1.Moderating effect of salidroside on intestinal microbiota in mice exposed to PM2.5
Siqi LI ; Chen LIU ; Weihong XU ; Wenbo WU ; Ruixi ZHOU ; Limin ZHANG ; Chao SONG ; Yumei LIU ; Fengjiao TAN ; Mengxiao LUAN ; Xiaolin HAN ; Jinfeng TAN ; Li YU ; Dongqun XU ; Qin WANG ; Xiaohong LI ; Wanwei LI
Journal of Environmental and Occupational Medicine 2024;41(2):125-132
Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.
2.Effect of vitamin C on intestinal flora disorders in Cr(VI)-contaminated mice
Limin ZHANG ; Chen LIU ; Yumei LIU ; Xueqian WU ; Ming SHU ; Jian ZHOU ; Dongqun XU ; Qin WANG ; Wanwei LI ; Xiaohong LI
Journal of Environmental and Occupational Medicine 2024;41(7):807-813
Background Hexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. Objective To investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. Methods Thirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K2Cr2O7, Cr(VI)], and VC+K2Cr2O7 [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K2Cr2O7 solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K2Cr2O7 solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg−1, and the dose of K2Cr2O7 was 1.25 mg·kg−1. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. Results The Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P<0.05), the PD whole tree index in the Cr(VI) group was 27.863±2.399, which was significantly higher than that in the Con group (P<0.05), and the VC intervention significantly reversed the changes of the above indexes due to Cr(VI) exposure (P<0.05). In the β diversity analysis, the principal coordinates analysis (PCoA) results showed a significant separation between the Cr(VI) group and the Con group, and after the VC intervention, there was a retraction of the separation trend and the difference was reduced. The multi-sample similarity dendrogram results showed that the control and the VC groups clustered together first, then with the VC+Cr(VI) group, and finally with the Cr(VI) group. The abundances of Bacteroidetes, Saccharibacteria, and Tenericutes in the intestine of mice in the Cr(VI) group were decreased, and the abundance of Firmicutes was increased; the abundances of Lactobacillus, Alistipes, Bacteroides, and Ruminiclostridium were also increased. Included among these, Bacteroides showed a significantly higher abundance compared to the control mice (P<0.05). Changes in the abundances of phyla and genera of the above mentioned gut microorganisms were reversed after the VC intervention. Conclusion Cr(VI) exposure can lead to intestinal damage and disorganization of the intestinal flora structure in mice, while VC intervention can ameliorate the above changes to a certain extent and normalize the intestinal flora structure.
3.Effect of Dihuang Yinzi Decoction (地黄饮子)on Retinal Insulin Content and Insulin Signaling Pathway Related Protein Expression in Alzheimer's Disease Model Mice
Dongyan WU ; Wanwei GUI ; Xiaodan WANG ; Qinqing LI ; Jinmiao CHAI ; Junlong ZHANG
Journal of Traditional Chinese Medicine 2024;65(15):1593-1601
ObjectiveTo observe the possible mechanism of Dihuang Yinzi Decoction (地黄饮子) for improving cognitive dysfunction in Alzheimer's disease (AD) from the perspective of retina. MethodsForty-five APP/PS1 mice (AD model mice) were randomly divided into model group, Dihuang Yinzi Decoction group, and memantine group, with 15 mice in each group, while 15 wild-type C57BL/6J mice from the same litter were used as blank group. Mice in Dihuang Yinzi Decoction group were given Dihuang Yinzi Decoction 30.03 g/(kg·d) by gavage, mice in the memantine group were given memantine hydrochloride 6.1 mg/(kg·d) by gavage, and mice in the blank group and the model group were given normal saline 2 ml/(kg·d) by gavage for 4 consecutive weeks. Fasting blood glucose was measured weekly. After 4 weeks of intervention, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed; Morris water maze was used to detect the changes in spatial memory ability of mice; glucose oxidase method was used to detect retinal glucose content of mice; enzyme-linked immunosorbent assay (ELISA) was used to detect serum and retinal insulin content of mice, and Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the retina, and the retinal thickness and ganglion cell number were counted; protein immunoblotting was performed to detect the retinal pathway-associated proteins [insulin receptor substrate 1 (IRS1), phosphorylated insulin receptor substrate 1 (pIRS1), phosphatidylinositol-3-hydroxykinase (PI3K), protein kinase B (Akt1), phosphorylated protein kinase B (pAkt1)] expression; retinal glucose transporter protein 4 (GLUT4) expression was detected by immunohistochemistry. ResultsCompared with the blank group, fasting blood glucose of mice in the model group at weeks 1, 2, 3, and 4, blood glucose and area under the curve (AUC) at different time point of OGTT and ITT test, fasting serum insulin, and HOMA-IR increased (P<0.05, P<0.01); in the Morris water maze experiment, the escape latency increased from day 3 to day 5, and the number of crossing platforms, the percentage of target quadrant distance, and the percentage of target quadrant time decreased (P<0.05, P<0.01); the outer nuclear layer of the retina became sparse, thinner, and the number of ganglion cells decreases (P<0.01); the expression level of retinal glucose increased, while the expression levels of insulin, pIRS1/IRS1, PI3K/β-Actin, pAkt1/Akt1, and GLUT4 proteins decreased (P<0.01). Compared with the model group, fasting blood glucose at week 4, blood glucose at each time point of the OGTT and ITT tests AUC decreased (P<0.05, P<0.01), and fasting serum insulin and HOMA-IR decreased (P<0.05) in Dihuang Yinzi Decoction group; In the Morris water maze test, the escape latency shortened on day 4 and day 5, number of platform crossings, target quadrant distance as a proportion of total distance, and target quadrant movement time as a proportion of total time decreased (P<0.05, P<0.01); retinal pathological changes alleviated, and retinal thickness and ganglion cell number increased (P<0.01); retinal glucose content decreased, and retinal pIRS1/IRS1, PI3K/β-Actin, and GLUT4 protein expression elevated (P<0.05 or P<0.01). ConclusionsDihuang Yinzi Decoction can improve cognitive dysfunction of Alzheimer's disease, which may be related to regulating retinal insulin content and insulin signaling pathway.
4.Assessment of demand for rehabilitation services and analysis of causes of the gap between supply and demand in China
Yiran WANG ; Wanwei DAI ; Binbin SU ; Huiyun FAN ; Jianjun LI ; Xiaoying ZHENG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(6):725-729
ObjectiveTo evaluate the overall demand for rehabilitation services from the perspective of the groups with disabilities, diseases, injuries and older adults, and explore the causes of the supply and demand gap of rehabilitation services. MethodsThe literatures in the field of rehabilitation were collected, summarized and analyzed, including policy documents issued by World Health Organization and relevant departments in China, surveys, and researches. ResultsThe demand for rehabilitation services caused by disabilities, chronic diseases, injuries and population ageing were vast in China, but many were still unmet. The main reasons leading to the gap included those population trend and health situation, the insufficient reserve of rehabilitation resources coming from incomplete development of rehabilitation service system early, and inadequate construction of disability reporting system, which could not efficiently meet rehabilitation demand with supply. ConclusionThe strategies to optimize the rehabilitation services system and promote the quality of the services based on the disability reporting system are warranted.
5.Effect of sarcopenia on survival and toxicity in postoperative recurrent esophageal squamous cell carcinoma patients receiving chemoradiotherapy
Xilei ZHOU ; Changhua YU ; Weiguo ZHU ; Wanwei WANG ; Shuiqing HU ; Fuzhi JI ; Yaozu XIONG ; Yusuo TONG
Chinese Journal of Radiation Oncology 2022;31(9):785-790
Objective:To evaluate the impact of sarcopenia on survival and treatment-related toxicity in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy.Methods:Clinical data of 147 patients with postoperative locoregional recurrent ESCC receiving chemoradiotherapy in Huai'an First People's Hospital from 2016 to 2017 were retrospectively analyzed. Pectoralis muscle area (PMA) was determined using routine pre-radiotherapy CT simulation scan above the aortic arch level. Sarcopenia was defined as a cut-off value of pectoralis muscle index (PMI) (PMA/height 2) <11.55 cm 2/m 2 for males and <8.69 cm 2/m 2 for females. The incidence of toxicity, 1- and 3-year overall survival (OS) rates were statistically compared between patients with and without sarcopenia. Results:Sarcopenia was detected in 49 of 147 (33.3%) patients. The incidence of grade 3-4 toxicities in sarcopenic patients was significantly higher compared to that in their counterparts without sarcopenia (40.8% vs. 18.4%, P=0.005). In addition, patients with sarcopenia had significantly worse 1-year (61.2% vs. 82.7%) and 3-year OS rates (10.2% vs. 28.6%) than those without sarcopenia (both , P<0.001). Multivariate analysis showed that sarcopenia was an independent prognostic factor for poor OS ( P<0.001). Conclusion:PMI based on CT simulation scan has prognostic value in postoperative locoregional recurrent ESCC patients treated with chemoradiotherapy, which probably serves as a novel diagnostic tool for sarcopenia.
6.Effect of HBsAg on the production of interferon-α in peripheral blood plasmacytoid dendritic cells induced by the stimulator of interferon genes signaling pathway
Wanwei DU ; Jian GENG ; Yifan YANG ; Xia WANG ; Juanjuan FU ; Xiucheng PAN
Journal of Clinical Hepatology 2021;37(6):1295-1298
ObjectiveTo investigate the effect of HBsAg on the expression of interferon-α (IFN-α) in peripheral blood plasmacytoid dendritic cells (pDCs) induced by the stimulator of interferon genes (STING) signaling pathway activated by cyclic GMP-AMP (cGAMP). MethodPeripheral venous blood was collected from healthy adults and the patients with chronic hepatitis B virus (HBV) infection who attended the outpatient service or were hospitalized in Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, from February to December 2016, and peripheral blood mononuclear cells (PBMCs) were isolated and extracted. After the STING agonist cGAMP was added to PBMCs, ELISA was used to measure the levels of IFN-α, interferon-β, and tumor necrosis factor-α in supernatant. PBMCs from healthy adults were pre-incubated with HBsAg and then stimulated by cGAMP, and supernatant was collected to measure IFN-α. The magnetic-activated cell sorting method was used to remove pDCs from PBMCs, and after culture with cGAMP, ELISA was used to measure the level of IFN-α in supernatant. PBMCs from healthy adults were stimulated by HBsAg and/or cGAMP, and then flow cytometry was used to measure the frequency of pDCs. The independent samples t-test was used for comparison of continuous data between two groups. ResultsPBMCs from the patients with chronic HBV infection stimulated by cGAMP in vitro had a significantly lower level of IFN-α than healthy controls (469.72±18.95 vs 599.90±84.06, t=4.868, P=0.001). PBMCs from healthy adults co-cultured with HBsAg and stimulated by cGAMP had a significantly lower level of IFN-α than those in the non-HBsAg group (448.5±52.0 vs 571.0±30.8, t=4.500, P=0.011). Compared with PBMCs containing pDCs, PBMCs without pDCs stimulated by cGAMP had a significant reduction in the level of IFN-α (164.50±40.73 vs 339.50±35.33, t=6.482, P=0.001). Compared with PBMCs from healthy adults stimulated by cGAMP, PBMCs pre-incubated with HBsAg and then stimulated by cGAMP had a significant reduction in the frequency of pDCs (0.12%±0.04% vs 0.24%±0.04%, t=5.176, P=0.014). ConclusionHBsAg can inhibit the expression of IFN-α induced by the STING pathway in pDCs activated by cGAMP.
7.Clinical effect of flurbiprofen axetil in the postoperative analgesia of cervical cancer surgery
Qinghui WANG ; Yue SUN ; Wanwei JIANG
Practical Oncology Journal 2018;32(1):33-37
Objective The objective of this study was to investigate the analgesic effect of flurbiprofen axetil and its effect on immune factors after cervical cancer surgery.Methods Ninety patients with cervical cancer undergoing laparoscopic surgery were ran-domly divided into three groups with 30 patients in each group in Zhongshan Hospital Affiliated to Dalian University from January 2016 to June 2017.The indexes of assessment were visual assessment of visual analog scale(VAS)pain assessment and postoperative adverse reaction at 2,12,24 and 48 h after operation.The levels of CD4,CD8,IL-1,IL-6,CD4/CD8 and PGEs in the serum at 12,24 and 48 h after operation were measured.Results The VAS scores in the A group were significantly lower than those in the B and C groups dur-ing 12 and 24 h after operation(P<0.05).But there were no significant differences in the levels of CD4,CD8,IL-1,IL-6,CD4/CD8 and PGEs amongst the three groups(P>0.05).The levels of IL-1 and IL-6 at 2,12 and 24 h after operation were significantly higher than those in the baseline(P<0.05).However,the levels of IL-1 and IL-6 in the C group was significantly higher than those in the A and B groups(P<0.05).Compared to before operation,the ratio of CD4/CD8 was decreased and the level of PGE2 was increased in the three groups after operation.After 24 h operation,the ratio of CD4/CD8 in the B group were significantly lower than that in the C group(P<0.05).The level of PGE2 at 12 h after operation was significantly increased in the B and C groups(P<0.05).Conclusion The combination of flurbiprofen axetil and sufentanil in the laparoscopic surgery of cervical cancer can improve postoperative analgesia and reduce adverse reactions,effectively reduce the secretion of inflammatory mediators and minor affect on cellular immune function.
8.Clinical value of water exchange colonoscopy
Wanwei LIU ; Xiaoguang ZHANG ; Zefeng ZHANG ; Qiyi WANG ; Weimin LIANG ; Weihong SHA
Chinese Journal of Digestive Endoscopy 2016;33(12):860-862
Objective To compare sedated water exchange and conventional colonoscopy in the recovery time,rates of reaching ileocecal valve and adenoma detection.Methods A total of 200 newly diagnosed patients undergoing colonoscopy with routine bowel preparation and propofol intravenous anesthesia were randomly divided into 2 groups:water exchange group (WE) and conventional group,100 patients in each group.The operations were performed by two experienced physicians.The recovery time,rates of reaching ileocecal valve and adenoma detection of each group were analyzed and compared after operation.Results The recovery times of patients in water exchange and conventional groups were 8.08±0.58 min and 12.34±0.72 min,respectively (F =2 147.33,P< 0.05).Rates of reaching ileocecal valve were 100.00%(100/100,WE group) and 96.00% (96/100,conventional group),respectively(x2 =4.17,P<0.05).Adenoma detection rates of whole colon were 43.00% (43/100,WE group) and 29.00% (29/100,conventional group) (x2=4.25,P<0.05),of which small adenomas (< 1.0 cm) accounted for 83.96% (89/106,WE group) and 70.59% (48/68,conventional group) (x2 =4.43,P < 0.05),respectively.Adenoma detection rates of proximal colon were 28.00% (28/100,WE group) and 20.00% (20/100,conventional group) (x2 =1.75,P> 0.05),of which small adenomas (< 1.0 cm) accounted for 90.41% (66/73,WE group) and 74.47% (35/47,conventional group) (x2 =5.45,P < 0.05),respectively.Conclusion Water exchange colonoscopy can not only shorten the recovery time of patients,but also increase rates of reaching ileocecal valve and adenoma detection.
9.Predictive value of imaging evaluation in stage Ⅱ/Ⅲ esophageal carcinoma patients treated with preoperative chemoradiotherapy
Sheng ZHONG ; Qingquan WU ; Wanwei WANG ; Guangzhou TAO ; Jin PENG ; Weiguo ZHU
Chinese Journal of Radiological Medicine and Protection 2015;35(4):270-273
Objective Retrospectively analyzed the predictive value of imaging evaluation in stage Ⅱ/Ⅲ esophageal carcinoma patients treated with preoperative chemoradiotherapy.Methods A total of 145 stage Ⅱ/Ⅲ esophageal carcinoma pantients were enrolled.We analyzed the overall survival rates of the patients with pathological complete response (pCR) and those without (NpCR),X-film complete response (xCR) and those without (NxCR),RECIST complete response (rCR) and those without (NrCR).And we used Cox model for multivariate analysis.Results The rates of pCR,xCR and rCR were 33.8%,42.8% and 38.6% for all patients,respectively.The 1-,3-5-year overall survival rates were 87.8%,79.6%,61.2% for pCR patients and 75%,40.6%,24.0% for NpCR patients (x2 =20.215,P <0.05),respectively;The 1-,3-5-year overall survival rates were 80.6%,66.1%,51.6% for xCR patients and 75%,44.6%,25.3% for NxCR patients(x2 =8.895,P <0.05),respectively;The 1-,3-5-year overall survival rates were 83.9%,69.6%,53.6% for rCR patients and 76.4%,46.1%,25.8% for NxCR patients(x2 =10.862,P < 0.05),respectively.Multivariate survival analysis using Cox regression model showed that pCR was a positive independent prognostic factor (HR =0.333,95% CI:0.200-0.554,P < 0.05).Conclusions Short-term imaging evaluation could effectively predict the prognosis of stage Ⅱ/Ⅲ esophageal carcinoma patients treated with preoperative chemoradiotherapy.And pCR was a positive independent prognostic factor.
10.Bone marrow mesenchymal stem cell conditioned medium with hypoxic activation enhances its effects on radiation-induced intestinal epithelial cell injuryin vitro
Yuei ZHENG ; Hao CHEN ; Weihong SHA ; Qiyi WANG ; Wanwei LIU
Chinese Journal of Tissue Engineering Research 2015;(45):7230-7236
BACKGROUND:Conditioned medium from mesenchymal stem cels (MSC-CM) that contains abundant MSCs paracrine substances may represent a promising alternative to MSCs transplantation. However, normal MSC-CM with insufficient paracrine ability is not effective for tissue damage repair. OBJECTIVE:To investigate the effects of MSC-CM with (MSC-CMHyp) and without hypoxic activation (MSC-CMNor) on the proliferation and apoptosis of radiation-induced injured intestinal epithelial cels (IEC-6) and to further discuss the paracrine mechanisms. METHODS: IEC-6 cels were exposed to 10 Gy irradiation and cultured in MSC-CMHyp, MSC-CMNor, and DMEM-F12 medium, respectively. RESULTS AND CONCLUSION: Findings from trypan blue staining, flow cytometry and western blot assay showed that, compared with the DMEM-F12 medium group, treatment with MSC-CMHyp significantly enhanced IEC-6 viability proliferation after radiation-induced injury, as wel as significantly decreased cel apoptosis and expression of Caspases-3/8 (P < 0.05). However, there was no significant difference between the MSC-CMNor group and DMEM-F12 medium group (P > 0.05). On the other hand, the increased levels of vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-1, and interleukin-10 were detected in the MSC-CMHyp group compared to the MSC-CMNor group (P < 0.05). These results suggest that the MSC-CMHyp improves the viability and proliferative capacity of IEC-6 cels after radiation-induced injuryvia up-regulating secretion of cytokines and down-regulating apoptotic signaling.

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