1.Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Shi QIU ; Yaqi QIU ; Linghui DENG ; Ling NIE ; Liming GE ; Xiaonan ZHENG ; Di JIN ; Kun JIN ; Xianghong ZHOU ; Xingyang SU ; Boyu CAI ; Jiakun LI ; Xiang TU ; Lina GONG ; Liangren LIU ; Zhenhua LIU ; Yige BAO ; Jianzhong AI ; Tianhai LIN ; Lu YANG ; Qiang WEI
Chinese Medical Journal 2024;137(2):209-221
Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
2.Research progress on obesity-related genes
Lin LIU ; Ting XU ; Hongwei ZHANG ; Jianzhong DI
International Journal of Surgery 2021;48(11):778-782
Obesity is an independent risk factor for many chronic diseases, which seriously affects the quality of life and physical and mental health of patients, and is a serious public health problem facing society. Obesity research is the focus and difficulty of current medical research. At present, laparoscopic sleeve gastrectomy and gastric bypass surgery have become important ways to treat obesity, but the specific mechanism is still unclear. In recent years, research on obesity-related genes has made certain progress. The link between surgery and obesity gene expression is gradually being discovered. Different gene functions such as energy intake and consumption and fat storage by fat cells have also derived different treatment methods. This article will summarize the research on obesity genes.
3.Research progress on pregnancy risks and timing following bariatric surgery
Ting XU ; Chen WANG ; Hongwei ZHANG ; Xiaodong HAN ; Weijie LIU ; Pin ZHANG ; Jianzhong DI
International Journal of Surgery 2020;47(4):265-268
The number of women of childbearing age having overweight or obesity problems keeps increasing globally. Besides diabetes, hypertension and other chronic conditions, these women may develop metabolic disorders of sex hormones, manifested by irregular menstruation, infertility and obstetric complications. Bariatric surgery offers prominent weight loss and improves obesity-related conditions. Women patients also benefit from elevated chances of pregnancy postoperatively. However, the timing of pregnancy for obese women after surgery has impact on the effects of weight loss surgery, pregnancy complications, delivery outcomes and long-term prospects of mother and child. This article reviews the clinical studies on the timing of pregnancies after bariatric surgery, weight loss results, as well as risks and outcomes.
4.Clinical research on osteoporosis and fracture risks in plateau areas in China
Wenxin LIU ; Ting XU ; Chen WANG ; Jianzhong DI
Chinese Journal of Orthopaedic Trauma 2019;21(6):545-548
Osteoporosis is a chronic disease influenced by multiple factors.The fractures associated with osteoporosis are known as osteoporotic fractures.The factors associated with osteoporosis and fracture include oxygen concentration,sunshine,body mass,gender,age,trauma,dietary habits,tobacco and alcohol use,medical history and inheritance.Factors such as oxygen concentration,topography and dietary habits play a more important role in the western plateau areas in China than in the plain areas.The present study reviews the clinical research on the osteoporosis and fracture risks in the plateau areas in China and proposes prevention and treatment measurements for the risk factors to reduce the incidences of osteoporosis and fracture in the plateau areas.
5.Needle-stick injuries among health care workers and protective strategies in a hospital
Zhen ZOU ; Yumei YANG ; Yunxia WANG ; Jianzhong DI
Chinese Journal of Infection Control 2017;16(6):548-550
Objective To investigate the condition and causes of needle-stick injuries among health care workers(HCWs), and explore effective strategies for preventing needle-stick injuries.Methods Needle-stick injuries recorded by healthcare-associated infection management department in a hospital between January 2013 and December 2015 were surveyed retrospectively.Results 164 HCWs suffered needle-stick injuries, including 71 (43.29%) doctors, 81 (49.39%) nurses, and 12 (7.32%) other HCWs.The number of injuries in 2013, 2014, and 2015 were 47(28.66%), 54(32.93%),and 63(38.41%)respectively.152(92.68%), 9(5.49%),and 3(1.83%)injuries were caused by contaminated medical instruments, uncertain-contaminated medical instruments, and non-contaminated medical instruments.Among 164 cases of needle-stick injuries, 67(40.85%) occurred in operating rooms, 141 (85.98%) were finger injuries;the main causes of needle stick injuries were carelessness, busy work and nonstandard manipulation(n=115, 70.12%), most doctors suffered needle stick injuries due to the lack of experience (52.11%), most nurses suffered needle stick injuries due to carelessness, busy work and nonstandard manipulation(93.83%).Conclusion Needle stick injuries among HCWs increased year by year, strategies should be implemented to reduce the occurrence of needle injuries, including strengthening occupational protection consciousness among HCWs, strengthening construction of healthcare-associated infection management system, and improving medical environment.
6.Efficacy and its related factors of phenobarbital treatment for epilepsy management in rural China
Xiaowei WANG ; Xiaojuan RU ; Jianzhong WU ; Zhen HONG ; Di LI ; Shichuo LI ; Wenzhi WANG
Chinese Journal of General Practitioners 2016;15(9):687-692
Objective To analyze efficacy and its influencing factors of phenobarbital treatment for epilepsy management in rural China.Methods Total 3 315 patients with convulsive epilepsy from rural areas of 24 counties were enrolled in this joint epilepsy management program.All patients received phenobarbital monotherapy for 1 year during November 2011 to November 2013.The efficacy and potential influencing factors including sex,age,duration of epilepsy,number of seizures in the 12 months before management(≥2),previous treatment,daily dose of phenobarbital,taking other antiepileptic drugs and compliance of patients were studied with multivariate analysis.Results Among 3 315 patients,38.9% were seizure-free during the entire management period.The rates of seizure-free in 15 to 39 y age group (35.2%,495/1 405)and in patients receiving irregular treatment previously (34.6%,625/1 808)were lower.The rates of seizure-free were higher in patients taking phenobarbital 60-90 mg everyday (49.4%,988/2 000) and those with good compliance(42.3%,1 160/2 744).Patients taking other antiepileptic drugs in 12 months had lower seizure-free rate (31.0%,45/145).Univariate analysis showed that gender of patients was not related to seizure-free rate (P > 0.1).Multivariate analysis showed that the longer duration of epilepsy(OR =0.015,95% CI:1.008-1.021,P < 0.001),more seizures in the 12 months (OR =0.005,95% CI:1.002-1.007,P =0.002) and the irregular treatment before management were the risk factors for low seizure-free rate (P < 0.05).Patients received formal treatment or untreated had a lower risk of seizure compare with the irregular treatment (OR =0.737,95% CI:0.611-0.889,P =0.001;OR =0.566,95% CI:0.469-0.683,P <0.001).Patients with good compliance and with a daily dose of 60-89 mg phenobarbital(OR =0.107,95% CI:0.013-0.905,P =0.040) were associated with high seizurefree rate;in contrast the poor compliance was a risk factor for not being seizure-free(OR =2.038,95% CI:1.634-2.541,P < 0.001).Conclusion Regular medication of phenobarbital with good compliance is effective for convulsive epilepsy management in rural China.
7.High Performance Liquid Chromatogram-Mass Spectrometry for Helicobacter pylori Infection-associated Differentially Expressed Proteins in Urine with Relative Molecular Mass More than 10 kDa
Huifang ZHANG ; Fanliang MENG ; Lihua HE ; Jianzhong ZHANG ; Di XIAO
Chinese Journal of Gastroenterology 2016;21(3):144-150
Background:Helicobacter pylori(Hp)is an important pathogen for peptic ulcer and gastric cancer,and is reportedly associated with a variety of extragastrointestinal diseases. However,there is no body fluid detection technique for Hp infection in clinical practice. Aims:To identify Hp infection-associated differentially expressed proteins in urine with relative molecular mass more than 10 kDa and provide potential biomarkers for diagnosis of Hp infection through body fluid detection. Methods:Midstream urine was collected from volunteers in the morning,and 13 C-urea breath test was performed to determine Hp infection. Each of 15 Hp-negative and 15 Hp-positive urine samples were mixed respectively for protein extraction. Spectra data were acquired by high performance liquid chromatogram-mass spectrometry,and label-free technology was used for relative quantitative analysis. The other 26 urine samples(15 Hp-negative and 11 Hp-positive) were used for validation by full scan. IPA software was employed for bioinformatics analysis. Results:A total of 475 urinary proteins were detected by label-free quantitative analysis and 42 differentially expressed proteins were identified. Finally,11 significantly up-regulated differentially expressed proteins were confirmed by external scanning validation. Bioinformatics analysis revealed the molecular functions,biological pathways,and related diseases of these differentially expressed proteins. Conclusions:These 11 differentially expressed proteins more than 10 kDa identified in urine might be potential biomarkers for diagnosis of Hp infection and provide molecular evidence for the correlation of Hp infection with extragastrointestinal diseases.
8.Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on morbidly obesity
Qinggui REN ; Hongwei ZHANG ; Weifeng DONG ; Weijie LIU ; Xiaodong HAN ; Junfeng HAN ; Pin ZHANG ; Jianzhong DI
Chinese Journal of Endocrine Surgery 2016;10(6):474-477
Objective To evaluate the effects of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy on weight control in morbidly obese patients.Methods 48 patients with morbidly obesity underwent obese surgery (laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) from Dec.2013 to Dec.2015,and 1-year follow-up study.The general situation of obesity and biochemical indicators were compared and analyzed.Results There were 20 cases in gastric bypass group and 28 cases in sleeve gastrectomy group.The excess weight loss percentage(%EWL)was 73±0.04 in gastric bypass group and 59±0.05 in sleeve gastrectomy group(P=-0.03).There was no statistical difference in weight change between the two groups.Low density lipoprotein cholesterol (LDL) level in gastric bypass group was significantly lower than that in sleeve gastrectomy group at 1 year after surgery (2.42±0.16 vs 3.29±0.20,P=0.006),while folic acid level was significantly higher than that in sleeve gastrectomy group(15.58±1.99 vs 7.59±1.59,P=0.022).Conclusions The one-year follow up shows there is no significant difference in the efficacy of weight control between the two groups.Gastric bypass group may be superior to gastrectomy group in nutrition indexes.However,it is just a short-term postoperative efficacy in morbidly obese patients,long-term weight control effects and obesity related diseases control need to be further explored.
9.The clinical analysis of mild hypothermia therapy for severe traumatic brain injury in elderly patients
Hongyu WANG ; Di ZHAO ; Dong LIU ; Jianzhong CUI ; Hongmei ZHANG ; Jun HONG
Chinese Journal of Behavioral Medicine and Brain Science 2016;25(4):350-353
Objective To investigate the clinical therapeutic effect of mild hypothermia in elderly patients with severe traumatic brain injury.Methods 72 cases of elderly patients with severe traumatic brain injury(GCS ≤ 8) were divided into mild hypothermia therapy group(36 patients)and control group(36 patients) according to the random number table method.Mild hypothermia therapy group received mild hypothermia treatment while control group received normal treatment.The clinical prognosis was analyzed between the two groups.Results After 24h treatment,both mild hypothermia therapy group and control group intracranial pressure began to rise.But the intracranial pressure of the mild hypothermia therapy group(24 h:(13.0±4.5)mmHg,3 d:(16.6±4.0) mmHg,5 d:(19.9±3.9) mmHg,1 mmHg=0.133 kPa) were significantly lower than those of the control group (24 h:(16.6± 3.8) mmHg,3 d:(20.4±4.8) mmHg;5 d:(24.1 ± 6.2) mmHg),and the difference was statistically significant (t=2.225,2.260,2.192,P=0.035,0.033,0.039).The rate of good recovery to the control group and the mild hypothermia therapy group were 22.22% and 47.22% respectively while the mortality were 30.56% and 13.89% respectively,and the differences were statistically significant (x2 =4.936,5.675,P=0.047,0.035).Conclusion Mild hypothermia treatment can inhibit the increase of intracranial pressure and reduce disability rate and mortality in elderly patients with severe traumatic brain injury,which can increase the survival rate and improve the long-term prognosis.
10.Incidence of cholelithiasis after laparoscopic Roux-en-Y gastric bypass for the treatment of type 2 diabetes mellitus with obesity
Hongwei ZHANG ; Jianzhong DI ; Haoyong YU ; Xiaodong HAN ; Weijie LIU ; Pin ZHANG
Chinese Journal of Digestive Surgery 2015;14(7):555-559
Objective To investigate the incidence of cholelithiasis after laparoscopic Roux-en-Y gastric bypass(LRYGB) for treatment of type 2 diabetes mellitus with obesity.Methods The clinical data of 89 obese patients with type 2 diabetes mellitus who underwent LRYGB at the Sixth People's Hospital Affiliated to Shanghai Jiaotong University from March 2011 to March 2013 were retrospectively analyzed.Sixty-six patients without postoperative gallstone and sludge were divided into the nornal group and 23 with postoperative gallstone or sludge into the gallstone group.The waistline,hipline,body weight,body mass index (BMI),excess weight loss (EWL),fasting blood glucose,postprandial 2-hour blood glucose,glycosylated hemoglobin (HbAlc),homeostasis model assessment-insulin resistance (HOMA-IR),total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-c),low-density lipoprotein cholesterol (LDL-c),serum total bile acid at postoperative month 6,12,24 were analyzed.The patients were followed up by inpatient,outpatient examination and telephone interview till April 2015.Measurement data with normal distribution were presented as x ± s,comparison between groups and repeated measures data were analyzed using the t test and repeated measures ANOVA,respectively.Count data were analyzed by the chi-square test.Results All the 89 patients underwent successful LRYGB and were fol lowed up for 31 months (range,24-48 months).The EWL,HbAlc and serum total bile acid at postoperativemonth 6,12,24 were 113%±43%,117%±64%,119%±84% and 6.1%±0.8%,6.2%± 1.1%,6.4%± 1.0% and (4.6 ± 3.8) μmol/L,(4.5 ± 3.6) μmol/L,(4.6 ± 3.8) μmol/L in the normal group and 157 % ± 96%,152%±102%,151%±93% and 5.9%±0.8%,5.8%±0.6%,5.9%±0.8% and (23.9 ±9.0) μmol/L,(11.8 ± 7.3) μmol/L,(10.5 ± 9.6) μmol/L in the gallstone group,respectively,showing significant differences in changing trend between the 2 groups (F =6.896,5.226,5.351,P < 0.05).There were significant differences in the EWL at postoperative month 6,12,24 between the 2 groups (t =2.814,2.628,2.099,P < 0.05).There were significant differences in the HbAlc at postoperative month 12 and serum total bile acid at postoperative month 6,24 between the 2 groups (t =2.018,-1.378,-1.990,P < 0.05).Conclusion There is incidence risk of cholelithiasis after LRYGB in obese patients with type 2 diabetes mellitus.The rapid decreasing of weight is associated with cholelithiasis in which patients have higher level of serum bile acid.

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