1.Changes in FOXO1 expression in β-cells during the progression of type 2 diabetes mellitus and aging
Rui LIANG ; Tengli LIU ; Jiaqi ZOU ; Boya ZHANG ; Shusen WANG ; Na LIU
Chinese Journal of Endocrinology and Metabolism 2024;40(5):414-419
Objective:To investigate the changes of β-cell dedifferentiation in type 2 diabetes mellitus(T2DM) and aging subjects.Methods:Using pancreatic samples from 12 prediabetic individuals, 21 type 2 diabetic patients, and 27 control, the level of β-cell dedifferentiation was assessed by immunofluorescence staining for FOXO1 and insulin expression. Correlation analyses were performed between β-cell dedifferentiation levels and hemoglobin A 1C(HbA 1C) level in 60 human pancreatic samples. Correlation analyses were performed between β-cell dedifferentiation levels and age in non-diabetic and T2DM. Results:FOXO1 was mainly expressed in the cytoplasm of human islet β-cells. The proportion of FOXO1 -INS + /INS + cells in T2DM significantly increased compared with control and pre-diabetes, and positively correlated with HbA 1C level( r=0.623, P<0.001). The proportion of FOXO1 -INS + /INS + cells in the young group of T2DM was significantly higher than that in the non-diabetic young and elderly groups, and further significantly increased in elderly group. In T2DM, the proportion of FOXO1 -INS + /INS + cells was positively correlated with age( r=-0.53, P<0.05). Conclusion:Hyperglycemia and aging lead to an increased level of β-cell dedifferentiation in T2DM.
2.Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-Arm, Prospective Study
Kuikui JIANG ; Ruoxi HONG ; Wen XIA ; Qianyi LU ; Liang LI ; Jianhao HUANG ; Yanxia SHI ; Zhongyu YUAN ; Qiufan ZHENG ; Xin AN ; Cong XUE ; Jiajia HUANG ; Xiwen BI ; Meiting CHEN ; Jingmin ZHANG ; Fei XU ; Shusen WANG
Cancer Research and Treatment 2024;56(2):513-521
Purpose:
This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice.
Materials and Methods:
This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety.
Results:
A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%).
Conclusion
Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.
3.JNK inhibitor SP600125 inhibits interleukin-1β induced pyroptosis in βTC-6 cells
Wenmiao MA ; Tengli LIU ; Rui LIANG ; Na LIU ; Le WANG ; Shusen WANG ; Rongxiu ZHENG
Chinese Journal of Endocrinology and Metabolism 2023;39(5):430-434
Objective:To investigate whether interleukin(IL)-1β is involved in pyroptosis which leads to mouse islet β cell line βTC-6 cell damage, and to explore the role of JNK inhibitor SP600125 in inhibiting IL-1β induced βTC-6 cell pyroptosis.Methods:βTC-6 cell line and mouse islets were incubated with IL-1β for 48 h or intervened with both JNK inhibitor SP600125 and IL-1R antagonist IL-1Ra, then GSDMD expression and β cell pyroptosis morphology were detected by immunofluorescence staining of GSDMD and DAPI. The expression levels of Gsdmd, IL-1β and IL-18 mRNAs were detected by real time fluorescence PCR, and apoptosis was examined by Annexin-V/7-AAD staining combined with flow cytometry.Results:βTC-6 cell pyroptotic body was significantly increased in the IL-1β treated group compared with the control group, and the expressions of pyroptosis related genes Gsdmd, IL-1β, and IL-18 mRNA were significantly higher( P<0.05), and apoptosis was increased, suggesting that IL-1β effectively induced the βTC-6 cell pyroptosis, IL-1Ra prevented IL-1β induced βTC-6 cell pyroptosis. In the presence of JNK inhibitor SP600125, IL-1β treatment failed to induce the expressions of Gsdmd and IL-18 mRNA, markers of pyroptosis, and reduced the rate of apoptosis, indicating that SP600125 suppressed IL-1β induced βTC-6 cell pyroptosis. Conclusion:Pyroptosis is one of the mechanisms of βTC-6 cell impairment caused by IL-1β, and SP600125, a JNK inhibitor, can block the IL-1β induced pyroptosis pathway and has a potential role in inhibiting βTC-6 cell pyroptosis.
4.ALDH1A3 + INS + cells in non-diabetic subjects and risk for type 2 diabetes: Analysis of cross-sectional data
Tengli LIU ; Rui LIANG ; Peng SUN ; Le WANG ; Na LIU ; Jiaqi ZOU ; Yaojuan LIU ; Xuejie DING ; Shusen WANG
Chinese Journal of Endocrinology and Metabolism 2022;38(3):219-224
Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.
5.Chinese consensus on surgical treatment of traumatic rib fractures (2021)
Lingwen KONG ; Guangbin HUANG ; Yunfeng YI ; Dingyuan DU ; Baoguo JIANG ; Jinmou GAO ; Lianyang ZHANG ; Jianxin JIANG ; Xiangjun BAI ; Tianbing WANG ; Xingji ZHAO ; Xingbo DANG ; Zhanfei LI ; Feng XU ; Zhongmin LIU ; Ruwen WANG ; Yingbin XIAO ; Qingchen WU ; Chun WU ; Liming CHENG ; Bin YU ; Shusen CUI ; Jinglan WU ; Gongliang DU ; Jin DENG ; Ping HU ; Jun YANG ; Xiaofeng YANG ; Jun ZENG ; Haidong WANG ; Jigang DAI ; Yong FU ; Lijun HOU ; Guiyou LIANG ; Yidan LIN ; Qunyou TAN ; Yan SHEN ; Peiyang HU ; Ning TAO ; Cheng WANG ; Dali WANG ; Xu WU ; Yongfu ZHONG ; Anyong YU ; Dongbo ZHU ; Renju XIAO ; Biao SHAO
Chinese Journal of Trauma 2021;37(10):865-875
Traumatic rib fractures are the most common injury in thoracic trauma. Previously,the patients with traumatic rib fractures were mostly treated non-surgically,of which 50%,especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities,being unable to retain a full-time job. In the past two decades,thanks to the development of internal fixation material technology,the surgical treatment of rib fractures has achieved good outcomes. However,there are still some problems in clinical treatment,including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans,and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore,the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association,in conjunction with national multidisciplinary experts,formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures(2021)following the principle of evidence-based medicine,scientific nature and practicality. This expert consensus puts forward some clear,applicable,and graded recommendations from aspects of preoperative imaging evaluation,surgical indications,timing of surgery,surgical methods,rib fracture sites for surgical fixation,internal fixation methods and material selections,treatment of combined injuries in rib fractures,in order to provide references for surgical treatment of traumatic rib fractures.
6.Adipose Tissue-Derived Stem Cells from Type 2 Diabetics Reveal Conservative Alterations in Multidimensional Characteristics
Le WANG ; Leisheng ZHANG ; Xue LIANG ; Jiaqi ZOU ; Na LIU ; Tengli LIU ; Guanqiao WANG ; Xuejie DING ; Yaojuan LIU ; Boya ZHANG ; Rui LIANG ; Shusen WANG
International Journal of Stem Cells 2020;13(2):268-278
Background and Objectives:
Adipose tissue-derived mesenchymal stem cells (ASCs) are recognized as an advantaged source for the prevention and treatment of diverse diseases including type 2 diabetes mellitus (T2DM). However, alterations in characteristics of ASCs from the aforementioned T2DM patients are still obscure, which also hinder the rigorous and systematic illumination of progression and pathogenesis.
Methods:
and Results: In this study, we originally isolated peripancreatic adipose tissue-derived mesenchymal stem cells from both human type 2 diabetic and non-diabetic donors (T2DM-ASCs, ND-ASCs) with the parental consent, respectively. We noticed that T2DM-ASCs exhibited indistinguishable immunophenotype, cell vitality, chondrogenic differentiation and stemness as ND-ASCs. Simultaneously, there’s merely alterations in migration and immunoregulatory capacities in T2DM-ASCs. However, differing from ND-ASCs, T2DM-ASCs exhibited deficiency in adipogenic and osteogenic differentiation, and in particular, the delayed cell cycle and different cytokine expression spectrum.
Conclusions
The conservative alterations of T2DM-ASCs in multifaceted characteristics indicated the possibility of autologous application of ASCs for cell-based T2DM treatment in the future.
7.Characteristics of micro-spatial structure of artifical nerve bridging substance for repairing nervous segmental defect
Wei LIANG ; Shuhua GE ; Zhuojing LUO ; Mingquan LI ; Shusen WANG
Chinese Journal of Tissue Engineering Research 2007;11(9):1776-1778
BACKGROUND: There is no any mature and complete system to repair nerve tissue after segmental injury due to particularity of nerve tissue regeneration. Using tissue-engineering technique to solve this problem is difficult and challenged.OBJECTIVE: To research an artificial nerve bridging substance in application of repairing nerve injury on clinic and obverse its microcosmic spatial structure at the same time.DESIGN: Open experiment.SETTING: Orthopaedic Research Institute, Xijing Hospital of the Fourth Military Medical University of Chinese PLA.MATERTALS: The experiment was carried out in the Orthopaedic Research Institute, Xijing Hospital of the Fourth Military Medical University of Chinese PLA from November 2001 to January 2003. CollagenⅠ, collagen Ⅳ and gelatin were provided by Sigma-aldrich Company, USA.METHODS: Establishment of bridging substance: Collagen Ⅰ (65.53%) and collagen Ⅳ (32.77%) were added into 0.05 mol/L acetic acid solution, respectively; and then, two suspensions were mixed together and stirred at 4℃. The suspension of collagen and heparin sulfate was pumped, held still and poured into silica gel tube with bore of 3 mm.Continuously, two ends of tube were enclosed and suffered from cold drench and mold at five various speeds. General observation was done. Composites were intercepted cross section, vertical section and 45° section for observation by optic microscope at different speeds of 10×10-5 m/s, 5×10-5 m/s, 2.5×10-5 m/s, 1.0×10-5 m/s and 1.0×10-6 m/s; meanwhile, interior structure of microtubule was observed with scanning electron microscope. Interior diameter of microtubule was calculated as the following formula: actual aperture = (magnification × area of microtubule) ÷ (length of guage × perimeter of aperture).MAIN OUTCOME MEASURES: ① General observation; ② observation with microscope; ③ observation with scanning electron microscope and interior diameter of microtubule.RESULTS: ① General observation: Models were regular cylinders and had symmetrical features. Flexility was wonderful,texture was well-proportioned, and elasticity was strong. ② Results of optic microscope: Structure of external surface was completely blocking without any poricidal dehiscence. Surface was smooth and had good continuity. ③ Results of electron microscope: External surface shaped like terrace tile; asides, interior structure of microtubule was average and its courser was coincident and parallel to each other. Microtubules with longitudinal courser were independence on each other. The structure was blocking and did not connect to each other. This was as the same as courser of nerve fibrous bands of organis. Cross section of interior microtubule was general round and regular, and the diameter was average. Interior microtubule had groat continuity without breaks or transection. Trabeculae of microtubule also had groat continuity,and its surface was smooth. Interior diameter of microtubule ranged from 197.3 μm to 258.8 μm.CONCLUSION: Nerve bridging substance is made of collagen and gelatin which are characterized by groat compatibility and degradation after mixture, lysis and cold drench, It has singly longitudinal microtubule and microstructure of high imitation by normal nerves, so nerve bridging substance can be used in basic researches and repair nerve injury on clinic.
8.RFID Information Management Technology Applying in CSSD
Huasheng WANG ; Ran XU ; Shusen LIANG ; Wei XU
Chinese Journal of Nosocomiology 2006;0(06):-
OBJECTIVE To build up an integrated,flexible,real-time backward management system for recycling medical appliance.METHODS The radiofrequency identification technique(RFID) information management technology was adopted.RESULTS Exertion of RFID information management technology in Central Sterile Supply Department(CSSD) not only promoted its work more effectively,correctly and feasibly,but also guaranteed the quality of recycling medical appliance.CONCLUSIONS The RFID information management technology applying in CSSD,could control the whole process of managing recycling medical appliance backward completely,and gain the legal witness and humanity management.
9.Quantum of Bacteria in Air of Cleaning Section of Disinfecting Supply Division: A Surveillance
Huasheng WANG ; Shusen LIANG ; Xueying SUN
Chinese Journal of Nosocomiology 2006;0(02):-
OBJECTIVE To effectively control the quantum of bacteria existing in the air of the cleaning section in the disinfecting supply division. METHODS The standards and methods set in the Hospital Disinfecting Sanitation Standard(GB15982-1995) were used. RESULTS Scientific,effective and strict control measures should be implemented to make the quantum of bacteria existing in the air to meet the Environment Standard Type Ⅱ. CONCLUSIONS This article provides the credible data for boosting the pureness of the air of the cleaning section of disinfecting supply division.
10.Effect of Quickread-bioindicator: An Observation
Shusen LIANG ; Huasheng WANG ; Ran XU
Chinese Journal of Nosocomiology 2006;0(06):-
OBJECTIVE To observe the effect of the quickread bioindicator. METHODS According to the GB15981-1995 The Measures and the Standards of the Assessment of Disinfection and Sterilization,to control conventionally the(7 high-pressure) steam sterilization cabinets by the quickread-bioindicators. RESULTS Using the effective control method shortened the waiting time by 45 hours,and in-time provided the qualified disinfected supply. CONCLUSIONS The effect of using the quickread-bioindicator resolves the problem of delay of the control result.This is an ideal,scientific,and practical method for effective control of the high pressure steam sterilization.

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