1.Maternal liver damage induced by cadmium exposure in pregnant mice through hypoxia inducible factor-1α-mediated upregulation in DRP1
Limin DAI ; Hualong ZHU ; Yongwei XIONG ; Weibo LIU ; Guoxiang ZHOU ; Shuang ZHANG ; Zhengjia LING ; Lulu TAN ; Jin ZHANG ; Yufeng ZHANG ; Yiting FU ; Daixin LI ; Hua WANG
Journal of Environmental and Occupational Medicine 2023;40(1):68-75
Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg−1), and a high-dose cadmium group (HCd group: 5 mg·kg−1). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl2) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl2 (10 μmol·L−1) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl2 (10 μmol·L−1) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl2 (10 μmol·L−1) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P<0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P<0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl2 for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.
2.Systematic implementation of World Health Organization rehabilitation competency framework in rehabilitation: conceptual framework, approaches and application
Zhuoying QIU ; Kin Fun Joseph KWOK ; Hongwei SUN ; Shicai WU ; Jun LV ; Meilin YAO ; Guoxiang WANG ; Fubing QIU ; Yan LU ; Guangxu XU ; Linhong JI ; Qi JING ; Di CHEN ; Chuanping HAO ; Anqiao LI ; Shaopu WANG ; Xiaofei XIAO
Chinese Journal of Rehabilitation Theory and Practice 2022;28(3):265-274
Objective To systematically analyze the World Health Organization Rehabilitation Competency Framework (RCF) theoretical framework, methodology and its application in the field of rehabilitation.Methods We systematically analyzed RCF conceptual framework and key characteristics, and discussed how to apply the RCF in the fields of human resource planning, education program and curriculum system, and vocational competency standards and certification criteria for rehabilitation human resources.Results The RCF encompasses five domains, naming practice, professionalism, learning and development, management and leadership, and research. Rehabilitation professionals' performance is the result of the interaction of their core values and beliefs, competencies, activities, knowledge, and skills. The RCF can be used to plan rehabilitation human resources, establish competency-based rehabilitation education programs and curriculum systems, and develop competency certification standards and licensure accreditation standards.Conclusion This study analyzed background, content and implementation framework of RCF, and systematically discussed the theories and methods related to how to use the RCF to construct national rehabilitation human resources development plans, develop rehabilitation education programs and curriculum systems based on the RCF, and establish certification and assessment standards for rehabilitation human resources.
3.Establishment of an intestinal organoid-based method to investigate the radiation mitigation effect of Epiregulin
Guoxiang FU ; Yuanchuang LI ; Mengxue PAN ; Qiang GUO ; Xinxin RAO ; Xiaoya XU ; Yi ZHOU ; Chunlin SHAO ; Jianjun GAO ; Guoqiang HUA
Chinese Journal of Radiological Medicine and Protection 2018;38(9):641-646
Objective To establish an intestinal organoid-based assay to investigate the radiation mitigation effect of epiregulin in vitro. Methods Intestinal crypts were released from tissue incubated with EDTA. Intestinal crypts seeded in 3D matrigel were irradiated at 24 h after plating. The radiation mitigation effect of epiregulin was evaluated by measuring the survival rate, size and budding numbers of the organoid after irradiation, and the basic FGF was used as a positive control of epiregulin. Results Radiation-induced lethality and dose-dependent survival curve of the intestinal organoid were consistent with in vivo data. Treatment with epiregulin (400 ng/ml) at 24 h post-radiation significantly increased survival rate of 8 Gy X-ray irradiated intestinal organoid in comparison with non-treated group [(12.56 ± 1.02)%vs. (4.73 ± 0.38)%, t=12.43,P<0.05]. Conclusions Epiregulin has radiation mitigation effect on intestinal organoid and could serve as a potential medical countermeasure to mitigate gastrointestinal toxicity.
4.Effect of mild hypothermia on expression of phosphorylated eukaryotic translation initiation factor 2α in hippocampus in a mouse model of cerebral ischemia-reperfusion
Jie ZHAO ; Haifang WAN ; Guoxiang WANG ; Yunbin FU ; Yan ZHANG
Chinese Journal of Anesthesiology 2017;37(8):1013-1016
Objective To evaluate the effect of mild hypothermia on the expression of phosphorylated eukaryotic translation initiation factor 2α (p-eIf2αt) in the hippocampus in a mouse model of cerebral ischemia-reperfusion (I/R).Methods Sixty pathogen-free healthy male C57BL6 mice,aged 8-12 weeks,weighing 20-30 g,were divided into 3 groups (n =20 each) using a random number table:sham operation group (group S),group I/R and mild hypothermia group (group H).Cerebral I/R was induced by 15-min occlusion of bilateral common carotid arteries followed by reperfusion in chloral hydrate-anesthetized mice.Surface cooling was started immediately after reperfusion to maintain the rectal temperature at 32-34 ℃ for 3 h in group H.The neurologic deficit score was evaluated at 24 h of reperfusion.The mice were then sacrificed,brains were immediately removed,and hippocampi were isolated for examination of pathologic changes of hippocampal CA1 region and for determination of neuroapoptosis (by TUNEL) and expression of peIf2α (by Western blot).The apoptosis rate was calculated.Results Compared with group S,the neurologic deficit scores at 24 h of reperfusion and apoptosis rate of hippocampal neurons were significantly increased,and the expression of p-eIf2α was up-regulated in I/R and H groups (P<0.05).Compared with group I/R,the neurologic deficit scores at 24 h of reperfusion and apoptosis rate of hippocampal neurons were significantly decreased,and the expression of p-eIf2α was down-regulated in group H (P< 0.05).Conclusion Mild hypothermia reduces endoplasmic reticulum stress and inhibits neuroapoptosis through inhibiting the expression of p-eIf2α in the hippocampus in a mouse model of cerebral I/R.
5.Dose-response relationship of sufentanil blunting responses to double-lumen endotracheal intubation when combined with propofol given by TCI in patients with pulmonary tuberculosis
Hong LUO ; Fan TAO ; Guoxiang WANG ; Lixia HUANG ; Haifang WAN ; Hao FAN ; Yunbin FU ; Wensheng ZHAO
Chinese Journal of Anesthesiology 2017;37(2):199-201
Objective To determine the dose-response relationship of sufentanil blunting responses to double-lumen endotracheal intubation when combined with propofol given by target-controlled infusion (TCI) in patients with pulmonary tuberculosis.Methods One hundred patients of both sexes with pulmonary tuberculosis,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 24-58 yr,with body mass index <30 kg/m2,with Mallampati grade Ⅰ or Ⅱ,undergoing thoracic surgery under general anesthesia,were divided into Ⅰ-Ⅴ groups (n =20 each) using a random number table.Anesthesia was induced with iv sufentanil 0.35 μg/kg (group Ⅰ),0.40 μg/kg (group Ⅱ),0.45 μg/kg (group Ⅲ),0.50 μg/kg (group Ⅳ) and 0.55 μg/kg (group Ⅴ),and propofol TCI (target plasma concentration 3.5 μg/ml) and iv vecuronium 0.15 mg/kg.The patients were endotracheally intubated and mechanically ventilated.The response to double-lumen endotracheal intubation was defined as positive when mean arterial pressure increased by> 20% of the baseline value and/or heart rate > 90 bpm within 5 min after intubation.The median effective dose (ED50),ED95 and 95% confidence interval (95% CI) of sufentanil blunting the responses to double-lumen endotracheal intubation were calculated by Probit analysis.Results The ED50 (95% CI) and ED95 (95% CI) of sufentanil blunting the responses to intubation were 0.411 (0.370-0.441) μg/kg and 0.635 (0.556-0.888) μg/kg,respectively,when combined with propofol given by TCI.Conclusion When combined with propofol given by TCI (target plasma concentration 3.5 μg/ml),the ED50 and ED95 of sufentanil blunting the responses to double-lumen endotracheal intubation are 0.411 and 0.635 μg/kg,respectively,in patients with pulmonary tuberculosis.
6.Rehabilitation 2030: Meet Ever-increasing Rehabilitation Needs
Xin LI ; Zhuoying QIU ; Jian YANG ; Di CHEN ; Joseph KWOK ; Xianguang WU ; Hongmei SHI ; Guoxiang WANG ; Jie ZHU
Chinese Journal of Rehabilitation Theory and Practice 2017;23(4):380-384
This paper discussed the gap between the unmet needs and services of rehabilitation at global level and advocated implementation of "WHO Global Disability Action Plan 2014-2021". The following recommendations had been made: expanding coverage, improving quality, enhancing monitoring, and integrating data of functioning and disability, and rehabilitation into national health information system. It is important to develop rehabilitation to meet clients' rehabilitation needs to promote realization of the United Nations Sustainable Development Goals 2030 (SDGs).
7.Analysis of the variation trends of bed allocation and its equity at primary medical institutions in China
Wenqi FU ; Guoxiang LIU ; Qunhong WU ; Mo HAO
Chinese Journal of Hospital Administration 2016;32(3):217-220
Objective Measure the variation trend and the problems of bed allocation and its equity at primary medical institutions and provide theoretical basis for optimizing the policy of health resources allocation for the government.Methods Analysis of the distribution and equity of the inpatient beds at primary medical institutions in terms of geographical area by means of the survey of regular overall statistics forms and the methods of Gini coefficient and Theil index.Results From 2009 to 2012,the number increase of beds at such institutions geographically was 7.72%,while that in eastern,central and western regions of China were respectively 5.35%, 3.97% and 27.88%.The number increase at community healthcare centers was 46.58%,while that in eastern,central and western regions of the country were respectively 18.09%,29.57%和 81.53%.The number increase at township hospitals was 2.33%,while that in eastern,central and western regions were respectively - 3.83%,- 0.43% and 22%.The Gini coefficient of bed allocation at such institutions was beyond 0.6,while that in eastern, central and western regions were respectively under 0.3,0.3-0.4 and 0.6 above.The Gini coefficient of bed allocation at community healthcare centers fell from above 0.4 to under 0.4.The Gini coefficient in the western regions increased from 0.3-0.4 to over 0.4.The variation trend of township hospitals was similar with the overall conditions at such institutions.The intra-regional Theil indexes and their contribution rates of bed allocation at such institutions were higher than those of inter-regional. Conclusions The overall variation trend of bed allocation at such institutions was on the rise,yet its variation trend of equity remains unchanged.The bed allocation and its equity at such institutions were higher than those at township hospitals.The growth rate in western regions was the highest,but the absolute number was the lowest.Moreover,the equity of bed allocation in such regions was not only the lowest,but also was found rising.The influence of bed allocation in intra-region terms was large,while its equity was not only lower but falling as well.
8.Clinicopathologic features of solitary fibrous tumor in urogenital system
Huajuan RUAN ; Aihua HUANG ; Sheng CHENG ; Guoxiang FU
Chinese Journal of Pathology 2016;45(4):248-251
Objective To study the clinicopathologic features and differential diagnosis of solitary fibrous tumor ( SFT) in the urogenital system.Methods The clinical data and pathologic characteristics of eight cases of SFT in the urogenital system were analyzed, and the relevant literature was reviewed.Results The cohort included six male and two female patients, with age of onset ranging from 25 to 80 years.Five occurred in the kidney ( three in the right kidney) , one case each occurred in the bladder, the prostate and the spermatic cord.Most patients showed no obvious clinical symptoms or only had low back pain and swelling.The diameter of the tumor was ranged from 2.5 to 11.8 cm (median 5.2 cm).Microscopy showed at low magnification, the tumor cells were spindle-shaped and arranged in bundles or helicoid pattern.The regional mesenchymal fibroblasts showed hyperplasia, with obvious collagenization and formed hemangiopericytoma-like structure.One case showed increased mitotic figures ( >5 cells/10 HPF) and focal necrosis.By immunohistochemistry, the tumor cells were positive for CD34 and STAT6 in all eight cases, CD99 and vimentin in six cases, bcl-2 in four cases and SMA in one case.All seven cases with follow-up did not show any tumor recurrence or metastasis.Conclusions SFT is rare in the urogenital system and most patients show good prognosis.SFT expresses CD34 and STAT6 and needs to be distinguished from other spindle cell tumors.
9.Accuracy of immunochemical faecal occult blood test for colorectal cancer: meta-analysis.
Yansong JIANG ; Guoxiang LIU ; Huiyao HUANG ; Weidong HUANG ; Xin ZHANG ; Wenqi FU ; Min DAI ; Jufang SHI
Chinese Journal of Preventive Medicine 2015;49(5):392-398
OBJECTIVETo assess the accuracy of immunological fecal occult blood test (iFOBT) for detection of colorectal cancer (CRC).
METHODSA total of 1 197 studies published before June 2014 were selected from PubMed and Embase and 17 of which were finally included in this meta-analysis. A bivariate mixed-effects models was used for overall value merging and heterogeneity testing. In addition to the overall sensitivity and specificity, the analyses were also performed among certain subgroups, including a "colonoscopy group" (all were referred for colonoscopy diagnosis regardless screening results) and a "follow-up group" (only the screening positive were referred and all were then followed up), a qualitative group and a quantitative group (classified by the way of iFOBT result reading).
RESULTSA total of 161 502 subjects aged from 48 to 63 years were included in the analysis. IFOBT had an overall integrated sensitivity of 0.85 (95% CI: 0.79-0.89) (heterogeneity test: Q = 59.67, P < 0.001) and an overall integrated specificity of 0.93 (95% CI: 0.92-0.94) (heterogeneity test: Q = 1 722.53, P < 0.001) for detection of CRC. In the subgroup analysis, it was found that in the "colonoscopy group" and in the "follow-up group", the sensitivity were 0.81 (95%CI: 0.73-0.87) and 0.88 (95% CI: 0.81-0.92), respectively; the specificity were 0.92 (95% CI: 0.89-0.93) and 0.95 (95% CI: 0.94-0.96), respectively. It was also found that in the qualitative group and the quantitative group, the sensitivity were 0.84 (95% CI: 0.76-0.90) and 0.86 (95% CI: 0.78-0.92), respectively; the specificity were 0.94 (95% CI: 0.91-0.96) and 0.93 (95% CI: 0.91-0.94), respectively.
CONCLUSIONIFOBT had high overall sensitivity and specificity for detecting colorectal cancer.
Colonoscopy ; Colorectal Neoplasms ; Hematologic Tests ; Humans ; Mass Screening ; Occult Blood ; Sensitivity and Specificity
10.Related factors of hemodynamic damage after carotid artery stenting
Jintao HAN ; Haiyan ZHAO ; Xuan LI ; Qingyuan HE ; Shan YE ; Guoxiang DONG ; Jun FU ; Jingyuan LUAN ; Changming WANG ; Tianrun LI
Journal of Peking University(Health Sciences) 2015;(5):804-808
Objective:To analyze correlation factors of hemodynamic damage after carotid artery stenting.Methods:In this study, 66 cases (71 lesions) who undertook carotid artery stenting were col-lected and the correlation factors of hemodynamic damage were analyzed .Results:Hemodynamic damage emerged in 23 cases (32.4%), of which, 11.3%developed hypotension.The distance between bifurca-tion and lesions (P=0.002 0), plaque distribution (P=0.000 2), plaque character (P=0.001 9), post-dilation ( P =0.002 6 ) were associated with hemodynamic damage by single factor analysis . However, only eccentric plaque (P=0.015 3) and calcified plaque (P=0.009 7) were associated with hemodynamic damage by multiple factors analysis .All the patients could reach stable circulation by drugs during operation , and no cerebral ischemic events ( transient ischemic attack or stroke ) and cardiovascu-lar ischemic events happened .Conclusion: The distance between bifurcation and lesions , eccentric plaques, calcified plaques are correlation factors of hemodynamic damage .


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