1.Exogenous GDF11 improves vascular remodeling in hypertensive rats by regulating LOX-1-mediated endoplasmic reticulum stress pathway
Zhengdong DAI ; Liangkun HU ; Wei WAN ; Lixin XU
Chinese Journal of Arteriosclerosis 2024;32(10):850-856
Aim To investigate the effect of exogenous growth differentiation factor 11(GDF11)on vascular re-modeling in hypertensive rats through regulating the endoplasmic reticulum stress pathway mediated by lectin-like oxidized low density lipoprotein receptor-1(LOX-1).Methods Rats were randomly divided into control group,model group(Ang Ⅱ-induced hypertension rat model group),r-GDF11 group,Ab-LOX-1 group,r-GDF11+r-LOX-1 group,with 10 rats in each group.The changes of caudal arterial blood pressure in rats were detected by animal non-invasive blood pres-sure meter;the morphology of aortic vessels was evaluated by hematoxylin-eosin(HE)staining;the collagen deposition in aortic tissue was evaluated by Masson staining;the expression of GDF11,LOX-1 and endoplasmic reticulum(ER)stress related proteins in aortic tissues were detected by Western blot.Results Compared with the control group,the blood pressure of rats in the model group was increased,the media thickness(MT)and MT/lumen diameter(LD)of aortic tis-sue were increased,and the LD of aortic tissue was decreased(all P<0.05);Collagen volume fraction(CVF)value,the expression of glucose regulated protein 78(GRP78)and activating transcription factor 6(ATF6)protein,the ratio of phosphorylated PKR-like endoplasmic reticulum regulating kinase(p-PERK)/PERK and phosphorylated inositol requiring enzyme 1α(p-IRE1α)/IRE1α in aortic tissue were increased(all P<0.05).Compared with the model group,the blood pressure of rats in the r-GDF11 group and Ab-LOX-1 group was decreased,the MT and MT/LD of aortic tissue were de-creased,and the LD of aortic tissue was increased(all P<0.05);CVF value,the expression of GRP78 and ATF6 protein,p-PERK/PERK and p-IRE1α/IRE1α in aortic tissue were decreased(all P<0.05).Compared with the r-GDF11 group,the blood pressure of rats in the r-GDF11+r-LOX-1 group was increased,the MT and MT/LD of aortic tissue were increased,and the LD of aortic tissue was decreased(all P<0.05);CVF value,the expression of GRP78 and ATF6 protein,the p-PERK/PERK and p-IRE1α/IRE1α in aortic tissue were increased(all P<0.05).Conclusion Exogenous GDF11 im-proves vascular remodeling in hypertensive rats through inhibiting LOX-1-mediated endoplasmic reticulum stress pathway.
2.Efficacy and safety of ultrasound cycloplasty in the treatment of refractory glaucoma
Zhuang MIAO ; Changjun LAN ; Zhengdong XU ; Yue YANG ; Menglan ZHOU
International Eye Science 2024;24(6):985-989
AIM: To evaluate clinical efficacy and safety of ultrasound cycloplasty(UCP)in the treatment of refractory glaucoma.METHODS:From June 2021 to October 2022, a total of 17 patients(17 eyes)with refractory glaucoma were enrolled in this prospective study, and they all underwent UCP. The patients underwent 6 mo followed-up post-treatment, and the intraocular pressure(IOP), pain grade score, IOP lowering drugs, success rate and occurrence of complications were documented.RESULTS:The IOP was significantly decreased from 51.98±7.80 mmHg before UCP to 32.54±13.21 mmHg at 1 d, 22.38±11.98 mmHg at 1 wk, 22.63±10.78 mmHg at 1 mo, 26.05±9.17 mmHg at 3 mo, and 23.73±9.60 mmHg at 6 mo postoperatively(all P<0.01). The percentage of IOP reduction after treatment was 36.25%, 57.10%, 56.35%, 49.16% and 54.09% at 1 d, 1 wk, 1, 3, and 6 mo, respectively. The pain grade scores were decreased(P<0.01). There was a statistically significant reduction in the use of IOP lowering medications(P=0.008). At 6 mo postoperatively, 2 eyes(12%)were complete success, 11 eyes(65%)were qualified success, and 4 eyes(24%)were failure. The main complication observed was anterior chamber inflammation in 1 eye(6%), foreign body sensation in 2 eyes(12%), subconjunctival hemorrhage in 2 eyes(12%), and conjunctival congestion in 6 eyes(35%). All symptoms spontaneously resolved within 1 wk without requiring any specific treatment. One case of choroidal detachment(6%)occurred on 10 d postoperatively, but recovered after orally treated by prednisone acetate for 1 mo. No other serious complications, such as hyphema, corectopia, synechia or macular edema were reported.CONCLUSION:UCP is safe and efficacious in treating refractory glaucoma, reducing IOP and alleviating ocular pain symptoms, while maintaining a favorable safety profile.
3.Effects and mechanism of galangin on hepatocyte apoptosis in rats with obstructive jaundice
Lin ZHAO ; Zuowu XI ; Shasha XU ; Xubiao PAN ; Weisheng GUO
China Pharmacy 2024;35(18):2246-2251
OBJECTIVE To investigate the effects and mechanism of galangin (GAL) on hepatocyte apoptosis in rats with obstructive jaundice (OJ) based on the Janus kinase 2 (JAK2)/signal transduction and activator of transcription 3 (STAT3) signaling pathway. METHODS Taking male SD rats as the object, the OJ model was established by double ligation of common bile duct, and 48 rats with successful modeling were randomly separated into OJ model group (model group), low-dose GAL group (GAL-L group), high-dose GAL group (GAL-H group) and high-dose GAL+JAK2 activator colivelin group (GAL-H+ colivelin group), with 12 rats in each group; another 12 SD rats with laparotomy/abdominal closure without ligation were selected as sham operation group (sham group). Each administration group was given relevant medicine intragastrically and/or intraperitoneally, once a day, for 7 consecutive days. After the last medication, the morphology of liver tissue in rats was observed; the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), alanine transaminase (ALT) and γ -glutamyltransferase (GGT), as well as the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in mail:guoweishengjcy@126.com liver tissue were detected. The apoptotic rate of liver tissue cells, the expression levels of signaling pathway-related proteins (phosphorylated JAK2, JAK2, phosphorylated STAT3, STAT3) and apoptosis-related proteins [B cell lymphoma 2 (Bcl-2), Bcl-2 related X protein (Bax)] were determined. RESULTS Compared with sham group, congestion of liver sinusoids, damage to liver lobules, disordered arrangement and swollen morphology of liver cells, the disappearance of nucleoli, and significant infiltration of inflammatory cells and fibrous tissue proliferation were observed in model group; the serum levels of TBIL, DBIL, ALT and GGT, the level of MDA in liver tissue, the apoptosis rate of liver cells, the protein expression of Bax, and the protein phosphorylation levels of JAK2 and STAT3 in liver tissue of model group were increased significantly (P<0.05); the level of SOD and the protein expression of Bcl-2 in liver tissue were decreased significantly (P<0.05). Compared with the model group, the pathological injuries of liver tissue were relieved in GAL-L group and GAL-H group, all quantitative indicators had significantly improved, and the effect of GAL-H group was more significant (P< 0.05). Colivelin could significantly reverse the improvement effects of GAL on liver injury and related indicators of OJ rats (P< 0.05). CONCLUSIONS GAL may inhibit liver cell apoptosis in OJ rats, improve liver function and alleviate oxidant stress, the mechanism of which may be associated with inhibiting JAK2/STAT3 signaling pathway.
4.Changes in nerve fiber thickness and vascular density in macula and optic disc after femtosecond laser assisted and conventional phacoemulsification
Menglan ZHOU ; Zhengdong XU ; Changjun LAN ; Yue YANG ; Zhengyang LUO ; Zhuang MIAO ; Biao LI
International Eye Science 2024;24(9):1461-1465
AIM: To observe the changes of nerve fiber thickness and vessel density in macula and optic disc following femtosecond laser-assisted and conventional phacoemulsification cataract surgery through optical coherence tomography angiography(OCTA).METHODS: A total of 65 cases(85 eyes)that diagnosed with age-related cataract and received surgery in Aier Eye Hospital(East of Chengdu)were included in this prospective nonrandomized controlled study. The patients were divided into two groups according to the surgery choice, with 23 cases(30 eyes)in femtosecond laser assisted group, and 42 cases(55 eyes)in traditional phacoemulsification group. OCTA was used to compare the changes in central macular thickness, thickness of nerve fiber layer in optic disc, vessel density and blood perfusion preoperatively, and at 1 d and 1 mo postoperatively.RESULTS: BCVA of patients in the two groups was significantly improved and IOP was significantly reduced at 1 mo postoperatively(all P<0.01). The macular nerve fiber layer thickness of the femtosecond laser-assisted group was increased at 1 d and 1 mo postoperatively(all P<0.05), while there was no statistical difference in the traditional phacoemulsification group before and after surgery(all P>0.05); there were significant differences in nerve fiber layer thickness in optic disc, vessel density and blood perfusion in both macula and optic disc of the traditional phacoemulsification group(all P<0.05), but there were no differences in the femtosecond laser assisted group(all P>0.05). Furthermore, there were no significant differences in foveal avascular zone area in the two groups of patients(all P>0.05).CONCLUSION: Femtosecond laser-assisted cataract surgery had less impact on retinal vessels.
5.Research on the doctors′ willingness of working at primary institutions and the economic incentive effect from the perspective of mental account
Yingbei XIONG ; Lu LI ; Kai XU ; Jieming CHEN ; Kunhe LIN ; Zhengdong ZHONG ; Xiao LIU ; Jin ZHOU ; Li XIANG
Chinese Journal of Hospital Administration 2022;38(7):500-504
Objective:To understand the incentive effect and influencing factors of the current economic incentive policy for medical alliances in Longhua District of Shenzhen(the alliance for short) on doctors′ willingness to work at primary medical institutions(the primary for short) from the perspective of mental account, and to explore the economic incentive effect of different economic incentive distribution methods on doctors′ willingness to work at the primary.Methods:The questionnaire was designed based on mental account theory. Random sampling was made in November 2019 for a questionnaire survey among doctors in two district-level medical institutions of the alliance in Longhua District of Shenzhen. The purpose was to analyze their inclination to work at the primary and their selection preferences for economic incentive distribution methods under the current economic incentive policy. The data were analyzed by descriptive analysis, and the influencing factors of doctors′ willingness to work at the primary were analyzed by χ2 test and binary logistic regression. Results:A total of 254 valid questionnaires were collected with an effective recovery rate of 90.7%. Among the respondents, 189(74.4%) were willing to work at the primary, 168(66.1%) chose to receive the economic incentives specifically for working at the primary, and 148 people(58.3%) hoped to receive such economic incentives immediately. Education background, self-rated economic income level of doctors and different payment methods of economic incentive for working at the primary had significant effects on their willingness to work at the primary( P<0.05). Conclusions:The current economic incentive policy of the alliance can meet the demands for economic incentives in terms of doctors′ material accounts, and doctors′ overall inclination to work at the primary was strong. If the amount of economic incentives is constant, doctors preferred to receive the economic incentives specifically, mainly affected by income accounts and additional income accounts. In addition, education and self-assessment of economic income level were important factors affecting the willingness of doctors to work at the primary, which may be affected by mental accounts other than material accounts.
6.Risk factors for lower extremity deep venous thrombosis in acute hemorrhagic stroke patients during intensive care unit period
Hongling ZHANG ; Youdong XU ; Zhengdong LIU
Chinese Journal of Neuromedicine 2020;19(5):488-492
Objective:To explore the risk factors affecting the occurrence of lower extremity deep venous thrombosis in patients with acute cerebral hemorrhage during intensive care unit (ICU) period.Methods:One hundred and thirty-five patients with acute cerebral hemorrhage who were transferred to ICU of our hospital from December 2016 to August 2019 were enrolled. The clinical data were collected, including gender, age, Glasgow coma scale (GCS) scores, hematoma volume, body mass index (BMI), systolic pressure, D-dimer, activated partial thromboplastin time, surgery before transfer, unplanned surgery during ICU period, and so on. According to occurrence of lower extremity deep venous thrombosis, these patients were divided into thrombosis group and non-thrombosis group; univariate analysis was used to compare the differences in clinical data between the two groups, and multivariate Logistic regression analysis was used to screen the independent risk factors for lower limb deep vein thrombosis, and the predictive efficacy was evaluated using receiver operating characteristic (ROC) curve.Results:Thirteen patients (9.63%) were diagnosed as having lower extremity deep venous thrombosis. There were statistical differences between two groups in GCS scores at admission, hematoma volume, BMI, D-dimer, platelet count, surgery before admission, unplanned surgery during ICU period, and hemostasis treatment ( P<0.05). Results of multivariate Logistic regression analysis showed that BMI, D-dimer, and unplanned surgery during ICU period were independent risk factors for lower extremity deep venous thrombosis ( OR=1.868, 95%CI: 1.147-3.043, P=0.012; OR=1.004, 95%CI: 1.000-1.008, P=0.037; OR=0.019, 95%CI: 0.001-0.446, P=0.014). ROC curve showed the area under the curve by combining these three factors was 0.982 ( P=0.000), with sensitivity of 92.31% and specificity of 96.72%. Conclusion:Acute cerebral hemorrhage patients with high BMI, high D-dimer level, and unplanned surgery during ICU period are more likely to have low extremity deep venous thrombosis during ICU period; these patients should be alerted in clinical process.
7.Vascular endothelial growth factor gene polymorphism and Stroke
Bingdong XU ; Hongcheng MAI ; Zhengdong WU ; Peizhi ZHU ; Yubin LIANG ; Yusheng ZHANG
International Journal of Cerebrovascular Diseases 2018;26(1):42-46
The incidence of stroke increases year by year.It seriously affects the quality of life in patients.The pathogenesis of stroke is related to a variety of factors,involving genetic polymorphisms,biochemical mechanisms,and inflammatory effect.Among them,vascular endothelial growth factor (VEGF) has become one of the hotspots of research on the pathogenesis of stroke in recent years.This article reviews the correlation between VEGF gene polymorphism and stroke.
8. Effects of hypoxia inducible factor-1α on P311 and its influence on the migration of murine epidermal stem cells
Zhengdong XU ; Haisheng LI ; Song WANG ; Weifeng HE ; Jun WU ; Gaoxing LUO
Chinese Journal of Burns 2017;33(5):287-294
Objective:
To explore the effects of hypoxia inducible factor-1α (HIF-1α) on P311 and its influence on the migration of murine epidermal stem cells (ESCs) under hypoxia in vitro.
Methods:
Two kinds of murine ESCs were isolated and obtained from 15 neonatal wild-type C57BL/6J mice and 5 congeneric source P311 gene knock-out mice, respectively. The first passage of cells were used in the following experiments after morphologic observation and detection of expression of cell surface markers CD71 and CD49f with flow cytometer. (1) After cell scratch assay, according to the random number table (the same dividing method below), ESCs of P311 gene knock-out mice were divided into normoxia group (cells were cultured with complete medium in normoxic carbon dioxide incubator, and the subsequent normoxic treatments were the same) and hypoxia group (cells were cultured in hypoxic carbon dioxide incubator containing 1% oxygen, and the subsequent hypoxic treatments were the same), with 12 inserts in each group. ESCs of wild-type mice were divided into normoxia group, pure hypoxia group, dimethyl sulfoxide (DMSO) control group (2 μL DMSO solvent was added for 1 h of normoxia treatment before hypoxia treatment), HIF-1α inhibitor group (cells were treated with 11 μmol/L HIF-1 inhibitor of 2 μL under normoxia condition for 1 h before hypoxia treatment), HIF-1α stabilizer group (the cells were treated with 2 μmol/L FG-4592 of 2 μL under normoxia condition for 1 h before hypoxia treatment), with 12 inserts in each group. Three inserts of each time point in each group were adopted respectively to measure the residual width of scratch under inverted phase contrast microscope at post scratch hour (PSH) 0 (immediately), 12, 24, and 48. (2) After hypoxia treatment, the protein level of HIF-1α in ESCs of wild-type mice was detected by Western blotting at post hypoxia hour (PHH) 0, 12, 24, and 48. (3) ESCs of wild-type mice were divided into pure hypoxia group, DMSO control group, HIF-1α inhibitor group, and HIF-1α stabilizer group as that of experiment (1) with the same treatment. The mRNA expression of P311 and expression of P311 in ESCs were determined by real-time fluorescent quantitative reverse transcription polymerase chain reaction and immunocytochemical staining, respectively, at PHH 0 (immediately), 12, 24, and 48 (with sample numbers of 12). (4) The second passage of human embryonic kidney 293 (HEK-293) cells were divided into empty vector hypoxia group (cells were cultured under hypoxia condition after being transfected with empty vector plasmid), P311 normoxia group (cells were cultured under normoxia condition after being transfected with P311 reporter gene plasmid), P311 hypoxia group (cells were cultured under hypoxia condition after being transfected with P311 reporter gene plasmid), P311 hypoxia+ HIF-1α inhibitor group (cells which were incubated with HIF-1α inhibitor were cultured under hypoxia condition after being transfected with P311 reporter gene plasmid). The luciferase activity was detected at post culture hour (PCH) 0 and 12, respectively, and then the P311 transcriptional regulatory binding site of HIF-1α and the promoter sequence of P311 were predicted and searched by bioinformatics methods. Data were processed with factorial design variance analysis, one-way analysis of variance, LSD test and Bonferroni correction.
Results:
(1) The results of ESCs. The cells showed cobblestone-like pattern and different clonal morphology due to the different cell proliferation potential. The proportion of CD71-CD49f+ cells accounted for about 85%. The identification results indicated that the cells showed strong stem cell properties and high purity. Compared with those in cells of normoxia group of P311 gene knock-out mice, the residual widths of scratch of cells in pure hypoxia group were smaller at PSH 12 and 24 (with
9.Clinical significance of detecting t(11;14) by fluorescence in situ hybridization for the diagnosis of 7 patients with atypical mantle cell lymphoma.
Jianfeng ZHU ; Zhengdong WU ; Lei FAN ; Wei XU ; Jianyong LI
Chinese Journal of Medical Genetics 2016;33(1):13-16
OBJECTIVETo study the clinical features and diagnosis of 7 patients with atypical mantle cell lymphoma (MCL).
METHODSThe 7 MCL patients were misdiagnosed as chronic lymphocytic leukemia (CLL) due to a score of 4 for their immunophenotypes. The clinical features and diagnosis of such patients were retrospectively analyzed.
RESULTSSix patients had superficial lymphadenectasis but their lymph nodes could not be palpated. All 7 patients were as stage IV considering bone marrow infiltration. Scores of immunophenotype of CLL were 4, and interphase fluorescence in situ hybridization (FISH) for t(11;14) were positive in all patients.
CONCLUSIONSome MCL patients have clinical features similar to CLL. Interphase FISH can play an important role in the diagnosis of MCL.
Aged ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Lymphoma, Mantle-Cell ; diagnosis ; genetics ; Male ; Middle Aged ; Translocation, Genetic
10.Neuron-secreted factors promote the growth of skeletal muscle cells
Mingxuan CAI ; Meichen WANG ; Zhicheng XU ; Nan YAN ; Xinyu MENG ; Zhengdong WANG
Chinese Journal of Tissue Engineering Research 2016;20(42):6324-6329
BACKGROUND:There is no effective treatment for muscle atrophy caused by peripheral nerve damage. Skeletal muscle cel s, a structural unit of muscle contraction, can be used for studies on muscle atrophy when cultured in vitro.
OBJECTIVE:To investigate the promotion effect of neuron-secreted factors on the growth of skeletal muscle cel s in vitro.
METHODS:Skeletal muscle cel s primary cultured in vitro were divided into two groups:experimental group with neuron-secreted factors, and control group with common culture medium, respectively. Afterwards, the number of skeletal muscle cel s and expression level of alpha actin were detected by hematoxylin-eosin staining and immunohistochemical staining, respectively.
RESULTS AND CONCLUSION:The number of skeletal muscle cel s and expression level of alpha actin in the experimental group were significantly higher than those in the control group (P<0.05). In conclusion, neuron-secreted factors have the ability of promoting the growth of skeletal muscle cel s and may be helpful for denervated muscle atrophy.

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