1.The role of high mobility group box 1 in the injury of Caco-2 epithelial barrier induced by lipopolysaccharide
Xiaolei CHEN ; Siru CHEN ; Guanghui XIU ; Xianzhong CHEN ; Jie SUN ; Bin LING ; Ping LIU
Chinese Journal of Emergency Medicine 2021;30(3):287-292
Objective:To investigate the role and mechanism of high mobility group box 1(HMGB1) in the injury of Caco-2 intestinal epithelial barrier induced by lipopolysaccharide (LPS).Methods:The Caco-2 cellular monolayer barrier was established with Transwell chamber. After the Caco-2 monolayer model was established, the transepithelial electrical resistance (TEER) values were measured. When the TEER value reached 500 Ω·cm 2, the cells were divided into 3 groups: control group, LPS treatment group, and LPS+ ethyl pyruvate (EP) treatment group. The concentration of LPS and EP were 100 μg/mL, 50 μg/mL, separately. Then TEER values were measured at 12, 24, 48 and 72 h, and FITC-dextran permeability was detected at 24 h. The cells were seeded on 6-well plates. After cell density reached 80%, treatments were given as the above. The real-time polymerase chain reaction (RT-PCR) and Western blot were used to measure the changes in the protein and mRNA expressions of Occludin, HMGB1, and nuclear factor-κB (NF-κB). Results:Compared with the control group, the TEER values (Ω·cm 2) reduced at 12, 24, 48 and 72 h in the LPS treatment group [(514.22±12.59) vs (304.96±9.69), (521.65±13.35) vs (276.21±7.82), (523.99±8.18) vs (206.64±15.85), (491.21±6.72) vs (156.33±10.83), all P<0.05]. The FITC-dextran permeability increased significantly at 24 h [(2.58±0.07) vs (1.04±0.06), P<0.05]. The expression levels of Occludin protein and mRNA were decreased (all P<0.05), while the expression levels of HMGB1 and NF-κB protein and mRNA were significantly increased (all P<0.05). Compared with the LPS treatment group, the TEER values (Ω·cm 2) increased significantly at 12, 24, 48 and 72 h in the EP treatment group [(519.00±5.66) vs (304.96±9.69), (504.69±8.57) vs (276.21±7.82), (453.65±10.74) vs (206.64±15.85), (385.28±7.57) vs (156.33±10.83), all P<0.05]. The FITC-dextran permeability decreased at 24 h [(1.23±0.11) vs (2.58±0.07), P<0.05]. The expression level of Occludin protein and mRNA were increased ( P<0.05), while the expression levels of HMGB1 and NF-κB protein and mRNA were significantly decreased (all P<0.05). Conclusions:LPS can injure intestinal barrier directly in vitro and reduces the expression of tight junction proteins between cells. The mechanism may be related to the increased expression of HMGB1 and NF-κB protein.
2.Effect of ovariectomy on cognitive function and hippocampal estrogen receptor expression in APP/PS1 mice
Chao CONG ; Zuxi GU ; Panqing WU ; Siru CHEN ; Guangyao LIN ; Lianwei XU
Chinese Journal of Comparative Medicine 2024;34(10):1-9
Objective The present study aimed to observe the changes in Aβ deposition and estrogen receptor levels in the hippocampal tissue of female APP/PS1 mice with Alzheimer's disease(AD)after receiving an ovariectomy at different ages.Methods 3-month-old APP/PS1 female mice were divided into three groups,with 20 mice in each group.Ten mice were treated with bilateral ovarian resection via abdominal surgery as the model(ovx)group.The 10 mice in the control(sham)group underwent surgery in which an equivalent volume fat was removed from the corresponding area.After 3,4,and 5 months,APP/PS1 mice were assigned to 6-,7-,and 8-month age groups.The cognitive function of the APP/PS1 mice of different ages was evaluated using the Morris water maze.Morphological changes to intracellular organelles in the CA1 area of the hippocampus of the two groups of mice were observed using transmission electron microscopy.Immunofluorescence staining was used to detect the deposition of Aβ in the CA1 area of the hippocampus of the two groups of mice.ELISA was used to detect the levels and contents of serum estrogen,ROS,SOD,and MDA,and Western blot was used to determine the expression levels of ERα and ERβ.Results As the ovx group mice increased in age,their escape latency in the water maze test gradually lengthened,the deposition of Aβ in the hippocampal CA1 area increased,the mitochondrial swelling of hippocampal neurons increased,and larger amounts of lipofuscin and amyloid deposition were observed in the cytoplasm.Their serum E2 levels and SOD activity decreased,while their ROS levels and MDA contents increased,and the expression of ERα and ERβ in the hippocampal tissue decreased.Conclusions Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβ deposition and age-dependent cognitive decline.
3.Association between volatile organic compounds and mortality risk of stroke
Siru YANG ; Lin HUANG ; Hang DONG ; Di LIU ; Zhou YANG ; Sujuan CHEN ; Guozhen LIN ; Boguang WANG ; Jun YANG
Chinese Journal of Epidemiology 2023;44(8):1216-1223
Objective:To investigate the effect of volatile organic compounds (VOCs) exposure in the atmosphere on the risk of daily death from stroke in Guangzhou.Methods:Daily average concentrations of twelve atmospheric VOCs, meteorological factors, and daily deaths for stroke and its subtypes (including ischemic and hemorrhagic stroke) in Guangzhou from 2020 to 2021 were collected. The time-series Poisson generalized additive model was established to analyze the relationship between daily average concentrations of atmospheric VOCs and daily mortality from a stroke on different lag days. The season, gender, and age group further performed stratification analysis.Results:Toluene and n-pentane were associated with a higher mortality risk from stroke and its subtypes. For each interquartile range ( IQR) increment in toluene concentration at lag0- 1 days, the RRs for mortality from stroke and hemorrhagic stroke were 1.060 (95% CI: 1.036-1.085) and 1.071 (95% CI: 1.030-1.113), respectively. For each IQR increment in n-pentane concentration, the RR for mortality from ischemic stroke was 1.064 (95% CI: 1.030-1.099). The effect estimates of VOCs may be higher during the cold season and among women and people aged ≥75 years. For each IQR increment in toluene concentration, the RRs for mortality risk of stroke in the cold season and women were 1.099 (95% CI: 1.056-1.143) and 1.085 (95% CI: 1.050-1.120), respectively. For n-pentane, the RR for death risk of stroke in people aged ≥75 years old was 1.072 (95% CI: 1.036-1.109). Results of sensitivity analysis showed that the effect estimates fluctuated less when PM 2.5 and O 3 were separately introduced for the two-pollutant model, as well as changing the degrees of freedom for covariates. Conclusions:This study suggests that VOCs may be an independent risk factor for daily mortality from stroke. Moreover, Toluene presented the most significant health impact.
4.Role of high mobility group box 1 in intestinal mucosal barrier injury in rat with sepsis induced by endotoxin
Siru CHEN ; Guanghui XIU ; Juan ZHOU ; Ping LIU ; Xianzhong CHEN ; Jie SUN ; Bin LING
Chinese Critical Care Medicine 2020;32(7):803-807
Objective:To investigate the role and mechanism of the high mobility group box 1 (HMGB1) in intestinal mucosal barrier injury in rat with sepsis induced by endotoxin lipopolysaccharide (LPS).Methods:The rats were given intraperitoneal injection of LPS to reproduce a model of sepsis. The effect of HMGB1 inhibitor EP solution (40 mg/kg) on sepsis was observed, and phosphate buffer (PBS) control group was set up. Seventy-two hours after modeling, abdominal aortic blood was obtained, and enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma levels of D-lactic acid and diamine oxidase (DAO) of mucosal barrier permeability. The pathological changes of the intestinal mucosal were observed with light microscope and the Chiu score was recorded. The intestinal mucosal ultrastructural changes were observed with electron microscopy. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot were used to measure the mRNA and protein expressions of Occludin, inflammatory factor HMGB1 and its downstream signal molecule nuclear transcription factor-κB p65 (NF-κB p65) in the rat small intestine.Results:The results of histopathology and ultrastructure of the small intestine showed that in the LPS group, the intestinal mucosa tissue swelled obviously, part of the glands were incomplete, the infiltration of neutrophils increased, themicrovillus cells were absent, arranged indisorder, and the number of tight connections significantly reduced compared with the PBS control group. The levels of D-lactic acid and DAO indicating mucosal barrier permeability, the levels of inflammatory factor HMGB1 and its downstream signaling molecule NF-κB p65 mRNA and protein expressions in the LPS group were significantly higher than those in the PBS control group, and the mRNA and protein expression of Occludin in the small intestine was significantly lower than that in the PBS control group, suggesting that the intestinal mucosal barrier function in septic rats was damaged, permeability increased, and the structure was damaged. After the administration of the HMGB1 inhibitor EP, the intestinal mucosal barrier damage was significantly improved. The performance was as follows: the Chiu score of the small intestine tissue and the plasma D-lactic acid and DAO levels in the EP intervene group were significantly lower than those in the LPS group [Chiu score: 1.60±0.48 vs. 3.40±0.48, D-lactic acid (mmol/L): 3.30±0.22 vs. 5.30±0.16, DAO (U/L): 23.66±0.97 vs. 30.47±1.11, all P < 0.05]. Occludin mRNA and protein expression levels were significantly higher than those in the LPS group [Occludin mRNA (2 -ΔΔCt): 0.82±0.05 vs. 0.37±0.08, Occludin protein (Occludin/β-actin): 1.04±0.09 vs. 0.75±0.11, both P < 0.05], while the mRNA and protein expression levels of HMGB1 and NF-κB p65 were significantly lower than those in the LPS group [HMGB1 mRNA (2 -ΔΔCt): 1.63±0.10 vs. 3.57±0.10, HMGB1 protein (HMGB1/β-actin): 1.40±0.07 vs. 1.87±0.07; NF-κB p65 mRNA (2 -ΔΔCt): 1.47±0.09 vs. 2.62±0.13, NF-κB p65 protein (NF-κB p65/β-actin): 1.24±0.14 vs. 1.60±0.13, all P < 0.05]. Conclusions:Intestinal mucosal barrier function of septic rats was damaged, permeability increased, and structure was damaged. The mechanism may be that the expression of inflammatory factor HMGB1 was up-regulated and promoted the activation of its downstream signaling molecule NF-κB, thereby mediated the inflammatory cascade reaction and caused damage to the intestinal mucosa.
5.A novel draw-bar skin stretcher for repair of full-thickness skin defects
Yuzhuo HAN ; Yonghua CHEN ; Dong LIU ; Qingshan GUO ; Siheng DU ; Siru ZHOU ; Lianyang ZHANG ; Yang LI
Chinese Journal of Orthopaedic Trauma 2021;23(7):627-631
Objective:To evaluate a new type of draw-bar skin stretcher in repair of full-thickness skin defects.Methods:From May 2015 to January 2019, 52 patients with full-thickness skin defects were repaired with a new type of draw-bar skin stretcher at Daping Hospital, Army Medical University. They were 40 males and 12 females, aged from 4 to 61 years (average, 37.1 years). Their skin was stretched for primary wound closure. When primary wound closure failed, skin stretching was performed again to close the wound depending on the wound condition. When the Pinch test was negative after skin stretching, the wound was sutured directly. In cases of positive Pinch test, a skin graft or flap was used to repair the remaining wound. At 12 months after surgery, scar contracture and size of skin graft or flap were observed and wound healing after skin stretching was evaluated in comparison with the original wound.Results:After skin stretching, one-stage wound closure was achieved in 36 cases and multi-stage wound closure in 8 cases; of the remaining 8 cases, 2 were repaired by skin graft and 6 by skin flap after their wounds were reduced by skin stretching. In one-stage closed wounds, infection occurred in 3 cases and marginal necrosis in 5 cases; in the wounds repaired by skin graft or flap, no infection or necrosis was observed. The 12-month follow-up for all the patients showed fine healing of all the wounds after one-stage or multi-stage closure, linear scar, absence of scar contracture, and smaller wound sizes than the original ones after skin graft or flap repair.Conclusions:Skin stretching using our new type of draw-bar skin stretcher is an effective treatment for skin wounds. It can replace traditional skin grafting and flap surgery in some cases, but its indications should be strictly followed to avoid related complications.
6. Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel coronavirus pneumonia
Yang LI ; Zhanfei LI ; Qingxiang MAO ; Ding LIU ; Letian ZHANG ; Fan YANG ; Yu XIE ; Siru ZHOU ; Huayu ZHANG ; Shanmu AI ; Hao TANG ; Qiu ZHONG ; Qingshan GUO ; Yaoli WANG ; Weiguo ZHANG ; Liyong CHEN ; Xiangjun BAI ; Lianyang ZHANG
Chinese Journal of Trauma 2020;36(2):1-7
A novel coronavirus pneumonia (NCP) epidemic has occurred in Wuhan, Hubei Province since December 2019, caused by a novel coronavirus (2019-nCoV) never been seen previously in human. China has imposed the strictest quarantine and closed management measures in history to control the spreading of the disease. However, severe trauma can still occur in the NCP patients. In order to standardize the emergency treatment and the infection prevention and control of severe trauma patients with hidden infection, suspected or confirmed infection of 2019-nCoV, Trauma Surgery Branch of Chinese Medical Doctors' Association organized this expert consensus. The consensus illustrated the classification of the NCP patients, severe trauma patients in need of emergency surgery, emergency surgery type, hierarchical protection for medical personnel and treatment places. Meanwhile, the consensus standardized the screening, injury severity evaluation, emergency surgical treatment strategy and postoperative management strategy of severe trauma patients during the epidemic period of NCP, providing a basis for the clinical treatment of such kind of patients.