1.Progress on the mechanisms of antifibrotic effects of PPARγ
Yunan SUN ; Qiongyu DUAN ; Rong WU
Practical Oncology Journal 2015;(1):73-77
External beam radiotherapy is a major treatment in the management of cancer .However radia-tion induced pulmonary fibrosis is common .It not only leads to quality -of-life issues in survivors and compro-mise treatment ,but also may even be lethal in outcome .Transforming growth factor β( TGF-β) seems to be a key mediator of fibrosis .TGF-βpromotes the differentiation of fibroblasts into myofibroblasts while the differentiation and activation of fibroblasts and myofibroblastsmay produce the components of scar tissue, which is one of the key pathogenic processes in lung fibrosis .Peroxisome proliferator activated receptors ( PPARs ) are ligand activated transcription factors that belong to the nuclear hormone receptor superfamily .PPARγis also a key regulator of fi-broblast differentiation .Many studies have shown that both natural ligand and synthetic ligand of PPARγcan sup-press fibrosis by interfering with TGF -βsignaling and some other approaches .The antifibrotic effects of PPARγhave been reported to be involved in both PPARγdependent and PPARγindependent mechanisms .PPARγago-nists may have potential for the therapy of radiation induced pulmonary fibrosis .
3.Effects of Electroacupuncture on Learning and Memory Ability and RhoA expression in Rats after Cerebral Ischemic-reperfusion
Yunan WU ; Yun ZHANG ; Ruhui LIN ; Lidian CHEN ; Jing TAO
Chinese Journal of Rehabilitation Theory and Practice 2015;(1):17-21
Objective To explore the effects of electroacupuncture at Shenting (DU24) and Baihui (DU20) on learning and memory ability in the cerebral ischemia-reperfusion rats and its possible mechanism. Methods 45 male Sprague-Dawley rats were randomly divided into sham group (n=15), ischemia group (n=15) and electroacupuncture group (n=15). The latter 2 groups were modeled as focal cerebral ischemia-reperfusion injury, and the electroacupuncture group received electroacupuncture at Shenting (DU24) and Baihui (DU20) for 7 days. They were tested with Morris Water Maze, observed with Nissl's staining. The protein expression of RhoA was detected with Western blotting. Results The learning and memory ability improved in the electroacupuncture group (P<0.05), the injury of the neurons reduced (P<0.05) and the expression of RhoA in hippocampus decreased compared with the ischemia group (P<0.05). Conclusion Electroacupuncture could ameliorate the learning and memory ability in ischemia- reperfusion rats, which may relate with the inhibition of the expression of RhoA in hippocampus.
4.Effects of Electroacupuncture at Baihui (DU20) on Learning and Memory and Expression of Brain-derived Neu-rotrophic Factor in APP/PS1 Double-transgenic Mice
Jixiang CHEN ; Yunan WU ; Yaxuan ZHENG ; Peiyuan ZHUO ; Yingzheng ZHANG ; Lidian CHEN
Chinese Journal of Rehabilitation Theory and Practice 2015;21(6):642-647
Objective To explore the effects of electroacupuncture at Baihui (DU20) acupoint on learning and memory and its possible mechanism through the expression of brain-derived neurotrophic factor (BDNF) in APP/PS1 double-transgenic mice. Methods 30 female APP/PS1 double transgenic mice were randomly divided into model group, DU20 group and non-acupoint group, and 10 wild type mice con-sisted of wild group. DU20 group received electroacupuncture at Baihui and the non-acupoint group received electroacupuncture at non-acu-point for 28 days. Learning and memory was tested by Morris water maze. Deposition ofβ-amyloid (Aβ) peptide was determined by immu-nohistochemical staining. The expression of BDNF in cortex was examined by RT-PCR and Western blotting. Results Compared with the model group, DU20 group ameliorated the learning and memory ability of APP/PS1 double-transgenic mice (P<0.05), decreased the deposi-tion of Aβpeptide (P<0.05) and upregulated the gene and protein levels of BDNF (P<0.01). There was no significant difference between the model group and non-acupoint group (P>0.05). Conclusion Electroacupuncture at DU20 acupoint could ameliorate learning and memory in APP/PS1 double-transgenic mice. The mechanism may be related to increase the expression of BDNF and decrease the deposition of Aβ.
5.Improvement Effects of Bee Venom Plastics on Experimental Cerebral Thrombosis in Rats
Miao HE ; Zhixue ZHANG ; Hairong ZHAO ; Xiumei WU ; Yu ZHAO ; Chenggui ZHANG
China Pharmacy 2019;30(2):182-187
OBJECTIVE: To study the improvement effects of Bee venom(BV) plastics on experimental cerebral thrombosis in rats. METHODS: Totally 96 SD rats were randomly divided into sham operation group (normal saline), model group (plastics blank matrix), Nimodipine group (positive drug, 4.00 mg/kg) and BV plastics low-dose, medium-dose, high-dose groups (1.67, 3.33, 6.67 mg/kg), with 16 rats in each group. Rats in sham operation group and Nimodipine group were given medicine intragastrically, while rats in model group and BV plastics groups were given medicine by transdermal smearing. After 5 days of continuous administration, the experimental cerebral thrombosis model was established by ligating the right external carotid artery and pterygomandibular artery, and injecting compound thrombus inducer into the internal carotid artery. The wet mass ratio of right brain to left brain was measured to investigate the degree of brain edema on the infarcted side. The content of Evans blue (EB) in the left and right hemispheres of rats was determined by ultraviolet spectrophotometry to investigate the cerebral vascular permeability. Blood rheology and coagulation function indicators of rats were measured. The pathological changes of brain tissue in rats were observed by HE staining, and the number of survival neuron cells was counted. RESULTS: Compared with the indexes of sham operation group, the cerebral thrombosis model was established successfully. Compared with model group, the area of blue staining in the right brain (infarcted side) of rats in BV plastics groups was significantly reduced, and the right brain/left brain wet mass ratio and the content of EB in the right brain tissue were significantly reduced (P<0.05 or P<0.01). The whole blood viscosity and Casson viscosity of rats in BV plastics groups, and the plasma viscosity of rats in BV plastics medium-dose and high-dose groups decreased significantly (P<0.01). PT and APTT of rats were prolonged significantly in BV plastics medium-dose group (P<0.01). The pathological changes of brain tissue in rats in BV plastics groups were significantly alleviated. The arrangement of neuron cells was more orderly, the shape and structure of cells were clear, the nucleolus was clear, the membrane was intact, and the number of survival neuron cells was significantly increased (P<0.01). CONCLUSIONS: BV plastics can alleviate brain edema, inhibit cerebral vascular permeability, improve hemorheology and coagulation function indicators of rats after the formation of cerebral thrombosis, and alleviate nerve cell injury after ischemia.
6.Drug resistance and genetic background of New Delhi metallo-β-lactamase ( NDM )-producing bacterial strains in Lishui area of Zhejiang province
Jiansheng HUANG ; Jinglu YU ; Yan ZHU ; Xiaolei HU ; Jianmin REN ; Yunan ZHAO ; Hui DING ; Rongzhen WU ; Zhigang ZHAO
Chinese Journal of Clinical Infectious Diseases 2018;11(4):287-293
Objective To analyze the drug resistance phenotype and genetic background of New Delhi metallo-β-lactamase (NDM)-producing bacterial strains in Lishui area of Zhejiang province.Methods The imipenem-resistant Enterobacteriaceae strains were isolated from January 2012 to December 2016 in Lishui Municipal Central Hospital of Zhejiang Province.Mrieux Vitek 2 Compact system was used to identified strains and PCR was used to screen for blaNDMgene.Susceptibility was detected by K-B method and MICs were obtained by Vitek 2 with GN13 cards.Plasmids typing was carried out by DNA sequencing of the replication initiator with the transconjugates as templates.The blaNDMgenetic contexts were detected by PCR and complete genome sequencing.Results A total of 102 strains of carbapenem-resistant enterobacteria (CRE), mainly Escherichia coli and Enterobacter cloacae, were isolated, of which 15 were positive for blaNDMwith a positive detection rate of 14.7%.The resistance rate to β-lactam antibiotics was 100%, and the resistance rates to aztreonam, compound sulfamethoxazole , tobramycin and gentamicin were all >80%;and the resistance rate to quinolones was >50%.Among the 15 NDM-producing strains , 12 strains were positive for Hodge test, and 2 strains of Enterobacter cloacae and 1 strain of Escherichia coli were negative. There were 11 strains of blaNDM-1and 4 strains of blaNDM-1.A variety of plasmid types such as IncX 3, IncFIIγ and IncA/C were detected, and 4 blaNDM-5genes were located in the IncX3 plasmid.Four blaNDMsurrounding gene structures were found, of which 8 blaNDM-1genes were located in ISAb125-hyp-blaNDM-1-bleMBL-TrpF-DsbC-IS26, while blaNDM-5was located in IS3000-IS5-blaNDM-5-bleMBL-TrpF-DsbC-IS26 structure, and the former was reported for the first time in China.Conclusion NDM-producing bacterial strains in Lishui area are prevalent at a low level and have high sensitivity to fosfomycin and polymyxin .The blaNDMgene may have multiple sources, but IncX3 plasmid is still the main source for gene transfer.Some new types of blaNDM-1 gene structure have been also found in this study.
7.Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma
Mengjia WU ; Yunan WANG ; Bo HE ; Yanyi LU ; Junzhu XU ; Zixuan SU ; Fengmin YIN ; Shujun LIU ; Yuju BAI ; Wei HU
Chinese Journal of Radiation Oncology 2023;32(6):519-525
Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.
8.Diagnosis and treatment of humeral medial epicondyle fracture combined with radial neck fracture in children and adolescents
Yunan LU ; Ran LIN ; Jiazhang WU ; Jinchen CHEN ; Tianlai CHEN ; Yuling HUANG ; Shunyou CHEN
Chinese Journal of Orthopaedic Trauma 2023;25(2):142-146
Objective:To explore the diagnosis and treatment of humeral medial epicondyle fracture combined with radial neck fracture in children and adolescents.Methods:The clinical data were retro-spectively analyzed of the 12 pediatric patients with fractures of the humeral medial epicondyle plus the radial neck who had been admitted from February 2015 to August 2021 to Department of Pediatric Orthopedics, The Second Hospital of Fuzhou. There were 6 males and 6 females, with an age of (11.1 ± 2.5) years. According to the Papavasiliou classification, the humeral medial epicondyle fractures were type Ⅱ in 7 cases, type Ⅲ in 2 cases and type Ⅳ in 3 cases; according to the Judet classification, the radial neck fractures were type Ⅰ in 3 cases, type Ⅱ in 4 cases and type Ⅲ in 5 cases. Two Judet-Ⅰ radial neck fractures were missed by X-ray exam-ination but diagnosed by CT examination. Of the humeral medial epicondylar fractures, 9 were treated by open reduction and hollow screwing and 3 by closed reduction and Kirschner wiring. Of the radial neck fractures, 8 were treated by closed reduction and elastic intramedullary nailing and 4 conservatively. Fracture healing was followed up by postoperative radiographs. At the last follow-up, the carrying angles were measured, Kim Elbow Function Score (KEPS) was used to evaluate the functional recovery of the injured limb, and related complications were recorded.Results:All the 12 patients were followed up for (40.0±25.6) months. Fractures headed after (6.3±1.2) weeks. At the last follow-up, the carrying angle was 15.5°±2.6° on the injured side and 14.7°±2.0° on the healthy side, showing no significant difference ( P>0.05); KEPS was (96.3±5.3) points on the injured side and (98.8±2.3) points on the healthy side, showing no significant difference either ( P>0.05). No incision infection, bone nonunion, elbow valgus, joint stiffness or other complications were found; the postoperative elbow stability recovered well. Conclusions:As the fracture of the humeral medial epicondyle combined with the radial neck fracture is a special type of injury of straightened elbow during valgus stress in children and adolescents, it is likely to be missed in diagnosis. The goal of treatment is good functional recovery by restoring the articular match and elbow stability.
9.Ershiwuwei Guijiu Pill Activates PI3K/Akt/mTOR-mediated Autophagy to Alleviate Osteoporosis in Ovariectomized Rats
Yunan JIANG ; Lixue ZHANG ; Fanglin DUAN ; Yao YU ; Fenghui LI ; Lina MA ; Peifeng WU ; Changxing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):43-51
ObjectiveTo investigate the mechanism of Ershiwuwei Guijiu pill in preventing and treating postmenopausal osteoporosis (PMOP) by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway and inhibiting excessive autophagy. MethodFemale SD rats were ovariectomized and randomly divided into the sham operation group (Sham), the operation group (OVX), the Ershiwuwei Guijiu pill (GJ) group, and the raloxifene hydrochloride (RLX) group, with 10 rats in each group. Enzyme-linked immunosorbent assay (ELISA) and colorimetric methods were used to detect the levels of estrogen, bone metabolism markers in serum, and total superoxide dismutase (T-SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in tibial tissue. Flow cytometry was used to detect reactive oxygen species (ROS) levels in bone marrow mesenchymal stem cells. Masson staining was used to observe pathological changes in the proximal tibia, and micro-computed tomography (Micro-CT) was used to observe changes in tibial microstructural parameters. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the expression of autophagy-related proteins Beclin1, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 (Atg5), as well as PI3K, Akt, and mTOR in tibial tissue. ResultCompared with the Sham group, the OVX group showed a significant decrease in serum levels of estradiol (E2) and calcium ion (Ca2+), and T-SOD, GSH-Px, PI3K, Akt, and mTOR mRNA levels in bone tissue (P<0.05, P<0.01), significantly reduced bone mineral density (BMD), bone surface/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular connectivity (Con) in the tibia (P<0.05, P<0.01), thinner epiphyseal growth plate, and the bone marrow cavity filled with fat vacuoles. Moreover, the levels of phosphorus (P), MDA, ROS, and mRNA and protein expression of Beclin1, LC3, and Atg5, as well as trabecular separation (Tb.Sp) were significantly elevated (P<0.05, P<0.01). Compared with the OVX group, the GJ and RLX groups showed significant increases in serum E2 and Ca2+, and bone tissue levels of SOD, GSH-Px, and the mRNA levels of PI3K, Akt, and mTOR (P<0.05, P<0.01), significantly increased BMD, BS/BV, Tb.Th, Tb.N, and Con in the tibia, thickened epiphyseal growth plate, and significantly reduced fat vacuoles in the bone marrow cavity (P<0.05, P<0.01). Additionally, the levels of P, MDA, ROS, Beclin1, LC3, Atg5 mRNA and proteins, and Tb.Sp were significantly decreased (P<0.05, P<0.01). The ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR, which were significantly reduced in the OVX group (P<0.01), were significantly increased in the GJ and RLX groups (P<0.01). ConclusionThe Ershiwuwei Guijiu pill reduces oxidative stress and inhibits autophagy, thereby preventing and treating postmenopausal osteoporosis. Its mechanism may be related to the activation of the PI3K/Akt/mTOR signaling pathway, which inhibits autophagy.
10.Changes of proportion regarding consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above.
C ZHOU ; W DONG ; Z Y WU ; M H JIA ; Y F LI ; Y J ZHOU ; G J TAN ; X CHEN ; J ZHENG ; K M ROU
Chinese Journal of Epidemiology 2018;39(6):745-749
Objective: To investigate the changes of proportion on both consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above (LFSW), in order to provide evidence for targeted intervention strategies. Methods: A total of six cities-Liuzhou city and Pingnan couty of Guigang city of Guangxi Zhuang Autonomous Region, Jinghong city of Xishuangbanna Dai autonomous prefecture and Dali city of Dali Bai autonomous prefecture of Yunnan province, Zhangjiajie city and Jianghua Yao autonomous county of Yongzhou city Hunan province were involved in this study, with 60 eligible participants needed in each city, estimated through a pre-study. The first cross-sectional survey was completed from October 2012 to January 2013. Face-to-face questionnaire interview was carried out to collect information on socio-demography, work-related information and condom use situation. Blood was collected for syphilis testing. The second cross-sectional survey was carried out from June to September, 2015 under the same procedure. Results: A total of 371 and 403 eligible participants were included in the first and second survey, respectively. When comparing the two surveys, we noticed that the average age showed a slight change, from 42.4 years to 43.8 years old (t=3.537, P<0.001) and the average price for every commercial sex exchange increased from 36.8 RMB to 49.5 RMB (t=11.961, P<0.001). In the first survey, 46.9% (174/371) of the participants had more than two years of experience working as LFSW, compared to 61.3% (247/403) in the second survey (χ(2)=16.125, P<0.001). Also, 46.9% (174/371) of the participants consistently used condoms with clients in the past month in the first survey versus 64.3% (259/403) (χ(2)=23.641, P<0.001) in the second one. Rates of syphilis infection were found from 15.9% (59/371) in the first survey reduced to 7.2% (29/403) in the second survey (χ(2)=14.533, P<0.001). Conclusion: Compared with the first survey, the proportion of consistent condoms use showed an increase. Although the proportion of syphilis infection decreased in the second survey, the scope did not meet the criteria on syphilis, set by the government. Targeted intervention strategies on condom promotion and syphilis control should be implemented consistently in this population.
Adult
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China/epidemiology*
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Condoms/trends*
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Cross-Sectional Studies
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Female
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Humans
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Prevalence
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Risk Factors
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Safe Sex
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Sex Work
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Sex Workers
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Sexually Transmitted Diseases/epidemiology*
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Surveys and Questionnaires
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Syphilis/prevention & control*
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Syphilis Serodiagnosis