[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

[Analysis of etiology and complications in children with stage 5 chronic kidney disease].

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.

[Research advances on venous thromboembolism in burn patients].

Venous thromboembolism (VTE) has become a serious medical problem faced by medical personnel all over the world, due to its high incidence, high fatality, and easily missed and misdiagnosed. Patients with severe burns are at high risk for VTE due to the presence of blood hypercoagulability, central venous catheterization, repeatedly received surgical procedures, and prolonged bed rest. Identifying the risk factors of VTE in burn patients and taking targeted preventive measures are the key to reduce the incidence of VTE. However, there are no risk assessment tools or prevention guidelines for VTE in burn patients at home and abroad, and scholars from various countries are actively exploring the occurrence, influencing factors, and prevention of VTE in burn patients. This paper reviews the research progress of the occurrence situation, related risk factors, risk assessment, and prevention of VTE in burn patients in recent years, and discusses the existing problems and future research directions in this field.

[The relationships between functional gastrointestinal diseases and psychological factors, diet and lifestyles: a network analysis].

Objective: To investigate the relationship between common functional gastrointestinal diseases symptoms with psychological factors, diet and lifestyles by using the network analysis method which has achieved great success in the field of psychology in recent years. Method: A questionnaire survey was conducted in two military units using the cluster sampling method during July 2020, and a total of 1 805 subjects were included. Functional gastrointestinal disease symptoms were evaluated with the Gastrointestinal Symptom Rating Scale (GSRS). The state, trait anxiety scale and stress response scale were used to evaluate the mental and psychological state by self-evaluation. R was used to build the network and calculate statistical parameters. Results: 1 486 of the 1 805 subjects (82.3%) had experienced functional gastrointestinal diseases symptoms within 2 weeks, but most of them were mild. Network analysis shows that there was a strong interaction between digestive system symptoms with different clinical manifestations (Spearman coefficient ranges 0.31-0.56). There was a clear relationship between functional gastrointestinal symptoms and mental and psychological factors (Spearman coefficient ranges 0.16-0.27), but there was no clear interaction with diet, age, education level, body mass index, etc. Functional gastrointestinal diseases symptoms were connected with mental and psychological factors through two nodes: stress and indigestion. The stability coefficient of node strength correlation was 0.75, indicating that the network was stable. Conclusions: The current study revealed the network structure and features of functional gastrointestinal diseases symptoms with mental and psychological factors. The key linking nodes provided potential interfering target for controlling functional gastrointestinal symptoms related to mental and psychological factors.

Insurance status and risk of suicide mortality among patients with cancer: a retrospective study based on the SEER database.

OBJECTIVE: Given that the presence of insurance may affect the risk of suicide mortality in cancer patients, we aimed to examine the association in a population-based study using the Surveillance, Epidemiologic, and End Results (SEER) database. STUDY DESIGN: A retrospective analysis of data from the SEER database. METHODS: We conducted a retrospective study using the SEER database. Hazard ratios (HRs), adjusted HRs (aHRs), and 95% confidence intervals (95% CIs) of suicide death were calculated using Cox proportional hazard models to evaluate the risk of suicide mortality among the cohorts. RESULTS: Multivariable analysis revealed that cancer patients without insurance had an increased risk of suicide death compared with patients with private insurance (aHR, 1.37; 95% CI, 1.01-1.72), whereas no significant result was observed in patients with any Medicaid (aHR, 1.10; 95% CI, 0.93-1.30; P = 0.27). In addition, the stratified analysis indicated that the risk of suicide death in patients in the uninsured and Medicaid groups presented with localized stage of disease (aHR, 1.32; 95% CI, 1.02, 1.69), White (aHR, 1.34; 95% CI, 1.05, 1.71), and American Indian/Alaska Native and Asian/Pacific Islander (aHR, 1.89; 95% CI, 1.08, 3.30) were greater than insured patients. CONCLUSION: Overall, our results indicated that insurance status was a statistically significant predictor of suicide death in patients with cancer. Healthcare providers should identify those patients at high risk of suicide and provide appropriate mental health and psychosocial oncology services in time.

[Efficacy and safety of Changsulin® compared with Lantus® in type 2 diabetes: a phase â ¢ multicenter, randomized, open-label, parallel, controlled clinical trial].

Objective: To compare the efficacy and safety of Changsulin® with Lantus® in treating patients with type 2 diabetes mellitus (T2DM). Methods: This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin® or Lantus® treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results: After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin® and in Lantus®, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin® and Lantus® in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin® and Lantus®, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin® and Lantus®, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions: Changsulin® shows similar efficacy and safety profiles compared with Lantus® and Changsulin® treatment was well tolerated in patients with T2DM.

[Clinical characteristics and survival analysis of primary intestinal extranodal NK/T-cell lymphoma, nasal type].

Objective: To retrospectively analyze the clinical features and survival analysis of primary intestinal extranodal NK/T-cell lymphoma nasal type(ENKTL). Methods: Patients with intestinal lymphoma at the First Affiliated Hospital of Air Force Military Medical University were collected from January 2009 to December 2019, and those with primary intestinal ENKTL screened. The general situation, main symptoms, ECOG scale, lactic dehydrogenase(LDH), and ß(2)-microglobulin(ß(2)-MG)in the serum, lesion site and form, numbers of extranodal invasion, Lugano stage, pathological features, and lifetime and survival outcomes were evaluated. Results: In total, 34 patients with confirmed diagnosis of primary intestinal ENKTL were identified. The incidence rate of primary intestinal ENKTL is 16.2% (34/210). A total of 26 patients were men and 8 were women with the median age at diagnosis of 45 (range, 20-69)years and patients younger than 60 years account for 85.3%. It included abdominal pain (76.5%), diarrhea(20.6%), hematochezia(29.4%), and abdominal mass(2.9%), 85.3% with B-symptoms, and abnormally elevated LDH in the serum(73.5%). The lesion sites included large intestine(52.9%), small intestine(29.4%), and both of them(17.7%). The lesion forms were featured by mass(8.8%), ulcer(32.4%), diffuse infiltration(2.9%), and hybrid(55.9%). Lugano stage included stage Ⅰ/Ⅱ (70.6%)24 patients and stage Ⅳ(29.4%)10 patients. About 94.1% patients were EBER positive. The median survival time was 60 days. The overall survival rate had significant differences on ECOG scale, LDH in the serum, IPI score and complications(P=0.037, 0.009, 0.002, and 0.000, respectively). Conclusion: Primary intestinal ENKTL was commonly observed in men at young or middle age, and the most common symptom was abdominal pain, often with B-symptoms, abnormally elevated LDH in the serum. The most common site was the large intestine. The lesion forms were mainly featured by the hybrid and ulcer. It seemed that patients with IPI low-risk group and without any complication would have longer survival time.

[Clinical and genetic characteristics of 62 children with mitochondrial epilepsy].

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ(2) test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ(2)=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions: The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

[A preliminary study on resting-state functional magnetic resonance imaging of brain after anterior cruciate ligament preservation reconstruction with autologous tendon].

Objective: To preliminarily study on the possible mechanism of cerebral cortical dysfunction pattern after anterior cruciate ligament (ACL) preservation reconstruction with autologous tendon through resting-state functional magnetic resonance imaging (fMRI). Methods: From June 2015 to February 2019, 18 patients (10 males and 8 females with an average age of (36±10) years) with left anterior cruciate ligament rupture and treated with arthroscopic preservation reconstruction with autologous tendon were enrolled in this study, and 17 comparable healthy controls were included in Tongji Hospital of Tongji University. fMRI was performed after the postoperative period (2 to 12 weeks). The fMRI data were preprocessed by SPM8 software package and RESTplus software. The amplitude of low-frequency fluctuation (ALFF) and the fractional amplitude of low-frequency fluctuation (fALFF) in those two groups were calculated. Two-sample t-test was performed on ALFF and fALFF of the two groups, and multiple test corrections were performed by using AlphaSim. These methods were used for contrast studies on the characteristic activities of the brain dysfunction. Results: Compared with those in the control, ALFF in the central cingulate gyrus (cingulum_mid_bilateral), involving the auxiliary movement zone (supp_motor_ area) were significantly higher in the patients (P<0.01 before correction, P<0.05 after AlphaSim correction). The fALFF in activation cluster 1 was significantly higher in the right central gyrus (postcentral_R), the right lower lobule (parietal_inf_R), and the right upper margin (supramarginal_R) in the patients than that in the normal control group, respectively (P<0.01 before correction, P<0.05 after AlphaSim correction); the fALFF in activation cluster 2 in the right central cingulate gyrus (cingulum_mid_R), involving the right auxiliary movement zone (supp_motor_area_R) was significantly higher in the patients than that in the normal control group, respectively (P<0.01 before correction, P<0.05 after AlphaSim correction). Conclusion: The patients' cerebrum cortical function associated with the kinesthesis and their regulations are abnormally changed after anterior cruciate ligament preservation reconstruction with autologous tendon.

[Normal values for solid state high resolution anorectal manometry in healthy adult volunteers].

Objective: To explore the normal values for two-dimension solid state high resolution anorectal manometry (HRAM) in healthy adult volunteers. Methods: The healthy adult volunteers were recruited by advertisement and underwent solid state HRAM in the left lateral position. Anorectal pressures and rectal sensation were recorded and analyzed. Results: (1) A total of 126 Chinese healthy adult volunteers (male: 50 cases (39.7%); age: (37.5±14.2) years old ) were recruited in this study. (2) Mean anal resting pressure (MERP) was (71.8±17.3) mmHg (1 mmHg=0.133 kPa). Maximum anal resting pressure (MARP) was (79.3±17.8) mmHg, Maximum anal squeeze pressure (MSP) was (178.7±52.8) mmHg. Anal high pressure zone (HPZ) length was (3.4±0.6) cm. During simulated evacuation, residual anal pressure (RAP) was (63.8±20.5) mmHg, and anal relaxation rate (ARR) was (37.0±11.5)%. Rectal threshold volume for first sensation (FST), desire to defecate (DDT), urgency to defecate (UDT) and maximum discomfort (MDT) was (47.4±10.0) ml, (84.5±18.2) ml, (125.8±28.5) ml, and (175.5±36.1) ml, respectively. (3) Compared with female subjects, male subjects had higher MSP[(211.0±50.7) mmHg vs (157.5±42.5) mmHg], RAP[(71.6±18.1) mmHg vs (58.8±20.5) mmHg]and rectal MDT[(187.0±36.4) mmHg vs (168.0±34.1)mmHg], but lower ARR[(32.1±8.0)% vs (40.2±12.3)%], all P<0.01. (4) MERP, MARP, MSP and rectal MDT were higher in young group (≤40 years old), all P<0.05. Conclusions: These observations provide normal values for two-dimension solid state HRAM, which have significant difference between genders and different age groups.

Serum vitamin D level is associated with disease severity and response to ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Serum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in various autoimmune and liver diseases. AIM: To investigate the clinical relevance of vitamin D levels in PBC, especially their association with the therapeutic effects of ursodeoxycholic acid (UDCA). METHODS: Consecutive PBC patients were retrospectively reviewed. 25-hydroxyvitamin D [25(OH)D] levels were determined in frozen serum samples collected before initiation of UDCA treatment. Response to UDCA was evaluated by Paris-I and Barcelona criteria. Logistic regressions were performed to identify the treatment response-associated parameters. RESULTS: Among 98 patients, the mean serum 25(OH)D concentration was 17.9 ± 7.6 ng/mL. 25(OH)D levels decreased with increasing histological stage (P = 0.029) and were negatively correlated with bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31 patients failed to achieve complete response according to Paris-I criteria. The baseline 25(OH)D level was significantly lower in nonresponders (14.8 ± 6.4 vs. 19.3 ± 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated with an increased risk of incomplete response independent of advanced stages (OR = 3.93, 95% CI = 1.02-15.19, P = 0.047). Similar results were obtained when biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D levels were lower in patients who subsequently suffered death or liver transplantation (12.1 ± 4.6 vs. 18.4 ± 7.6 ng/mL, P = 0.023). CONCLUSIONS: 25(OH)D level is associated with biochemical and histological features in PBC. Pre-treatment vitamin D status is independently related to subsequent response to UDCA. Our results suggest that vitamin D status may have important clinical significance in PBC.

MicroRNA-296-5p increases proliferation in gastric cancer through repression of Caudal-related homeobox 1.

Caudal-related homeobox 1 (CDX1), an intestinal-specific transcription factor, has been reported to have vital roles in gastric intestinal metaplasia (IM). Although IM is a high-risk factor for gastric cancer (GC), the specific role of CDX1 in GC is largely unknown. In this study, we investigated the expression of CDX1 and its functional roles in GC, and its upstream regulatory mechanisms at the microRNA (miRNA) level were further explored. We found that CDX1 is lost in GC when compared with adjacent IM tissues. Gain-of-function studies showed that CDX1 significantly inhibited GC cell growth by inducing cell cycle arrest and apoptosis. Interestingly, we identified and verified an onco-mir, miR-296-5p, as a direct upstream regulator of CDX1. miR-296-5p overexpression significantly promoted GC cell growth and attenuated the CDX1-induced anti-growth effects by recurring cell cycle distribution and apoptotic status, whereas knockdown of miR-296-5p decreased GC cell growth. Furthermore, we found that the extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation and the subsequent downstream changes in protein levels related to cell cycle and apoptosis partly account for the miR-296-5p-CDX1-induced GC growth promotion. In addition, the detection of miR-296-5p and expression of CDX1 in primary GC tissues and adjacent IM tissues revealed that miR-296-5p is inversely correlated with CDX1, further supporting our in vitro results. Our results showed an anti-growth effect of CDX1 and identified its miRNA regulatory mechanism in GC. The identification of this novel miR-296-5p-CDX1-ERK1/2 axis sheds new light on the understanding of the process from IM to GC and may provide therapeutic targets for the treatment of GC.

Clinicopathological features and prognostic factors of rectal gastrointestinal stromal tumors.

AIM: Rectal gastrointestinal stromal tumor (GIST) was a rare disease. This study sought to summarize clinicopathological features and prognostic factors of rectal GISTs. METHODS: Clinicopathological characteristics and prognostic factors of rectal GISTs were investigated by reviewing patients undergoing curative resection at the Fudan University Shanghai Cancer Center between 1986 and 2010. RESULTS: Twenty-one patients, 15 male and 6 female, were included. The mean age of onset was 51 years. The most common initial presentation was hematochezia (7 cases). Eleven patients underwent radical resection, and the other 10 received local resection. No lymph node metastases were identified. All cases were positive for CD117. Seventeen patients were classified as high National Institutes of Health (NIH) risk category. The 5-year disease-free survival (DFS) and overall survival were 33 and 46 %, respectively. Fifteen cases had recurrence postoperatively. Both univariate and multivariate analyses demonstrated the NIH risk category (p = 0.028) and hematochezia symptom (p = 0.014) were independent prognostic factors of the DFS of patients. CONCLUSIONS: Hematochezia was the most common initial symptom. Over 50 % of patients received radical surgery. More than 80 % of patients were at high NIH risk of recurrence. Hematochezia symptom and high NIH risk category indicated poor prognosis of rectal GISTs.

Combination therapy with metformin and fenofibrate for insulin resistance in obesity.

This randomized controlled study investigated metformin and fenofibrate, compared with metformin alone, for the treatment of peripheral insulin resistance in patients with simple obesity with hyperinsulinaemia but not diabetes. Participants were randomized to receive metformin (500 mg orally three times daily) plus either fenofibrate (200 mg orally once daily; n = 44) or placebo (n = 43) for 6 months. Blood pressure, free fatty acids (FFA), body mass index (BMI), lipid and insulin levels were recorded pre- and post-treatment. ß-Cell function and insulin resistance were measured by the homeostasis model assessment for insulin resistance (HOMA-IR) index. Both groups showed significant decreases in blood pressure, FFA, BMI and HOMA-IR relative to baseline. In addition, combined metformin and fenofibrate therapy showed significantly decreased fasting and postmeal insulin levels relative to baseline and relative to the placebo group. Both treatments were well tolerated. Metformin and fenofibrate can increase insulin sensitivity and recover ß-cell function in patients with simple obesity accompanied by insulin resistance.

Increased expression of phosphorylated Smad2 and Smad3 in the hippocampus of streptozotocin-induced diabetic rats.

Activation of the Smad signalling pathway has been implicated in the pathological process of diabetic associated complications. The current study was designed to see whether Smad signalling was activated in the hippocampus of streptozotocin-induced diabetic rats. Compared with vehicle-treated controls, immunoblot analysis of hippocampal extracts showed that phosphorylated Smad2 was upregulated at 8 weeks post streptozotocin induction (p<0.01), and phosphorylated Smad3 protein was upregulated at 4 and 8 weeks post streptozotocin induction (p<0.01) in streptozotocin-induced diabetic rats. In addition, immunofluorescence labelling assay showed that the percentage of pSmad2 immunoreactive astrocytes increased significantly in CA1, CA3 and dentate gyrus region (p<0.01), and pSmad3 immunoreactive astrocytes increased significantly in CA1 region (p<0.01) and in CA3 and dentate gyrus region (p<0.05) of the hippocampus in diabetic rats. These data indicate that Smad signalling is enhanced in hippocampal astrocytes of diabetic rats, and may thereby represent a clue to explore its exact role in the development of diabetic encephalopathy.