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.

Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

Objective:To investigate the adverse reactions and postoperative inflammatory reactions of Bill-Roth Ⅱ (BⅡ) gastroenterostomy with jejunal anastomosis and jejunal nutrient tube placement using linear cutting and closing device in gastric cancer surgery.Methods:A retrospective case-control study was conducted on 93 patients undergoing gastric cancer surgery in The Affiliated Hospital of North China University of Science and Technology from February 2017 to April 2020. According to 2016 (American Joint Committee on Cancer/Universal Integrated Circuit Card) AJCC/UICC, (Tumor, Node, stage; Tumor lymph node metastasis; Distant metastasis) TNM, there were 11 cases in stage ⅠA, 14 cases in stage ⅠB, 13 cases in stage ⅡA, 15 cases in stage ⅡB, 11 cases in stage ⅢA, 13 cases in stage ⅢB, and 16 cases in stage ⅢC. There were 51 cases of gastric antrum carcinoma, 26 cases of gastric body carcinoma and 16 cases of gastric pylorus carcinoma. There were 27 cases of papillary adenocarcinoma, 26 cases of tubular adenocarcinoma, 22 cases of mucinous adenocarcinoma, 9 cases of signet-ring cell carcinoma, 7 cases of adenosquamous carcinoma, and 2 cases of squamous carcinoma. The patients were divided into experimental group (48 cases) and control group (45 cases) according to whether or not the linear cutting and closing device was added and jejunal anastomosis was performed and jejunal nutrition tube was placed. The gender composition, age, lesion site, pathological type, pathological stage, postoperative hospital stay and postoperative complications were compared between the two groups, and the white blood cell count WBC, C-reactive protein CRP on the 7th day after surgery, erythrocyte Sedimentation rate (ESR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) inflammation indicators were compared between the two groups.Results:There was no significant difference in gender composition, age, lesion location, pathological type and pathological stage between the two groups (all P>0.05). The incidence of abdominal pain, abdominal distension, nausea, vomiting and pleural effusion in 93 patients were 18.3%(17/93), 21.5%(20/93), 23.7%(22/93), 17.2%(16/93) and 18.3%(17/93), respectively. The complication rates of the above indexes in the two groups were 10.4% (5/48) Compared with 26.7% (12/45), 12.5% (6/48) and 31.1% (14/45), 15.6%(7/48) and 33.3% (15/45), 8.3%(4/48) and 26.7% (12/45), 8.3% (4/48) and 28.9% (13/45) (χ 2 values were 4.11, 4.77, 4.52, 4.27 and 5.27, respectively; P values were 0.043, 0.029, 0.033, 0.039 and 0.022, respectively). There was no significant difference in lower extremity venous thrombosis, anastomotic bleeding, accumulated pneumonia and incision dehiscence between the two groups ( P>0.05). WBC on the 7th day after operation in the experimental group and the control group (7.02±1.83)×10 9/L and (8.39±2.27)×10 9/L ( t=3.22, P=0.002), TNF-α (2.44±0.70) μg/L and (3.56±1.14) μg/L ( t=5.71, P<0.001), IL-6 (235.31±41.72) μg/L and (365.91±73.16) μg/L ( t=10.66, P<0.001) there was significant difference between the two groups. There was no significant difference in CRP and ESR between the two groups on the 7th day after operation ( P>0.05). The postoperative hospital stay between the experimental group and the control group was (13.88±2.81) d and (22.78±2.51) d, the difference was statistically significant ( t=16.07, P<0.001). Conclusion:The application of side-to-side jejunostomy combined with jejunal nutrition tube for enteral nutrition in gastric cancer surgery can reduce the occurrence of adverse reactions such as postoperative abdominal pain, abdominal distension, accumulated pneumonia, nausea, vomiting and pleural effusion, reduce the postoperative hospital stay and reduce the postoperative inflammatory reaction to a certain extent.

Objective:To investigate the value of a preoperatively MRI-based deep learning (DL) radiomics machine learning model to distinguish low-grade and high-grade soft tissue sarcomas (STS).Methods:From November 2007 to May 2019, 151 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled as training sets, and 131 patients in the Affiliated Hospital of Shandong First Medical University and the Third Hospital of Hebei Medical University were enrolled as external validation sets. According to the French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) system, 161 patients with FNCLCC grades Ⅰ and Ⅱ were defined as low-grade and 121 patients with grade Ⅲ were defined as high-grade. The hand-crafted radiomic (HCR) and DL radiomic features of the lesions were extracted respectively. Based on HCR features, DL features, and HCR-DL combined features, respectively, three machine-learning models were established by decision tree, logistic regression, and support vector machine (SVM) classifiers. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each machine learning model and choose the best one. The univariate and multivariate logistic regression were used to establish a clinical-imaging factors model based on demographics and MRI findings. The nomogram was established by combining the optimal radiomics model and the clinical-imaging model. The AUC was used to evaluate the performance of each model and the DeLong test was used for comparison of AUC between every two models. The Kaplan-Meier survival curve and log-rank test were used to evaluate the performance of the optimal machine learning model in the risk stratification of progression free survival (PFS) in STS patients.Results:The SVM radiomics model based on HCR-DL combined features had the optimal predicting power with AUC values of 0.931(95%CI 0.889-0.973) in the training set and 0.951 (95%CI 0.904-0.997) in the validation set. The AUC values of the clinical-imaging model were 0.795 (95%CI 0.724-0.867) and 0.615 (95%CI 0.510-0.720), and of the nomogram was 0.875 (95%CI 0.818-0.932) and 0.786 (95%CI 0.701-0.872) in the training and validation sets, respectively. In validation set, the performance of SVM radiomics model was better than those of the nomogram and clinical-imaging models ( Z=3.16, 6.07; P=0.002,<0.001). Using the optimal radiomics model, there was statistically significant in PFS between the high and low risk groups of STS patients (training sets: χ2=43.50, P<0.001; validation sets: χ2=70.50, P<0.001). Conclusion:Preoperative MRI-based DL radiomics machine learning model has accurate prediction performance in differentiating the histopathological grading of STS. The SVM radiomics model based on HCR-DL combined features has the optimal predicting power and was expected to undergo risk stratification of prognosis in STS patients.

Fifty three HIC/AIDS patients with acute appendicitis treated in our hospital from January 2016 to June 2017 were retrospectively analyzed.The anesthesia and surgery were successfully completed in all patients,and there were no serious intraoperative complications.The postoperative complications occurred in 18 cases (34.0 ％),including 13 cases (24.5 ％) of incision infections and 3 cases (5.7 ％) of lung infections,1 case of adhesion obstruction (1.9 ％) and 1 case (1.9 ％) of new opportunistic infections.All patients were clinically cured after treatment and discharged from the hospital without perioperative death.The characteristics of acute appendicitis in HIV/AIDS patients are emergent onset,poor body condition,lower immunity,more comorbities,rapid condition changes,and high frequency of special infections;the patients with lower CD4 count may have higher postoperative infection,the slower recovery and the poorer outcomes.

Objective To explore the regulation and mechanism of Cav1.2 current by KCNE1. Methods Transient transfection was used to transfer Cav1.2 channel plasmids separately or together with KCNE1 plasmids into HEK293 cells. The experiment was divided into 2 groups (15 cells in each group):Cav1.2 group, Cav1.2+KCNE1 group.The whole-cell patch clamp technique was used to record Cav1.2 current and gating dynamics. Results After co-transfection of KCNE1 with Cav1.2, Cav1.2 current decreased significantly. At 0 mV, peak current density of Cav1.2 was reduced from (-14.8±2.5) pA/pF to (-7.5±1.6) pA/pF (n=15, P<0.01). Based on the gate control mechanism, it is found that the regulation of Cav1.2 current by KCNE1 mainly makes the steady-state inactivation curve of the channel shifted to a more negative direction, thus accelerating the inactivation. Meanwhile, the recovery process of the channel after inactivation is slowed down and the recovery time constant was prolonged. Conclusions The KCNE1 subunit can reduce the current density of Cav1.2 by changing the channel inactivation and recovery process.

Objective To observe the effect of KN93, a CaMK Ⅱ inhibitor, on delayed afterdepolarization (DAD) and calcium ion in ventricular myocytes of rabbits with heart failure, and to investigate the effect of CaMK Ⅱ signaling pathway on trigged arrhythmia after heart failure. Methods Thirty male New Zealand White rabbits were randomized(random number) into the sham operated group (sham group), heart failure group (HF group) and heart failure with KN93 group (HF+KN93 group) (n=10 each group). The rabbit heart failure model was established by abdominal aortic constriction combined with aortic valve regurgitation. The ventricular myocytes were isolated by double enzyme digestion. The action potential and the transient inward current (Iti) were recorded by the whole-cell patch-clamp. The intracellular calcium transient was measured by the ion concentration measurement system. The main calcium transporter protein was detected by Western blotting. Data were analyzed by pCLAMP10.2. Statistical analysis was performed using SPSS 17.0. Comparisons among groups were conducted using ANOVA, and SNK-q multiple comparison procedure was utilized for post-hoc analysis.Results (1) After induction of heart failure, DAD and increment of trigger activity (TA) were observedin rabbit ventricular myocytes. Treatment of KN93 with 1.0 μmol/L reduced the events of DAD and TA.(2) After induction of heart failure, Iti densities were increased from -0.12±0.02 pA/pF to -0.95±0.06pA/pF at the polarization potential of -50 mV (n=10, P<0.01). The current densities were reduced to -0.44±0.04 pA/pF after application of 1.0 μmol/L of KN93 (n=10, P<0.01). (3) KN93 led to decrementof intracellular calcium ion concentration and calcium transient amplitude, and acceleration of the decayprocess of calcium transient. (4) KN93 upregulated the expression of pPLN and SERCA2a, increased the uptake of intracellular calcium ion, downregulated the expression of NCX, decreased the Iti, and reduced the occurrence of DAD and TA. Conclusions KN93 can reduce the intracellular calcium ion concentration of the heart failure animal model, and the occurrence of the DAD and TA. CaMK Ⅱ may be a new therapeutic target for arrhythmias in the heart failure.

Objective To observe the effect of allicin on the action potential duration (APD) and L-type calcium current (ICa,L) in the ventricular myocytes of rabbits with heart failure in order to explore the mechanisms of therapeutic effect of allicin on cardiac arrhythmias complicated with heart failure.Methods Forty-five New Zealand White male rabbits were randomly (random number) assigned to 3 groups (n=15 in each group):sham operated group (sham group),heart failure group (HF group),and heart failure treated with allicin group (HF+All group).The rabbit heart failure model was established by abdominal aortic constriction coupled with aortic regurgitation,the ventricular myocytes were obtained by enzyme double digestion,and the whole cell clamp was used to record action potential and calcium current.The action potential duration (APD),Ica,L and gating mechanism were observed during heart failure and allicin administered.Data were processed with pCLAMP version 10.2.Statistical analysis was performed using SPSS 17.0.Comparisons among groups were carried out using ANOVA,and SNK-q was used for multiple comparison as post-hoe.Results (1) Prolonged APD was found during heart failure,APD50 was prolonged from (93.4±4.7) ms in sham group to (115.5±6.2) ms in HF group(P＜0.01).After administration of allicin 30 μmol/L,APD50 was shortened to (105.2±5.5) ms (P＜0.05).(2) The density of ICa.L increased during heart failure,peak current density increased increased from (-8.4±0.6) pA/pF in sham group to (-15.1± 1.1) pA/pF while 0 mV attained at depolarizations (P＜0.01).After administration of allicin 30 μmol/L,the current density reduced to (-10.1+0.8) pA/pF (P＜0.01).The effect of allicin presented in both voltage dependent and consentration dependent manner.(3) According to the gating mechanism study,the main mechanism of lowering the density of ICa,L by allicin after heart failure was the acceleration of the steady inactivation of the channel,and the de-escalation of the recovery kinetic after the inactivation of the channel.Conclusions Allcin can be used to reduce the calcium current of ventricular myocytes in animal heart failure model,it has the potential of clinical use in treating cardiac arrhythmias during heart failure.

Objective To study the medical imaging findings and the pathological features of hepatic inflammatory myofibroblastic tumor (HIMT) using CT,MRI and histopathology.Methods The CT and MRI findings of 31 patients with HIMT which were confirmed by histopathology on surgically resected specimen were analyzed retrospectively.The location,size,shape,edge,density or signal,and contrast enhancement of these tumors were analyzed.Results The tumors were located in the right liver in 26 patients,in the left liver in 5 patients,and under the hepatic capsule in 27 patients.The tumors were solitary in 28 patients and multiple in 3 patients.The maximum diameter of the tumor ranged from 2.1 cm to 12.5 cm.The average diameter was (3.6 ± 1.2) cm.The tumors were round or oval in 21 patients and irregular in 10 patients.19 patients underwent CT examination and all tumors showed low density,with a CT value which ranged from 5 to 35HU.The average value was (27.6 ±5.3) HU.The density of tumors was homogeneous in 6 patients and inhomogeneous in 13 patients,and among these 13 patients,3 were alveolate.Twenty-one patients underwent MRI scan and all showed a low signal on T1WI,12 patients showed an equal signal and 9 patients showed a slightly higher signal on T2WI.In 6 patients the signals were homogeneous and in 15 patients they were inhomogeneous.On CT and MRI enhanced scans the whole tumor was enhanced in 12 patients,the edge was enhanced in 9 patients,the septum was enhanced in 8 patients and no enhancement was observed in 2 patients.Pathological examination under microscopy observed the presence of proliferation of spindle cells,chronic inflammatory cells which included the proliferation of lymphocytes,plasma cells and collagen fiber formation.The spindle cells had the characteristics of fibroblasts and myofibroblast cells.Immunohistochemical examination showed the wave type protein (Vimentin) was positive in 23 patients,the smooth muscle actin (SMA) was positive in 18 patients,the muscle actin (MSA) and the specificity of junction protein (Desmin) were positive in 12 patients,CD68 was positive in 4 patients,and the ALK,S-100 protein,CDll7 and CD35 were all negative.Conclusions The radiological features of CT and MRI plain scan varied.The patterns of contrast enhancement included full tumor filling,marginal enhancement,compartment enhancement,and no enhancement.The enhanced features varied from mild to moderate enhancement in the arterial phase,further enhancement in the portal phase and mild enhancement in the delayed phase.