with language development disorder (DLD) and improve their language ability, this study explored the influence of perinatal factors on the language development of children in Ningxia and identified the unfavorable and favorable factors that influenced language development. Methods: Children diagnosed in the General Hospital of Ningxia Medical University during 2018-2021 who met the screening criteria for DLD and practical pediatric diagnostic criteria for DLD were enrolled in this study. Perinatal factors (gestational age, weight, sex, delivery mode, maternal age, presence of intrauterine infection, asphyxia) were retrospectively analyzed. The perinatal factors affecting language development were assessed using a one-way analysis of variance (ANOVA). Results: Among 1,500 children aged 0-3, 240 cases (16.00%) had language delay. Of these, 122 were male and 118 were female. There were 115 cases of comprehension and expression disorder, 30 cases of articulation disorder, and 90 cases of mixed manifestation. And there were 194 cases with definite intrauterine and perinatal high-risk factors or neonatal diseases, accounting for 80.83% of the total number of children with language delay. Conclusions: In Ningxia, factors in the neonatal period are the main cause of DLD, followed by fetal and maternal factors. Ischemic encephalopathy is the most common factor.

The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetic nephropathy is a common and serious complication of diabetes mellitus (DM) and is one of the leading causes of end-stage renal disease worldwide. Although there have been many investigations on biomarkers for DN, there is no consistent conclusion about reliable biomarkers. The purpose of this study was to perform a systematic review and meta-analysis of the role of circulating retinol-binding protein 4 (RBP4) in the type 2 diabetes mellitus (T2DM) patients with kidney diseases. MATERIALS AND METHODS: We searched the PubMed, MEDLINE, EMBASE, and Web of Science databases for publications. For the 12 cross-sectional studies that we included in the review, we calculated standard mean differences (SMD) with 95% confidence intervals (CI) for continuous data when the applied scales were different. Risk of bias of included trials was assessed by using the Newcastle-Ottawa Scale. RESULTS: RBP4 concentrations in the micro-, macro-, or micro+macroalbuminuria groups were significantly higher than those in the normal albuminuria group of T2DM patients [P = 0.001, SMD 1.07, 95% CI (0.41, 1.73)]. The estimated glomerular filtration rate (eGFR) was negatively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher's Z = -0.48, 95% CI (-0.69, -0.26), P < 0.0001]. The albumin-to-creatinine ratio (ACR) was positively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher's Z = 0.20, 95% CI (0.08, 0.32), P = 0.001]. CONCLUSION: The levels of circulating RBP4 were significantly higher both in T2DM subjects with micro/macroalbuminuria and in T2DM subjects with declined eGFR. The levels of circulating RBP4 were positively correlated with ACR but negatively correlated with eGFR. Circulating RBP4 could be a reliable biomarker for kidney diseases in T2DM.

Prevalence of multiple anxiety disorder and associated factors among adolescents three years after Ya’an Earthqhake / 中国学校卫生

Objective@#To examine the prevalence of multiple anxiety disorder of adolescents in Lushan, Sichuan and to provide the scientific reference for a long-term psychological intervention and rehabilitation for adolescents after earthquake.@*Methods@#In May 2016, 3 741 students were sampled in two middle schools and two high schools in Lushan county. Self-report questionnaice regarding exposure to earthquake, Screen for Child Anxiety Related Emotional Disorders (SCARED), and negative life events questionnaire (ASLES) were administered to the subjects.@*Results@#The prevalence of anxiety symptoms of adolescents in Lushan, Sichuan was 42.3%, among which panic disorder was 36.3%; generalized anxiety was 29.5%, separation anxiety was 40.3%, social anxiety was 26.1%, school fear was 32.4%. Junior school students resported more symptoms of separation anxiety than high school students (χ2=33.09, P<0.01). The results of Logistic regression showed that girls (OR=2.34, 95%CI=2.00-2.74, P<0.01), high negative life events (OR=2.87, 95%CI=2.60-3.17, P<0.01), trapped in earthqnakes (OR=1.77, 95%CI=1.18-2.67, P<0.01), parents injured (OR=1.22, 95%CI=1.03-1.43, P=0.02), experienced extreme fear (OR=1.78, 95%CI=1.52-2.08, P<0.01) were associated with higher risk of anxiety disorder.@*Conclusion@#High prevalence of anxiety disorder among adolescent following disaster need to be alerted. Adolescents among female victim or those experienced extreme fear emotion or high frequencies of negative life events, need specific intervention.

ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway.

Intracranial aneurysm (IA) rupture is a major cause of stroke death. Alteration of vascular smooth muscle cell (VSMC) function and phenotypic modulation plays a role in aneurysm progression. In the present study, we investigated the role of Annexin A3 (ANXA3) silencing in IA with the interaction of the c-Jun N-terminal kinase (JNK) signaling pathway. In IA and VSMCs of IA, the relationship between ANXA3 and the JNK signaling pathway was verified. To investigate the specific mechanism of ANXA3 silencing in IA, we transfected VSMCs with the overexpressed or small interfering RNA (siRNA) of ANXA3, or treated them with an inhibitor of the JNK signaling (SP600125). Cell counting kit-8 (CCK-8) assay was conducted to detect cell viability, and flow cytometry was conducted to assess cell cycle and apoptosis so as to evaluate the gain- and loss-of-function of ANXA3 and investigate the involvement of the JNK signaling pathway. The aneurysm wall of IA cells demonstrated an elevated level of ANXA3 expression and an activated JNK signaling pathway. VSMCs treated with siRNA-ANXA3 or SP600125 showed decreased expression of JNK, caspase-3, osteopontin (OPN), Bax, and matrix metalloproteinase-9 (MMP-9), as well as phosphate (p)-JNK, but increased the expression of α smooth muscle actin (α-SMA), ß-tubulin, and Bcl-2. ANXA3 silencing or inactivation of the JNK signaling pathway also enhanced proliferation and repressed apoptosis of VSMCs. Collectively, this study shows that the silencing of ANXA3 can rescue VSMC function in IAs by inhibiting the phosphorylation and activation of the JNK signaling pathway. These findings may provide a potential therapy for the molecular treatment of IAs.

MicroRNA-143-5p targeting eEF2 gene mediates intervertebral disc degeneration through the AMPK signaling pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major contributor to back, neck, and radicular pain, and the treatment of IDD is costly and relatively ineffective. Dysregulation of microRNAs (miRNAs) has been reported to be involved in IDD. The purpose of our study is to illustrate the potential that miR-143-5p targeting eEF2 gene mediates IDD. METHODS: Following the establishment of the IDD rat models, expression of miR-143-5p, eEF2, Bcl-2, Bax, AMPK, mTOR, cyclinD, COL2, ACAN, and DCN was detected. The NP cells isolated from degenerative intervertebral disc (IVD) were introduced with a series of mimic, inhibitor, or AICAR to explore the functional role of miR-143-5p in IDD and to characterize the relationship between miR-143-5p and eEF2. Cell viability, cell cycle, apoptosis, and senescence were also evaluated. RESULTS: A reduction in eEF2, an increase in miR-143-5p, and activation of the AMPK signaling pathway were observed in degenerative IVD. Moreover, increased senescent NP cells were observed in degenerative IVD. eEF2 was confirmed as a target gene of miR-143-5p. miR-143-5p was found to activate the AMPK signaling pathway. The restoration of miR-143-5p or the activation of AMPK signaling pathway decreased COL2, ACAN, and DCN expression, coupled with the inhibition of NP cell proliferation and differentiation, and promotion of NP apoptosis and senescence. On the contrary, the inhibition of miR-143-5p led to the reversed results. CONCLUSION: The results demonstrated that the inhibition of miR-143-5p may act as a suppressor for the progression of IDD.

Roles of 12-Lipoxygenase and Its Interaction with Angiotensin II on p21 and p27 Expression in Diabetic Nephropathy.

BACKGROUND: 12-Lipoxygenase (12-LO) and angiotensin II (Ang II) are involved in the development of diabetic renal hypertrophy, in which cyclin-kinase inhibitors, p21 and p27 play pivotal roles. Here, we study the effects of 12-LO and its interaction with Ang II on glomerular p21 and p27 expression in diabetic conditions. METHODS: Models used in the current study include glomerular mesangial cells (MCs); and glomeruli from (1) type 2 diabetic db/db mice; (2) type 2 diabetic rats induced by high-fat diet feeding followed by streptozotocin injection; (3) 12-LO knockout (12-LOKO) mice; and (4) normal rats infused with Ang II or 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE, arachidonic acid metabolite of 12-LO). RESULTS: The protein expression levels of p21 and p27 were increased in high glucose-stimulated MCs and in glomeruli isolated from db/db mice. In type 2 diabetic rats, cinnamyl-3,4-dihydroxy-α-cynanocinnamate (inhibitor of 12-LO) attenuated the increases in glomerular p21 and p27 protein expression, while in normal rats, 12(S)-HETE injection increased glomerular p21 and p27 expression. 12(S)-HETE and Ang II were mutually stimulated in glomeruli. Glomerular p21 and p27 expression were decreased in 12-LOKO mice compared to levels in control mice, and Ang II stimulation increased the protein expression of p27 in control but not 12-LOKO mice. Ang II stimulation had no effect on p21 protein expression in 12-LOKO mice. CONCLUSION: 12-LO is involved in diabetic renal hypertrophy via the induction of p21 and p27 protein expression and interacts with Ang II to induce p27 upregulation in diabetes. The current results suggest a potential amplifying loop in the pathogenesis of diabetic nephropathy.

Effect of oral polyethylene glycol at different time for painless colonoscopy preparation / 中国内镜杂志

Objective To compare the efficacy and comfort of oral polyethylene glycol at different time for painless colonoscopy preparation. Methods According to time of oral compound polyethylene glycol electrolyte powder, 173 painless colonoscopy patients were divided into group A, group B and group C. Patients in group A took 4 boxes of compound polyethylene glycol electrolyte powder for colonic preparation at 22:00 on day 1 before the check, the time of painless colonoscopy is 8:30 ~ 10:30. Group B patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 5:00 am on check day, the time of painless colonoscopy is 10:30 ~ 12:30. Group C patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 7:00 am on check day, the time of painless colonoscopy is 13:30 ~ 15:30. At last, we compare the colon cleanliness and comfort of patients among the three groups. Results There was no significant difference in instetinal cleanliness among the 3 groups (P > 0.05), but there was greatly significant difference in subjective tolerance among 3 groups (P < 0.05). Conclusion The 3 methods of having boxes of compound polyethylene glycol electrolyte power all have the satisfying effect for colonic preparation, but fractionated dose polyethylene glycol electrolyte power provides a better tolerance for bowel preparation of painless colonscopy.

Effect of oral polyethylene glycol at different time for painless colonoscopy preparation / 中国内镜杂志

Objective To compare the efficacy and comfort of oral polyethylene glycol at different time for painless colonoscopy preparation. Methods According to time of oral compound polyethylene glycol electrolyte powder, 173 painless colonoscopy patients were divided into group A, group B and group C. Patients in group A took 4 boxes of compound polyethylene glycol electrolyte powder for colonic preparation at 22:00 on day 1 before the check, the time of painless colonoscopy is 8:30 ~ 10:30. Group B patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 5:00 am on check day, the time of painless colonoscopy is 10:30 ~ 12:30. Group C patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 7:00 am on check day, the time of painless colonoscopy is 13:30 ~ 15:30. At last, we compare the colon cleanliness and comfort of patients among the three groups. Results There was no significant difference in instetinal cleanliness among the 3 groups (P > 0.05), but there was greatly significant difference in subjective tolerance among 3 groups (P < 0.05). Conclusion The 3 methods of having boxes of compound polyethylene glycol electrolyte power all have the satisfying effect for colonic preparation, but fractionated dose polyethylene glycol electrolyte power provides a better tolerance for bowel preparation of painless colonscopy.

12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance.

(1) BACKGROUND: 12-lipoxygenase (12-LO) is involved in the development of diabetic nephropathy (DN). In the present study, we investigated whether 12-LO inhibition may ameliorate type-2 DN (T2DN) by interfering with insulin resistance (IR); (2) METHODS: Rat glomerular mesangial cells, glomeruli and skeletal muscles were isolated and used in this study. Kidney histological changes were confirmed by periodic-acid Schiff staining; mRNA expression was detected by competitive reverse transcription polymerase chain reaction; and the protein level was determined by Western blot and the enzyme-linked immunosorbent assay, respectively; (3) RESULTS: The inhibition of 12-LO attenuated microalbuminuria (MAU) increases in type-2 diabetic rats, but not in type-1 diabetic rats. Infusion of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly increased the expression of angiotensin II (Ang II) and Ang II type 1 receptor (AT1R), but decreased the expression of AT1R-associated protein (ATRAP) in rat glomeruli, compared to the control. An in vitro study revealed that both 12(S)-HETE and insulin upregulated AT1R expression in rat mesangial cells. In the presence of p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190, the 12(S)-HETE-induced ATRAP reduction was significantly abolished. Interestingly, 12-LO inhibition did not influence AT1R expression in type-1 diabetic rats, but significantly abolished the increased AT1R and Ang II expression in glomeruli of type-2 diabetic rats. Furthermore, the inhibition of 12-LO significantly corrected impaired insulin sensitivity and fast serum insulin level, as well as the p-AMP-activated protein kinase (AMPK) reduction in skeletal muscle of type-2 diabetic rats; (4) CONCLUSION: The inhibition of 12-LO potentially ameliorated MAU by preventing IR through the downregulation of glomerular AT1R expression in T2DN.

Effect of angiotensin II type 1 receptor blocker on 12-lipoxygenase activity and slit diaphragm protein expression in type 2 diabetic rat glomeruli.

BACKGROUND: The 12-lipoxygenase (12-LO) and angiotensin II (Ang II) interaction plays an important role in diabetic nephropathy (DN). Proteinuria in DN is associated with decreased slit diaphragm proteins including nephrin and P-cadherin. Therefore, we investigated whether Ang II type 1 receptor (AT1) blocker (ARB) regulates 12-LO activity and slit diaphragm protein expression in diabetic rat glomeruli. METHOD: Glomeruli were isolated with the sieving method, and classified into small glomeruli (SG; 75-µm sieve) and large glomeruli (LG; 125-µm sieve). RESULTS: 12(S)-HETE, a lipid product of 12-LO, was increased by Ang II in the glomeruli. Infusion of 12(S)-HETE and Ang II significantly decreased nephrin expression in LG, but increased it in SG compared to control. Glomerular P-cadherin expression was reduced after Ang II and 12(S)-HETE treatment without differences between LG and SG. ARB did not influence glycemic levels but completely abolished the increases in 12(S)-HETE, AT1 expression, and proteinuria in diabetic rats. Nephrin expression was significantly reduced in LG but increased in SG in diabetic rats compared to control. P-cadherin expression decreased in both diabetic LG and SG. The abnormalities of nephrin and P-cadherin were partially but significantly reversed by ARB. CONCLUSION: ARB potentially ameliorates DN via the up-regulation of glomerular nephrin and P-cadherin expression through the inhibition of 12-LO activation in the glomeruli of rats with DN.

Incidence and clinical characteristics of transient ST-T elevation during transseptal catheterization for atrial fibrillation ablation.

AIMS: Transient ST-T elevation (STE) is a rare complication that occurs during transseptal catheterization. This study aims to delineate the incidence and characteristics of transient STE during transseptal catheterization for atrial fibrillation (AF) ablation. METHODS AND RESULTS: Consecutive patients who underwent fluoroscopy-guided transseptal catheterization for circumferential pulmonary vein radiofrequency ablation in Beijing An Zhen Hospital from January 2006 to January 2013 were enrolled in this study. Out of 2965 patients with a total of 3452 transseptal catheterization procedures, 13 patients (0.38%, mean age 57 ± 8, 6 female, 12 paroxysmal AF, mean left atrial diameter 35.4 ± 3.8 mm) had STE. ST-T elevation occurred after transseptal puncture in 10 patients and after pulmonary vein venography in three patients. Systolic blood pressure (129 ± 10 vs. 104 ± 20 mmHg, P < 0.001), diastolic blood pressure (78 ± 6 vs. 64 ± 11 mmHg, P < 0.001), and heart rate (83 ± 19 bpm vs. 64 ± 23 b.p.m., P = 0.022) significantly decreased when STE occurred. Eleven patients complained of chest pain, one patient complained of dizziness, and one patient had no symptoms. Patients recovered in about 4.6 min (2-10 min) with dopamine or fast saline drip. Catheter ablation of AF was completed in all the 13 patients without sequelae or other complications. Four of the 13 patients (30.8%) had recurrence of AF after a mean follow-up of 21.7 months. CONCLUSION: ST-T elevation is a rare complication associated with transseptal catheterization without sequelae. Catheter ablation of AF could be safely completed in these patients.

Correlations of MUC15 overexpression with clinicopathological features and prognosis of glioma / 华中科技大学学报（医学）（英德文版）

The abnormal expression of MUC15, a novel cell membrane-associated mucin, has been reported to predict poor survival in several cancers. The aim of the present study was to examine the expression of MUC15 in glioma and its correlation with clinicopathological features, including the survival of patients with glioma. The mRNA expression level of MUC15 was determined by RT-PCR, quantitative RT-PCR (RT-qPCR) and Western blotting in seven normal brain tissues and seven glioma tissues, respectively. The protein expression level of MUC15 was immunohistochemically detected in paraffin-embedded samples of 317 glioma tissues and 115 noncancerous brain tissues. The association of MUC15 expression levels with the clinicopathologic features and the prognosis was analyzed. The results showed that both mRNA and protein levels of MUC15 were significantly increased in glioma as compared with those in noncancerous brain tissue. Moreover, MUC15 overexpression was positively correlated with the advanced clinical stages of glioam patients (P<0.01). Furthermore, MUC15 expression levels were significantly correlated with the progression of glioma (P<0.001). Survival analysis indicated that glioma patients with higher MUC15 expression had a significantly shorter overall and 5-year survival time than those with low MUC15 expression. Multivariate analysis suggested that MUC15 overexpression was an independent factor for prognosis (hazard risk: 3.216; P=0.009). It was concluded that MUC15 is overexpressed in glioma tissues. Its overexpression correlates with tumor progression and it is a potentially unfavorable prognostic factor for patients with glioma.

Correlations of MUC15 overexpression with clinicopathological features and prognosis of glioma / 华中科技大学学报（医学）（英德文版）

The abnormal expression of MUC15, a novel cell membrane-associated mucin, has been reported to predict poor survival in several cancers. The aim of the present study was to examine the expression of MUC15 in glioma and its correlation with clinicopathological features, including the survival of patients with glioma. The mRNA expression level of MUC15 was determined by RT-PCR, quantitative RT-PCR (RT-qPCR) and Western blotting in seven normal brain tissues and seven glioma tissues, respectively. The protein expression level of MUC15 was immunohistochemically detected in paraffin-embedded samples of 317 glioma tissues and 115 noncancerous brain tissues. The association of MUC15 expression levels with the clinicopathologic features and the prognosis was analyzed. The results showed that both mRNA and protein levels of MUC15 were significantly increased in glioma as compared with those in noncancerous brain tissue. Moreover, MUC15 overexpression was positively correlated with the advanced clinical stages of glioam patients (P<0.01). Furthermore, MUC15 expression levels were significantly correlated with the progression of glioma (P<0.001). Survival analysis indicated that glioma patients with higher MUC15 expression had a significantly shorter overall and 5-year survival time than those with low MUC15 expression. Multivariate analysis suggested that MUC15 overexpression was an independent factor for prognosis (hazard risk: 3.216; P=0.009). It was concluded that MUC15 is overexpressed in glioma tissues. Its overexpression correlates with tumor progression and it is a potentially unfavorable prognostic factor for patients with glioma.

Screening for novel protein targets of indomethacin in HCT116 human colon cancer cells using proteomics.

Non-steroidal anti-inflammatory drugs, such as indomethacin (IN), inhibit colorectal cancer (CRC) growth through cyclooxygenase (COX)-independent mechanisms, however, the precise biological mechanisms are not completely understood. The aim of the present study was to investigate new molecular factors potentially associated with IN in HCT116 human CRC cells, which do not express COX, using a proteomic approach. The total proteins from the IN-treated and untreated groups were separated by immobilized pH gradient-based two-dimensional gel electrophoresis. The differentially-expressed proteins were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry. The PMF maps were searched in the SWISS-PROT/TrEMBL database using the PeptIdent software. Between the IN-treated and untreated groups, a total of 45 differential protein spots were detected and 15 differentially-expressed proteins were identified by PMF. IN downregulated Wnt1-inducible signaling pathway protein 1, Bcl-2-related protein A1 and mitogen-activated protein kinase, inhibited HCT116 cell growth and induced apoptosis. In conclusion, IN may exert its effects on CRC to induce HCT116 cell apoptosis and suppress growth through COX-independent pathways.

Assessing heat-related mortality risks in Beijing, China.

OBJECTIVE: To obtain the exposure-response relationship for temperature and mortality, and assess the risk of heat-related premature death. METHODS: A statistical model was developed using a Poisson generalized linear regression model with Beijing mortality and temperature data from October 1st, 2006 to September 30th, 2008. We calculated the exposure-response relationship for temperature and mortality in the central city, and inner suburban and outer suburban regions. Based on this relationship, a health risk model was used to assess the risk of heat-related premature death in the summer (June to August) of 2009. RESULTS: The population in the outer suburbs had the highest temperature-related mortality risk. People in the central city had a mid-range risk, while people in the inner suburbs had the lowest risk. Risk assessment predicted that the number of heat-related premature deaths in the summer of 2009 was 1581. The city areas of Chaoyang and Haidian districts had the highest number of premature deaths. The number of premature deaths in the southern areas of Beijing (Fangshan, Fengtai, Daxing, and Tongzhou districts) was in the mid-range. CONCLUSION: Ambient temperature significantly affects human mortality in Beijing. People in the city and outer suburban area have a higher temperature-related mortality risk than people in the inner suburban area. This may be explained by a temperature-related vulnerability.

Transient ST-segment elevation after transseptal puncture for atrial fibrillation ablation in two cases.

The present report demonstrates two cases of transient inferior ST-segment elevation accompanied by profound hypotension and bradycardia immediately after transseptal puncture for catheter ablation of atrial fibrillation. This rare complication of transseptal puncture was resolved quickly within several minutes. The most likely mechanism of this phenomenon is coronary vasospasm, although coronary embolism can not be ruled out completely. This complication is characterized as follows: (1) The right coronary artery might be the most likely involved vessel and therefore myocardial ischemia usually occurs in the inferior wall of left ventricular; (2) Reflex hypotension and bradycardia by the Bezold-Jarisch reflex secondary to inferior ischemia often occur at the same time. Though it appears to be a transient and completely reversible phenomenon, there are still potential life-threatening risks because of myocardial ischemia and profound haemodynamic instability. Clinical cardiologists should be aware of this rare complication and properly deal with it.

[Prediction of heat-related mortality impacts under climate change scenarios in Shanghai].

OBJECTIVE: To project the future impacts of climate change on heat-related mortality in shanghai. METHODS: The statistical downscaling techniques were applied to simulate the daily mean temperatures of Shanghai in the middle and farther future under the changing climate. Based on the published exposure-reaction relationship of temperature and mortality in Shanghai, we projected the heat-related mortality in the middle and farther future under the circumstance of high speed increase of carbon e mission (A2) and low speed increase of carbon emission (B2). The data of 1961 to 1990 was used to establish the model, and the data of 1991 - 2001 was used to testify the model, and then the daily mean temperature from 2030 to 2059 and from 2070 to 2099 were simulated and the heat-related mortality was projected. The data resources were from U.S. National Climatic Data Center (NCDC), U.S. National Centers for Environmental Prediction Reanalysis Data in SDSM Website and UK Hadley Centre Coupled Model Data in SDSM Website. RESULTS: The explained variance and the standard error of the established model was separately 98.1% and 1.24°C. The R(2) value of the simulated trend line equaled to 0.978 in Shanghai, as testified by the model. Therefore, the temperature prediction model simulated daily mean temperatures well. Under A2 scenario, the daily mean temperature in 2030 - 2059 and 2070 - 2099 were projected to be 17.9°C and 20.4°C, respectively, increasing by 1.1°C and 3.6°C when compared to baseline period (16.8°C). Under B2 scenario, the daily mean temperature in 2030 - 2059 and 2070 - 2099 were projected to be 17.8°C and 19.1°C, respectively, increasing by 1.0°C and 2.3°C when compared to baseline period (16.8°C). Under A2 scenario, annual average heat-related mortality were projected to be 516 cases and 1191 cases in 2030 - 2059 and 2070 - 2099, respectively, increasing 53.6% and 254.5% when compared with baseline period (336 cases). Under B2 scenario, annual average heat-related mortality were projected to be 498 cases and 832 cases in 2030 - 2059 and 2070 - 2099, respectively, increasing 48.2% and 147.6% when compared with baseline period (336 cases). CONCLUSION: Under the changing climate, heat-related mortality is projected to increase in the future;and the increase will be more obvious in year 2070 - 2099 than in year 2030 - 2059.