Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

OBJECTIVETo evaluate the influences of inferior mesenteric artery (IMA) types and Riolan artery arcade absence on the incidence of anastomotic leakage(AL) after laparoscopic resection of rectal cancer.

METHODSClinical data of 116 local advanced rectal cancer patients who underwent laparoscopic resection in The Sixth Affiliated Hospital of Sun Yat-sen University from January 2012 to December 2014 were analyzed retrospectively. IMA and Riolan artery arcade were examined by preoperative computed tomography angiography (CTA) reconstruction. The influences of IMA type, Riolan artery arcade absence and ligation site (high or low) on AL were analyzed by Logistic regression.

RESULTSThe proportion of IMA types(I(-IIII() was 57.8%(67/116), 10.3%(12/116), 31.0%(36/116) and 0.9%(1/116), respectively. Riolan artery arcade absence was found in 60.3%(70/116). Eight (6.9%) patients suffered from AL. IMA type III( had significantly higher AL incidence as compared to other IMA types [19.4%(7/36) vs. 1.2%(1/80), P=0.001]. Meanwhile, patients with Riolan artery arcade absence also had significantly higher AL incidence[11.4%(8/70) vs. 0.0%(0/46), P=0.030]. However, the difference in AL incidence between high and Low IMA ligation was not statistically significant [8.0%(7/87) vs. 3.4%(1/29), P=0.531]. Seven of these 8 AL patients were found in IMA type III( with Riolan artery arcade absence and high ligation. Multivariate analysis showed that IMA type III( (P=0.001) and Riolan artery arcade absence (P=0.002) were independent risk factors of AL.

CONCLUSIONSIMA type III( with Riolan artery arcade absence increases AL incidence significantly in laparoscopic resection of rectal cancer. IMA type and Riolan aretry arcade absence or not contribute to the selection of IMA ligation site in the operation. For the colorectal cancer patients with IMA type III( and Riolan artery arcade absence, selective low IMA ligation with root lymph node dissection should be recommended.

Adult ; Anastomotic Leak ; Arteries ; Colorectal Neoplasms ; surgery ; Female ; Humans ; Incidence ; Laparoscopy ; Ligation ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Mesenteric Artery, Inferior ; Middle Aged ; Rectal Neoplasms ; surgery ; Retrospective Studies

OBJECTIVETo evaluate the long-term clinical outcomes between laparoscopic and open distal gastrectomy with D2 lymph dissection for advanced gastric cancer.

METHODSClinical data of 377 cases of laparoscopic distal gastrectomy and 301 cases of open distal gastrectomy with D2 lymph dissection at the Southwest Hospital, the Third Military Medical University from January 2004 to June 2010 were retrospectively analyzed. Patients were followed up until September 2015. Surgical outcomes, postoperative complications and long-term survival were compared between the two groups.

RESULTSCompared with conventional open group, laparoscopic group was associated with lower intraoperative blood loss [(125±89) ml vs. (290±161) ml, t=-15.942, P=0.000], shorter time to oral intake [(2.9±0.7) days vs. (4.1±1.6) days, t=-12.120, P=0.000], quicker bowel function retum[(2.7±1.4) days vs. (3.6±1.6) days, t=-7.804, P=0.000], shorter postoperative hospital stay [(7.7±3.6) days vs. (10.1±4.1) days, t=-8.107, P=0.000]. In addition, there were no significant differences in the operative time[(207±57) minutes vs. (202±43) minutes, P>0.05], number of retrieved lymph nodes(33±13 vs. 31±15, P>0.05), resection margin length(P>0.05) between two groups. The postoperative complication morbidity in laparoscopic group was significantly lower than that in open group[7.2%(22/377) vs. 12.6%(38/301), χ(2)=5.762, P=0.016]. Within perioperative period, 7 patients underwent operation again due to complication and 1 case died of peritoneal bleeding in laparoscopic group; 6 patients underwent re-operation and 2 cases died of peritoneal infection with hepatic failure and lung infection with respiratory failure. During the median follow-up of 86 months (range from 3-140 months), relapse occurred in 171(45.4%) patients and 183(48.5%, among them, 156 cases died of primary disease) patients died in laparoscopic group; relapse occurred in 140(46.5%) patients and 151(50.2%, among them, 127 cases died of primary disease) patients died in open group. The difference in overall 5-year survival rate between two groups was not statistically significant (51.5% vs. 49.8%, χ(2)=0.142, P=0.706). No significant difference was seen in 5-year disease-free survival rate (49.1% vs. 47.8%, χ(2)=0.062, P=0.803). Stratified analysis based on TNM stage also showed no significant difference in 5-year overall or disease-free survival rate(both P>0.05).

CONCLUSIONLaparoscopic distal gastrectomy with D2 lymph dissection for advanced gastric cancer has better short-term efficacy and similar long-tern efficacy as compared to open surgery.

Blood Loss, Surgical ; Defecation ; Disease-Free Survival ; Gastrectomy ; methods ; Gastroenterostomy ; Humans ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Neoplasm Recurrence, Local ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Survival Rate ; Treatment Outcome

Multidrug resistance proteins (MRP2, ABCC2) may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCC2 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. ABCC2 rs717620, rs2273697, rs3740066 polymorphisms were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 80 patients treated with CBZ monotherapy. There were no differences in CBZ maintenance doses or adjusted plasma CBZ concentrations among the ABCC2 rs717620, rs2273697 and rs3740066 genotypic groups. No associations between all the studied genotypes and haplotypes involving the three SNPs of ABCC2 and CBZ resistance were observed in this patient cohort. These results suggest that ABCC2 polymorphisms may not contribute to interindividual variabilities in CBZ daily maintenance doses, plasma concentrations, and treatment efficacy.
Epilepsy

Objective To evaluate the relationship between birth weight and nonalcoholic fatty liver diseases (NAFLD) in Chinese primary school students. Methods A cross-section study was conducted in ifve elementary schools in Gao Hang Town, Shanghai and 2163 students were enrolled in the study (1120 boys/1043 girls). Height, body weight, waist circumference and per-cent of body fat (bioelectrical impedance analysis) were measured by professional nutritionist after training. Birth weight, feeding pattern, height and body weight of parents were obtained by a self-completed questionnaire. NAFLD was diagnosed by ultra-sound. The risk factors of NAFLD were analyzed. Results The prevalence of NAFLD in the study population was 8.9%. The prevalence of NAFLD was signiifcantly higher in boys than that in girls (12.5%vs 5.0%, P<0.01). Logistic regression showed that sex (OR=1.97, 95%CI:1.21-3.21) and percent of body fat (OR=1.12, 95%CI:1.07-1.17) were the risk factors of NAFLD, and normal BMI was the protective factor of NAFLD (OR=0.09, 95%CI:0.04-0.19) in the study population. Conclusions The pre-valence of NAFLD is higher in boys than that in girls. Also overweight, and high percent of body fat are risk factors of NAFLD in children.

Objective Evaluation the Fractionated Stereotactic Radiotherapy (FSRT) for the patients with small-cell lung cancer (SCLC) after the whole brain radiotherapy (WBRT) failure.Methods We retrospectively analyzed 35 patients with brain metastases from small-cell lung cancer treated with linear accelerator FSRT after the WBRT failure. Multivariate analysis was used to determine significant prognostic factor related to survival.ResultsThe following-up rate was 100％.The median following-up time was 11 months.The median over-all survival (OS) time was 10.3( 1 -30) months after FSRT.Controlled extra cranial disease was the only identified significant predictor of increased median OS time (χ2 =4.02,P =0.045 ).The median OS time from the diagnosis of brain metastasis was 22 (6 - 134 )months.14 patients died from brain metastasis,14 from extra-cranial progression,1 from leptomeningeal metastases,and 3 from other causes. Local control at 6 months and 12 months was 91％ and 76％,respectively.No significant late complications.New brain metastases outside of the treated area developed in 17％ of patients at a median time of 4(2 -20) months; all patients had received previous WBRT.ConclusionsFractionated stereotactic radiotherapy was safe and effective treatment for recurrent small-cell lung carcinoma brain metastases.

This study was undertaken to elucidate the degradation regularity of calcium polyphosphate (CPP) scaffolds with different preparation parameters. CPP scaffolds with different main crystalline phases were prepared by controlling the particle size of the calcining stuff and the calcining heat. Specimens were soaked into Tris-buffer solution and simulated body fluid (SBF) for 60 days. Results show: alpha-CPP degrades faster than does beta-CPP, and beta-CPP degrades faster than does gamma-CPP; the lower the sinter temperature, the better the degradation of CPP morever, the degradation rate of CPP is inversely proportional to the original particle size. These data suggest that crystal type, sinter temperature and particle size influence the degradation rate of CPP markedly.
Absorbable Implants ; Biocompatible Materials ; chemistry ; Bone Substitutes ; chemistry ; Calcium ; chemistry ; Calcium Phosphates ; chemistry ; Ceramics ; chemistry ; Polymers ; chemistry ; Polyphosphates ; chemistry ; Tissue Scaffolds ; chemistry

Objective To study the roles of dengue (DEN) virus specific T cells in the pathogenesis of DEN virus infection. Methods 2D42 cells, DEN virus specific CD8 + cell clones, were employed to investigate their in vivo function in DEN virus infection using an animal model. HepG2 was implanted into mice with severe combined immunodeficiency disease (HepG2-SCID) for the establishment of HepG2-SCID model. The animals were divided into 3 groups: Group A: HepG2-SCID mice were inoculated with 2D42 cells and then infected with DEN virus type 2 (DEN2) intraperitoneally; Group B: HepG2-SCID mice were inoculated with normal mouse thymuscytes (NMT) and then intraperitoneally infected with DEN2; Group C: HepG2-SCID mice were intraperitoneally infected with DEN2 alone. The mortality, viremia, and frequency of histopathological changes in the major organs of mice in the three groups were observed after infection. Results After inoculation of 2D42 cells, 80% infected mice showed severe clinical signs and died at the average 12.8 d after infection. The others only had transient manifestations, and then recovered from the disease and survived for more than 3 months. In contrast, after inoculation of NMT and /or DEN2 alone, 100% mortality rate was noted in these two groups. High viremia and frequency of histopathological changes in the major organs were observed in the mice in groups A and B. Conclusion Our data support both protective and pathogenic roles for DEN-specific CD8 + T cells in DEN virus infection.