Chemoresistance to 5-fluorouracil (5-FU) is a significant challenge in treating colorectal cancer (CRC). Novel combined regimens to thwart chemoresistance are therefore urgently needed. Herein, we demonstrated that the combination of Avenanthramide A (AVN A) and 5-FU has significant therapeutic advantages against CRC. Mechanistically, AVN A directly binds to the S198 site of the histone lysine demethylase KDM4C to promote its degradation, which subsequently fosters H3K9me3 occupancy on the MIR17HG promoter to block its transcription and derepress Bim expression. AVN A enhanced the therapeutic efficacy of 5-FU via impairing the KDM4C/MIR17HG/GSK-3β negative feedback loop. Importantly, the clinical correlation of the KDM4C/MIR17HG/Bim signaling axis with 5-FU response was validated in the refractory CRC patients. We provide evidence for the enhanced effectiveness of 5-FU when combined with AVN A in chemoresistant xenografts, CRC organoids, and Apc ^Min/+ mouse model. Additionally, AVN A mitigated the systemic adverse effects of 5-FU. Overall, our findings demonstrate that combinatorial therapy with AVN A and 5-FU represents an appealing opportunity and highlights KDM4C/MIR17HG/GSK-3β negative feedback loop which confers therapeutically exploitable vulnerability to chemo-refractory CRC patients.

Objective:To investigate the availability and safety of a domestic disposable digital flexible cystoscope compared with a reusable Olympus digital flexible cystoscope in cystoscopy and removal of double J stent.Methods:From August 2018 to March 2019, patients were enrolled in this prospective, open, multicenter, randomized, parallel positive controlled clinical trial study, which were from department of Urology in Renmin Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University and the First Affiliated Hospital of Guangzhou Medical University. The experimental group and control group were assigned into a 1∶1 ratio by random table method. Inclusion criteria included age≥18 years and have indications for cystoscopy or removal of double J stent. Exclusion criteria included patients having acute genitourinary tract infection, having tuberculous bladder contracture, bladder capacity less than 50ml, having urethrostenosis, female menstrual period, pregnancy and lactation, having difficulty for lithotomy position, having serious cardio-cerebrovascular disease and liver or kidney dysfunction. A domestic disposable digital flexible cystoscope was adopted in the experimental group, whereas a reusable Olympus digital flexible cystoscope was used in the control group. Acceptability of image was defined as primary availability indicator, while success rate of working and performance score were defined as secondary availability indicators and mean operating time was calculated for cystoscopy only and cystoscopy plus removal of double J stent respectively, yet rate of adverse event as well as rate of equipment defects were sorted as safety indicators.Results:A total of 188 cases which were listed in per protocol set completed the clinical trial study successfully. There were 95 cases in the experimental group and 93 cases in the control group. Acceptability of image was 93.68%(89/95) and 96.77%(90/93) respectively in two groups( P=0.52). Success rate of working was 100.00%(95/95) and 98.92%(92/93) respectively in two groups ( P=0.49). Performance score was 14.41±0.93 and 14.56±0.84 respectively in two groups ( P=0.23). Mean operating time (MOT) only for cystoscopy was (15.3±2.6) min and (15.4±3.3)min respectively in two groups ( P=0.93), while MOT for cystoscopy plus removal of double J stent was (21.0±3.2) min and (21.7±3.9) min respectively in two groups ( P=0.69). Rate of adverse event was 8.42%(8/95) and 9.68%(9/93) respectively in two groups( P=0.76). There was no equipment defects in both groups. Conclusions:There is no statistical difference in acceptability of image, success rate of working, performance score, mean operating time for cystoscopy or removal of double J stent, rate of adverse events and rate of equipment defects. A domestic disposable digital flexible cystoscope has shown non-inferiority in the availability and safety compared with a reusable Olympus digital flexible cystoscope.

Objective To investigate the clinical value of 99Tcm-methoxyisobutylisonitrile (MIBI) double-phase imaging in differential diagnosis of bone lesions in tumor patients,which was indefinite in 99Tcm-methylene diphosphonate (MDP) bone imaging,and evaluate the correlation between 99Tcm-MIBI imaging and chemotherapy efficacy.Methods Fifty-two tumor patients (23 males,29 females,mean age 58 years) with bone isolated lesions(≤3) found by 99Tcm-MDP bone scintigraphy was enrolled from June 2014 to November 2015.Since the results of 99Tcm-MDP imaging were indefinite,99Tcm-MIBI double-phase (10 min and 30 min after injection of 99Tcm-MIBI) SPECT/CT imaging was then performed within 1 week.The final diagnosis was made according to results of more than two imaging modalities (CT,MRI,PET/CT) and/or follow-up (≥6 months).The diagnostic efficacy of 99Tcm-MIBI SPECT/CT imaging was calculated.The clinical dataof chemotherapy were also collected.Patients with bone metastasis were grouped as the treatment response.Retention index (RI) of metastatic lesions was calculated and compared between different groups using two-sample t test.The relationship between RI and chemotherapy efficacy was investigated by Spearman correlation analysis.Results A total of 12 benign lesions and 84 malignant lesions were eventually diagnosed.The sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and Youden index of 99Tcm-MIBI imaging were 96.43％(81/84),83.33％(10/12),97.59％(81/83),76.92％(10/13),and 0.80,respectively.The RI was statistically different between complete remission (CR)+partial remission (PR) group and stable disease (SD) + progressive disease (PD) group:-0.142± 0.036 vs-0.384± 0.067 (t =2.367,P＜0.05).The RI of 99Tcm-MIBI in bone metastases was positively correlated with the chemotherapy efficacy (rs =0.78,P＜0.01).Conclusions 99Tcm-MIBI imaging is helpful in differential diagnosis of bone lesions with indefinite diagnosis by 99Tcm-MDP bone imaging in tumor patients.99Tcm-MIBI RI of bone metastasis may predict the therapeutic response of chemotherapy efficacy.

Objective To analysis the post-dialysis fatigue status of maintenance hemodialysis patients,explore the influencing factors in these patients and propose effective interventions.Methods One hundred and twenty maintenance hemodialysis patients in Department of Nephrology,Second Affiliated Hospital of Nanjing Medical University were enrolled.Clinical data were obtained by questionnaires.Biochemical changes before and post hemodialysis were recorded.The serum concentrations of hemoglobin,albumin,electrolyte,bicarbonate and lactic acid were collected for analysis.Results One hundred and nine(90.8％)effective questionnaires were collected,in which more than half of patients claimed to experience post-dialysis fatigue.Time to recover from hemodialysis(TIRD)was different:the median(interquartile range)time was 2.00(0.00,3.00)hours.In the study,30.3％patients reported no fatigue after hemodialysis.Recovery time in 35.8％patients was more than 30 minutes to 2 hours,22.0％was 3 to 4 hours,11.0％was 5 to 12 hours,0.9％patients took longer time to recover from a dialysis session.According to the recovery time,these patients were divided into three groups.Among the three groups,the ultrafiltration,the serum sodium and lactic acid after dialysis showed significant difference.It was showed by the unconditional logistic regression analysis that ultrafiltration(OR=2.35,95％CI 1.44-3.83),serum sodium(OR=0.75,95％CI 0.65-0.88),lactic acid(OR=3.16,95％CI 1.32-7.55)were associated of TIRD.Conclusions The incidence of post-dialysis fatigue is high.Most of the patients require more rest or sleep immediately after dialysis.The level of lactic acid is a significant influencing factor of the fatigue of patients.TIRD is correlated with the elevation of lactic acid during the dialysis process,and more attention should be paid to postdialysis fatigue.

Objective: To evaluate the safety, feasibility and operational effectiveness of master-slave system controlled Robot-assisted flexible endoscopy 'YunSRobot’ in upper gastrointestinal endoscopy examination in living pigs. Methods: Seven Guangxi BA-MA Mini-pigs underwent upper gastrointestinal endoscopy examination with master-slave system controlled Robot-assisted flexible endoscopy 'YunSRobot’ and Olympus GIF-Q260J gastroendoscope (Japan). The experiment divided into manual operation group and robot operation group. Nine gastroenterologists skilled with endoscopy operation handled the robot once in vitro to familiar with the mechanism and method of robot operation. And then performed manual operation and robot operation four times each. Endoscopy pictures and operation time were recorded. T test and one-way analysis of variance were performed for statistical analysis. Results: Both manual operation and robot operation could successfully finish standard esophagus and stomach endoscopic examination. There were no complications such as hemorrhage, perforation, mistaken insertion into of trachea, injures of pharynx and larynx and inhalation pneumonia. Esophagus, gastric cardia, gastric fundus, gastric body, gastric angle, gastric antrum and gastric pylorus could be clearly observed in both groups. The manual operating time of nine gastroenterologists was (3.67±1.95) minutes, which was shorter than that of robot operating time ((7.60±2.00) minutes), and the difference was statistically significant (t=8.445, P<0.01). The time of first in vitro operation performed by nine gastroenterologist was (13.10±6.32) minutes. The operation times of each case of nine gastrienterologist were (8.49±0.90) minutes, (7.50±1.19) minutes, (7.30±1.33) minutes and (7.12±1.61) minutes. The difference was statistically significant (F=7.901, P<0.01). Operation time gradually shortened and operation proficiency significantly improved. Conclusion Master-slave system controlled Robot-assisted flexible endoscopy 'YunSRobot’ which provides a clear observation of esophagus and stomach is safe in endoscopic examination of living animal.

Increasing prevalence of childhood obesity poses threats to the global health burden. Because this rising prevalence cannot be fully explained by traditional risk factors such as unhealthy diet and physical inactivity, early-life exposure to endocrine disrupting chemicals (EDCs) is recognized as emerging novel risk factors for childhood obesity. EDCs can disrupt the hormone-mediated metabolic pathways, affect children’s growth and mediate the development of childhood obesity. Many organic pollutants are recently classified to be EDCs. In this review, we summarized the epidemiological and laboratory evidence related to EDCs and childhood obesity, and discussed the possible mechanisms underpinning childhood obesity and early-life exposure to non-persistent organic pollutants (phthalates, bisphenol A, triclosan) and persistent organic pollutants (dichlorodiphenyltrichloroethane, polychlorinated biphenyls, polybrominated diphenyl ethers, per- and polyfluoroalkyl substances). Understanding the relationship between EDCs and childhood obesity helps to raise public awareness and formulate public health policy to protect the youth from exposure to the harmful effects of EDCs.
Adolescent ; Diet ; Endocrine Disruptors* ; Global Health ; Halogenated Diphenyl Ethers ; Humans ; Metabolic Networks and Pathways ; Pediatric Obesity* ; Polychlorinated Biphenyls ; Prevalence ; Public Health ; Risk Factors

Objective To evaluate the clinical value of 99Tcm-Tilmanocept(TMC) SPECT/CT for the detection of SLN by comparing with 99Tcm-sulfur colloid(SC) SPECT/CT. Methods From March 2016 to September 2016, a total of 160 patients (age range: 30-70 years), selected from Breast Surgery Department of Shandong Cancer Hospital, underwent SPECT/CT and planar imaging with either 99Tcm-TMC (TMC group, n=76) or 99Tcm-SC (SC group, n=84). The results of SLN SPECT/CT and planar imaging were compared. The positive rate of SLN in SPECT/CT was compared with operative results. One-way analysis of variance, χ2 test, and two-sample t test were used for data analysis. Results The radiochemical purity of 99Tcm-TMC (≥92%) had no significant difference in 4 h(F=0.720, P>0.05). In TMC group, the average number of SLN detected by SPECT/CT imaging was higher than that by planar imaging (1.34±0.64 vs 0.96±034; t=4556, P<005). In SC group, the average number of SLN detected by SPECT/CT imaging was also higher than that by planar imaging (2.57±0.99 vs 1.56±0.87; t=7.010, P<0.05). The positive rates of SLN in TMC and SC groups were 94.7%(72/76)and 96.4%(81/84), showing no significant difference (χ2=0273, P>0.05). The average number of SLN detected by 99Tcm-TMC imaging was significantly lower than that detected by 99Tcm-SC (t=9.115, P<0.05). The intraoperative detection rates of SLN were 100% (76/76 and 84/84) in both groups. The average number of SLN detected during operation in TMC group was significantly lower than that in SC group (1.89±0.86 vs 3.05±1.29; t=6.642, P<0.01). In TMC group, the average number of SLN detected during operation was significantly higher than that detected by SPECT/CT(1.89±086 vs 1.34±0.64; t=4.492, P<0.05). In SC group, the average number of SLN detected during operation was significantly higher than that detected by SPECT/CT(3.05±1.29 vs 2.57±0.99; t=2.740, P<005). Conclusions SPECT/CT is superior to planar imaging for the detection and localization of SLN. 99Tcm-TMC is suitable for SLN imaging and intraoperative detection.

OBJECTIVETo observe the efficacy of fenofibrate for hepatic steatosis in rats after severe burn.

METHODSTwenty-seven male SD rats were divided into sham injury group, burn group, and burn+ fenofibrate group according to the random number table, with 9 rats in each group. Rats in sham injury group were sham injured on the back by immersing in 37 ℃ warm water for 15 s and then remained without other treatment. Rats in burn group and burn+ fenofibrate group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back by immersing in 98 ℃ hot water for 15 s, and then they were intraperitoneally injected with lactated Ringer's solution at post injury hour (PIH) 1. From PIH 24 to post injury day (PID) 8, rats in burn+ fenofibrate group were treated with fenofibrate in the dose of 80 mg·kg(-1)·d(-1), while those in burn group were treated with equivalent volume of saline. (1) Three rats of each group were respectively selected on PID 4, 6, and 8 for the collection of inferior vena caval blood samples. Serum content of total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high density lipoprotein (HDL), and low density lipoprotein (LDL) was determined with fully automatic biochemical analyzer. Body mass of each rat was measured immediately after blood sampling, and then rats were sacrificed to collect liver tissue for weighing wet mass. The ratio of wet mass of liver tissue to body mass (liver index) was calculated. Meanwhile, gross observation of liver was performed. (2) One liver tissue sample was harvested from each rat at each time point to observe histopathologic changes with HE staining. One liver tissue slice of each rat at each time point was collected to evaluate degree of hepatic steatosis, and the number of rats in each group in each grade of hepatic steatosis was recorded. Measurement data were processed with analysis of variance of factorial design and SNK test, and enumeration data were processed with Kruskal-Wallis test and Nemenyi test.

RESULTS(1) The content of TC, TG, FFA, and HDL of rats in burn group on PID 4 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC, TG, and FFA of rats was significantly decreased (with P values below 0.05), while the content of HDL of rats was not obviously changed in burn+ fenofibrate group on PID 4 (P>0.05). There were no obvious differences in the content of LDL of rats among 3 groups on PID 4 (with P values above 0.05). The content of TC, TG, and HDL of rats in burn group on PID 6 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC and TG of rats was significantly decreased (with P values below 0.05), while the content of HDL of rats was significantly increased in burn+ fenofibrate group on PID 6 (P<0.05). There were no obvious differences in the content of FFA and LDL of rats among 3 groups on PID 6 (with P values above 0.05). The content of TC and HDL of rats in burn group on PID 8 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC of rats was significantly decreased (P<0.05), while the content of HDL of rats was not obviously changed in burn+ fenofibrate group on PID 8 (P>0.05). There were no obvious differences in content of TG, FFA, and LDL of rats among 3 groups on PID 8 (with P values above 0.05). (2) The texture of liver tissue of rats in burn+ fenofibrate group at each time point was tender and soft, without oil or fat on the section, which was close to the gross condition of liver of rats in sham injury group. Dark yellow plaque scattered on the surface of liver tissue of rats in burn group at each time point with oil and fat on the section, which was especially obvious on PID 6. There was no obvious difference in liver index of rats among 3 groups on PID 4 (F=1.63, P>0.05). On PID 6 and 8, the liver indexes of rats in sham injury group, burn group, and burn+ fenofibrate group were 0.0416±0.0016, 0.0533±0.0054, and 0.0370±0.0069; 0.0423±0.0034, 0.0624±0.0005, and 0.0444±0.0042 respectively. The liver indexes of rats in burn group on PID 6 and 8 were significantly higher than those in the other two groups (with P values below 0.05). There were no obvious differences in the liver indexes of rats between burn+ fenofibrate group and sham injury group on PID 6 and 8 (with P values above 0.05). (3) The liver tissue structure of rats in sham injury group was normal at each time point. Hepatic steatosis of rats in burn group at each time point appeared microvesicular and disperse, which was especially obvious on PID 6. Mild hepatic steatosis was observed in rats of burn+ fenofibrate group on PID 4, and then the structure of liver tissue gradually recovered to normal level from PID 6 on. The degree of hepatic steatosis of rats in sham injury group was 0 grade. One rat in I grade, 1 rat in II grade, and 7 rats in III grade were observed in hepatic steatosis of rats in burn group. Three rats in 0 grade, 4 rats in I grade, and 2 rats in II grade were observed in hepatic steatosis of rats in burn+ fenofibrate group. The degree of hepatic steatosis of rats in burn group was more severe than that in the other two groups (with χ(2) values respectively 56.25 and 162.44, P values below 0.05). The degree of hepatic steatosis of rats in burn+ fenofibrate group was more severe than that in sham injury group (χ(2)=27.51, P<0.05).

CONCLUSIONSFenofibrate can ameliorate the dyslipidemia of severely burned rat, and it can alleviate the degree of hepatic steatosis in certain degree.

Animals ; Burns ; pathology ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dyslipidemias ; drug therapy ; Fatty Acids ; blood ; Fenofibrate ; pharmacology ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

Objective To observe the effects of pretreatment with dimethyloxalylglycine (DMOG) on the survival of multi-territory perforator flap and the vessels of choke zone (CZ) 2 in rat,and to explore related mechanism.Methods Sixty adult SD rats were divided into group DMOG and normal saline group (NS) according to the random number table,with 30 rats in each group.Perforator flap with three angiosomes was made on the right dorsal side of rat,including deep iliac circumflex artery perforator,intercostal artery perforator,thoracodorsal artery perforator,as well as CZ 1 and CZ 2.Rats in group DMOG were intraperitoneally injected with 2 mL NS containing DMOG (40 mg/kg) 2 days before operation,2 hours before operation,and 2 days after operation.Rats in group NS were intraperitoneally injected with equivalent volume of NS at the same time point.On post operation day (POD) 7,gross observation was conducted,and the survival rate of flap was calculated.On POD 7,the vascularity in CZ 2 and potential zone of flap was observed using angiography.On POD 7,new vessel in CZ 2 of flap was observed with HE staining,and the microvessel density (MVD) was calculated.On POD 7,the expression of vascular endothelial growth factor (VEGF) in CZ 2 of flap was detected by immunohistochemistry and Western blotting (respectively denoted as integral absorbance values and ratio of gray value),and blood flow volume of vessel in CZ 2 of flap was examined by laser Doppler perfusion imager.The sample number of each index was 6 in each group.Data were processed with t test.Results (1) On POD 7,rats in two groups all survived,and the flaps were not infected.In group DMOG,the necrotic area of flaps of rats with dark yellow crust and soft texture was observed approximately at the distal end of skin entry point of thoracodorsal artery perforator.In group NS,the necrotic area of flaps of rats with brownish black crust and hard texture was observed approximately at the distal end of CZ 2.The survival rate of flap of rats in group DMOG was (88 ± 3) ％,which was significantly higher than that in group NS [(82 ± 3) ％,t =3.38,P ＜ 0.01].(2) On POD 7,there were clear vascular structure and many new vessels in CZ 2 of flaps of rats in group DMOG,with intact vascular structure in potential zone.On POD 7,there were unclear vascular structure and few new vessels in CZ 2 of flaps of rats in group NS,with disorder vascular structure in potential zone.(3) On POD 7,MVD in CZ 2 of flaps in rats of group DMOG was (29.2 ± 2.2)/mm2,which was significantly higher than that of group NS [(20.3 ± 3.6)/mm2,t =5.10,P ＜0.01].(4) On POD 7,the expressions of VEGF in CZ2 of flaps in rats of group DMOG detected by immunohistochemistry and Western blotting were 5 060 ± 432 and 0.48 ± 0.04 respectively,which were significantly higher than those of group NS (2 811 ± 382 and 0.26 ± 0.06,with t values respectively 9.54 and 5.67,P values below 0.01).(5) On POD 7,blood flow volume of vessel in CZ 2 of flaps in rats of group DMOG was (58 ±4) perfusion units (PU),which was significantly more than that of group NS [(46 ± 4) PU,t =5.20,P ＜ 0.01].Conclusions DMOG can increase the survival rate of multi-territory perforator flap through promoting angiogenesis in CZ 2 of flap on the back of rat and improving blood supply of flap.

Objective To prospectively investigate the optimal setting for sentinel lymph node biopsy (SLNB) in patients with breast cancer by comparing the effects of different preparation methods and injection sites of 99Tcm-SC in sentinel lymph node (SLN) mapping and detection.Methods Two batches of 99Tcm-SC were prepared by boiling for 3 min (radiotracer 1) and 5 min (radiotracer 2),respectively.Radioactive chemical purity (RCP) and size of colloid particles were measured at 10 min,1 h,2 h and 4 h after the preparation.One hundred and forty-seven patients with breast cancer were involved and randomly divided into 3 groups.Group A consisted of 40 patients with periareolar injection of radiotracer 1,group B of 40 patients with periareolar injection of radiotracer 2,and group C of 67 patients with peritumoral injection of radiotracer 2.Lymphatic mapping was performed for all patients using SPECT/CT preoperatively and blue dye was subdermally injected over the tumor.The detection rate of the axillary and internal mammary SLN was recorded.One-way analysis of variance,independent two-sample t and x2 tests were used to analyze the data.Results There was no significant difference of RCP between the two radiotracers at 10 min,1 h,2 h and 4 h after preparation (t =-0.267,-0.794,0.826 and-0.977,all P＞0.05).Compared with radiotracer 1,the percentage of particles smaller than 100 nm in radiotracer 2 reduced significantly ((73.72±2.36) ％ vs (65.25±3.56)％,t=6.436,P＜0.05) and the mean effective particle size was significantly larger ((45.27±6.42) nm vs (75.59t7.04) nm,t=7.315,P＜0.05).In groups A,B and C,the detection rate of the internal mammary SLN was 70.0％ (28/40),47.5％ (19/40) and 17.9％ (12/67),respectively,with significant difference (x2=29.525,P＜0.05).In groups A,B and C,the detection rate of the axillary SLN was 100％ (40/40),95.0％ (38/40) and 97.0％ (65/67),respectively,without significant difference (x2 =2.686,P＞ 0.05).Conclusion For SLNB of patients with breast cancer,the axillary and internal mammary SLN could be better detected by SPECT/CT lymphatic mapping using radiotracer prepared with a shorter boiling time,via periareolar injection,and combined with subdermal injection of blue dye.