1.Establishment of a dynamic model of acute lung injury in mice based on the NLRP3/Caspase-1/gasdermin D signaling pyroptosis pathway
Yixuan FAN ; Xinwei WANG ; Junmei LI ; Liang YI ; Zhixu YANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):423-434
Objective To establish a dynamic model of lipopolysaccharide-induced acute lung injury in mice based on the NLRP3/Caspase-1/gasdermin D(GSDMD)pyroptosis pathway,and observe the result ing lung injury at different time points.We aimed to identify the optimal time for modelling according to the injury at different time points and the expression of pyroptosis pathway-related proteins,to lay the foundation for animal models for subsequent experiments.Methods Fifty-four 6~8 weeks old male SPF BALB/c mice were divided randomly into nine groups,including Con group and model groups at 1,3,6,12,18,24,48,and 72 h.Body weight and lung tissue were detected by general and pathological observations and semi-quantitative scoring,including lung index,lung water content,and wet and dry weight ratio.The white blood cell count and concentrations of tumor necrosis factor-α,interleukin(IL)-6,IL-1β,IL-18,and BCA protein were detected in bronchoalveolar lavage fluid(BALF).The classic pyroptosis pathway-related proteins NLRP3,pro-Caspase 1,Caspase 1,and GSDMD were detected by Western Blot.Results Body weight decreased in all experimental groups,with the most significant weight loss in the 24 and 48 h groups.Gross observation and pathological examination of lung tissue showed that the most severe lung injury occurred at 24~72 h,with significant differences between each group and the control group.The lung index,lung water content,and wet/dry weight ratio were also significantly increased at 24~72 h.White blood cells in BALF started to increase from 6 h after model initiation,48 h can reach a peak,72 h all keep increasing.IL-18 in BALF began to increase at 24 h and continued to increase at 72 h.The inflammatory factors tumor necrosis factor-α,IL-1β,IL-6 were highest at 6 h and significantly reduced at 48 h.Protein concentrations in BALF were significantly increased within 24,48,and 72 h compared with those in the control group.The pyroptosis pathway proteins NLRP3,pro-Caspase-1,Caspase-1,and GSDMD were significantly enhanced in each time series,and channel protein expression was significantly enhanced at 24~72 h compared with that in the Con group.Conclusions Comprehensive analysis of experimental indicators,inflammatory factors,and pathway proteins at different times showed that the mechanism of pyroptosis was closely related to the occurrence and progression of acute lung injury.Expression of the pyroptosis pathway was most obvious and lung injury was most serious at 24~48 h.This study provides a model reference and experimental basis for subsequent studies of the specific mechanism and intervention targets of acute lung injury.
2.Analysis of monitoring results of novel coronavirus IgM and IgG antibody levels in apheresis platelets donors and impact on blood safety
Hui ZHANG ; Xinwei WANG ; Ruru HE ; Zhenxing WEI ; Jinheng LIANG ; Dong PANG ; Limin CHEN
Chinese Journal of Blood Transfusion 2023;36(9):770-774
【Objective】 To monitor the positive rates of IgM and IgG antibodies and the changes in S/CO values over time in voluntary blood donors infected with SARS-CoV-2 after recovery, in order to provide theoretical basis and data support for ensuring clinical blood safety. 【Methods】 A total of 54 platelet donors who met the inclusion criteria were selected for this study, and 359 blood samples (plasma) from T
3.Correction of lateral type alar retraction with lateral crural strut graft and intercartilaginous graft
Zhiwei LIANG ; Fanglin ZENG ; Huhu YANG ; Xinwei WANG
Chinese Journal of Plastic Surgery 2022;38(7):744-748
Objective:To explore the surgical method and clinical effect of correcting lateral type alar retraction with intercartilaginous graft and lateral crural strut graft.Methods:A retrospective study was performed on the data of patients with moderate to severe lateral alar retraction treated in Shenzhen Mylike Medical Plastic Aesthetic Hospital from October 2018 to June 2020. During the operation, lower lateral cartilages was totally dissected and strengthened by lateral crural strut graft while scroll area was released and lengthened with intercartilaginous graft to correct lateral type alar retraction. The preoperative and postoperative distance from the nostril’s long axis to the alar rim was measured from the side view, the nasal measurements were expressed as Mean±SD, and paired t-test was used for statistical analysis. Results:A total of 32 patients were enrolled, including 5 males and 27 females, with an average age of 31 years (18-47 years). Twenty-three cases underwent primary rhinoplasty and 9 cases underwent second rhinoplasty. The preoperative data of distance from the nostril’s long axis to the alar rim was (4.1±0.5) mm (3.2-5.0 mm). The postoperative effect of nasal alar retraction defomity correction was obvious. After a follow-up period of 20 cases from 6 to 18 months, the distance from the nostril’s long axis to the alar rim was 1.5-2.8 mm [(2.1±0.3) mm on average]. Comparison of preoperative and postoperative measured values showed statistically significant difference ( P<0.01). There was 1 patient emerged complication alar flaring, and no contracture and deformation of the nasal rim occurred. All of patients were satisfied. Conclusions:The intercartilaginous graft combined with lateral crural strut graft is an effective new method for correction of lateral type alar retraction. It has stable clinical effect and high satisfaction.
4.Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (version 2022)
Zhengwei XU ; Dingjun HAO ; Liming CHENG ; Baorong HE ; Bohua CHEN ; Chen CHEN ; Fei CHE ; Jian CHEN ; Qixin CHEN ; Liangjie DU ; Shunwu FAN ; Zhong FANG ; Shiqing FENG ; Yanzheng GAO ; Haishan GUAN ; Zhong GUAN ; Hua JIANG ; Weimin JIANG ; Dianming JIANG ; Jun JIANG ; Yue JIANG ; Lijun HE ; Yuan HE ; Bo LI ; Tao LI ; Jianjun LI ; Xigong LI ; Yijian LIANG ; Bin LIN ; Bin LIU ; Bo LIU ; Yong LIU ; Zhibin LIU ; Xuhua LU ; Chao MA ; Lie QIAN ; Renfu QUAN ; Hongxun SANG ; Haibo SHEN ; Jun SHU ; Honghui SUN ; Tiansheng SUN ; Jun TAN ; Mingxing TANG ; Sheng TAO ; Honglin TENG ; Yun TIAN ; Jiwei TIAN ; Qiang WANG ; Xinwei WANG ; Jianhuang WU ; Peigen XIE ; Weihong XU ; Bin YAN ; Yong YANG ; Guoyong YIN ; Xiaobing YU ; Yuhong ZENG ; Guoqing ZHANG ; Xiaobo ZHANG ; Jie ZHAO ; Yue ZHU
Chinese Journal of Trauma 2022;38(11):961-972
Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.
5.Correction of lateral type alar retraction with lateral crural strut graft and intercartilaginous graft
Zhiwei LIANG ; Fanglin ZENG ; Huhu YANG ; Xinwei WANG
Chinese Journal of Plastic Surgery 2022;38(7):744-748
Objective:To explore the surgical method and clinical effect of correcting lateral type alar retraction with intercartilaginous graft and lateral crural strut graft.Methods:A retrospective study was performed on the data of patients with moderate to severe lateral alar retraction treated in Shenzhen Mylike Medical Plastic Aesthetic Hospital from October 2018 to June 2020. During the operation, lower lateral cartilages was totally dissected and strengthened by lateral crural strut graft while scroll area was released and lengthened with intercartilaginous graft to correct lateral type alar retraction. The preoperative and postoperative distance from the nostril’s long axis to the alar rim was measured from the side view, the nasal measurements were expressed as Mean±SD, and paired t-test was used for statistical analysis. Results:A total of 32 patients were enrolled, including 5 males and 27 females, with an average age of 31 years (18-47 years). Twenty-three cases underwent primary rhinoplasty and 9 cases underwent second rhinoplasty. The preoperative data of distance from the nostril’s long axis to the alar rim was (4.1±0.5) mm (3.2-5.0 mm). The postoperative effect of nasal alar retraction defomity correction was obvious. After a follow-up period of 20 cases from 6 to 18 months, the distance from the nostril’s long axis to the alar rim was 1.5-2.8 mm [(2.1±0.3) mm on average]. Comparison of preoperative and postoperative measured values showed statistically significant difference ( P<0.01). There was 1 patient emerged complication alar flaring, and no contracture and deformation of the nasal rim occurred. All of patients were satisfied. Conclusions:The intercartilaginous graft combined with lateral crural strut graft is an effective new method for correction of lateral type alar retraction. It has stable clinical effect and high satisfaction.
6.Matrix metalloproteinase regulates natural killer cells function in methicilin-resistant staphylococcus aureus sepsis
Haijun LIANG ; Yanhui CUI ; Yanping WANG ; Xinwei WANG ; Haili GAO ; Baoxin CHEN ; Daokun YANG
Chinese Journal of Emergency Medicine 2020;29(6):835-840
Objective:To investigate the characteristics of natural killer (NK) cell subsets and function in methicillin-resistant staphylococcus aureus (MRSA) sepsis, and to assess the influence of matrix metalloproteinase (MMP) to NK cell function in MRSA sepsis patients.Methods:Twenty-one MRSA sepsis patients who were hospitalized in our department between January 2017 and June 2018 were enrolled. Eleven healthy individuals were served as healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated. NK cell subsets were investigated by flow cytometry. NK cell function was assessed by measuring CD107a, CD69, and CD16 expression in co-culture system between PBMCs and different target cells. MMP mRNA was semi-quantified by real-time PCR in purified NK cells. The influence of NK cell function was assessed by measuring CD107a expression in co-culture system between NK cells with MMP inhibitor stimulation and target cells.Results:There was no significant difference of total NK cell percentage between healthy controls and MRSA sepsis patients ( P>0.05). CD56brightCD16 -NK [(5.36±1.02)% vs (4.30±0.89)%] and CD56 -CD16 +NK [(24.04±2.92)% vs (9.70±1.54)%] percentage was elevated ( P<0.05), while CD56dimCD16 +NK percentage [(71.22±13.03)% vs (87.64±7.05)%, P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% vs(18.80±1.49)%] was decreased ( P<0.0001), while CD16 MFI was increased [(247.1±50.31) vs (189.4±57.54), P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients ( P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% vs (25.87±6.23)%, P=0.018]. Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.
7.Hypernatremia increases the incidence of late delirium after cardiac surgery
Liang HONG ; Xiao SHEN ; Chang SHU ; Qiankun SHI ; Xinwei MU ; Cui ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(11):1320-1325
Objective To analyze whether hypernatremia within 48 hours after cardiac surgery will increase the incidence of delirium which developed 48 hours later after surgery (late-onset delirium). Methods We conducted a retrospective analysis of 3 365 patients, including 1 918 males and 1 447 females, aged 18-94 ( 60.53±11.50) years, who were admitted to the Department of Cardiothoracic and Vascular Surgery of Nanjing First Hospital and underwent cardiac surgery from May 2016 to May 2019. Results A total of 155 patients developed late-onset delirium, accounting for 4.61%. The incidence of late-onset delirium in patients with hypernatremia was 9.77%, the incidence of late onset delirium in patients without hypernatremia was 3.45%, and the difference was statistically different (P<0.001). The odds ratio (OR) of hypernatremia was 3.028 (95% confidence interval: 2.155-4.224, P<0.001). The OR adjusted for other risk factors including elderly patients, previous history of cerebrovascular disease, operation time, cardiopulmonary bypass time, lactate, hemoglobin≥100 g/L, prolonged mechanical ventilation, left ventricular systolic function, use of epinephrine, use of norepinephrine was 1.524 (95% confidence interval: 1.031-2.231, P=0.032). Conclusion Hypernatremia within 48 hours after cardiac surgery may increase the risk of delirium in later stages.
8.Therapeutic effect of mild hypothermia on the inflammatory response and outcome in perioperative patients with acute Stanford type A aortic dissection: A randomized controlled trial
ZOU Lei ; ZHANG Cui ; SONG Xiaochun ; FU Run ; SHEN Xiao ; HONG Liang ; MU Xinwei ; HUANG Fuhua ; XIAO Liqiong
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2019;26(3):222-228
Objective To explore the therapeutic effect of mild hypothermia on the inflammatory response, organ function and outcome in perioperative patients with acute Stanford type A aortic dissection (AAAD). Methods From February 2017 to February 2018, 56 patients with AAAD admitted in our department were enrolled and randomly allocated into two groups including a control group and an experimental group. After deep hypothermia circulatory arrest during operation, in the control group (n=28), the patients were rewarmed to normal body temperatures (36 to 37 centigrade degree), and which would be maintained for 24 hours after operation. While in the experimental group (n=28), the patients were rewarmed to mild hypothermia (34 to 35 centigrade degree), and the rest steps were the same to the control group. The thoracic drainage volume and the incidence of shivering at the first 24 hours after operation, inflammatory indicators and organ function during perioperation, and outcomes were compared between the two groups. There were 20 males and 8 females at age of 51.5±8.7 years in the control group, 24 males and 4 females at age of 53.3±11.2 years in the experimental group. Results There was no obvious difference in the basic information and operation information in patients between the two groups. Compared to the control group, at the 24th hour after operation, the level of peripheral blood matrix metalloproteinases (MMPs) was lower than that in the experimental group (P=0.008). In the experimental group, after operation, the awakening time was much shorter (P=0.008), the incidence of bloodstream infection was much lower (P=0.019). While the incidence of delirium, acute kidney injury (AKI), hepatic insufficiency, mechanical ventilation duration, intensive care unit (ICU) stays, or hospital mortality rate showed no statistical difference. And at the first 24 hours after operation, there was no difference in the thoracic drainage volume between the two groups, and no patient suffered from shivering. Conclusion The mild hypothermia therapy is able to shorten the awakening time and reduce the incidence of bloodstream infection after operation in the patients with AAAD, and does not cause the increase of thoracic drainage volume or shivering.
9.Protective effect and mechanism of serum containing Euonymus fortunei on rat pancreatic islet cells
Peng JIANG ; Hongjun GAO ; Jianpeng YOU ; Taisheng LIANG ; Xinwei GU ; Jianqiang ZHANG ; Fangfang LIANG ; Fu HUANG ; Zhen WU
Organ Transplantation 2018;9(4):290-296
Objective To investigate the protective effect and mechanism of serum containing Euonymus fortunei on the rat pancreatic islet cells. Methods Forty male SD rats were randomly divided into 5 groups (n=8 in each group), including the control group (normal rat islet cells were cultured with normal rat serum), ischemic preconditioning group (abdominal aorta was blocked first and then re-opened before the pancreas was obtained, and the pancreatic islet cells were cultured with normal rat serum), Euonymus fortunei treatment group (normal rat islet cells were cultured with rat serum containing Euonymus fortunei), Euonymus fortunei group and blank group (normal rats were administered orally with Euonymus fortunei extract or distilled water for the preparation of rat serum). Diphenylthiocarbazone (DTZ) staining was utilized to observe and calculate the quantity of islets. Acridine orange (AO)/propidium iodide (PI) staining was adopted to calculate the survival rate of islet cells. The insulin release experiment was performed to calculate the stimulation index (SI) and evaluate islet cell function. The concentration of glutathione (GSH) and nitric oxide (NO) in islet cells was detected using GSH and NO kits. The expression level of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) was quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Islet cells were observed in specifically scarlet color after DTZ staining. The quantity of islet cells did not significantly differ among different groups (all P>0.05). Along with the prolongation of culture time, the activity of islet cells in each group was gradually decreased. At 72 h after isolation and culture, compared with the control group, the survival rate of the cells was significantly higher in the Euonymus fortunei treatment group (P<0.05). The insulin release test results demonstrated that compared with the control group, the SI of the ischemic preconditioning and Euonymus fortunei treatment groups was significantly increased (both P<0.05). Compared with the control group, the GSH contents of pancreatic islet cells in the ischemic preconditioning and Euonymus fortunei treatment groups were considerably enhanced, the NO content was significantly decreased, and the expression level of iNOS mRNA was significantly down-regulated (all P<0.05). Conclusions Euonymus fortunei can increase the survival rate of islet cells and enhance the function of pancreatic islets by increasing the level of GSH, down-regulating the expression of iNOS and decreasing the NO production.
10.Influences of the size of lymph node metastasis on the chemoradiotherapy efficacy and prognosis for the patients after esophagectomy of thoracic esophageal squamous cell carcinoma
Xinwei GUO ; Shengjun JI ; Shaobing ZHOU ; Liang GU ; Yangchen LIU
Journal of International Oncology 2018;45(3):148-152
Objective To evaluate the effects of the size of lymph node metastasis (LNM) on the chemoradiotherapy efficacy and prognosis for the patients after resection of thoracic esophageal squamous cell carcinoma (ESCC).Methods Between 2011 and 2014,a total of 75 esophageal squamous carcinoma patients with secondary LNM after resection of ESCC were recruited in this retrospective study.They were treated with curative radiotherapy only or concurrent chemoradiotherapy in the Affiliated Taixing People's Hospital of Yangzhou University.Thc LNM volume and maximum diameters were measured by the Monaco treatment planning system.The enrolled patients were grouped according to the median values of LNM volume and maximum diameters.The relationship between the responsiveness to treatment and these markers was analyzed by univariate and multivariate logistic analysis.The Kaplan-Meier method and Log-rank test were adopted to calculate and compare the overall survival (OS) rates with these markers.The Cox proportional hazards model was used to carry out univariate and multivariate analyses.Results The overall effective rate was 69.3% for all enrolled patients.The response rates were 81.6% with LNM volume <57 cm3 and 56.8% with LNM volume ≥57 cm3.The response rates were 83.8% with LNM maximum diameter < 5 cm and 55.3% with LNM maximum diameter ≥5 cm.The responses to treatment were highly associated with treatment method (OR =1.825,95% CI:1.134-3.658,P =0.017),LNM volume (OR =4.183,95% CI:1.416-12.354,P =0.010) and maximum diameter (OR =3.374,95% CI:1.185-9.611,P =0.023) by univariate logistic regression analysis.Multivariate logistic regression analysis showed that therapeutic method (OR =1.225,95% CI:1.085-2.837,P =0.038) and LNM volume (OR =1.614,95% CI:1.003-3.025,P =0.048) were independent risk factors for tumor response.The median OS time of this cohort was 14 months,and the 1,2 and 3 year OS rates were 60.7%,25.3% and 20.1%,respectively.Kaplan-Meier survival analysis revealed that TNM stage (HR =2.039,95 % CI:1.234-3.370,P =0.005),treatment methods (HR =1.858,95 % CI:1.385-2.958,P =0.013),LNM volume (HR =2.642,95% CI:1.552-4.497,P < 0.001) and LNM maximum diameter (HR =3.399,95 % CI:1.939-5.958,P < 0.001) were significantly associated with OS.Furthermore,multivariate Cox proportional hazard regression model analysis for OS was performed and the results showed that TNM stage (HR =2.023,95 % CI:1.149-3.560,P =0.015),LNM volume (HR =2.055,95 % CI:1.041-4.055,P =0.038) and maximum diameter (HR =1.910,95% CI:1.137-3.895,P =0.045) were considered as independent prognostic risk factors for OS.Conclusion LNM volume in ESCC patients with secondary LNM after esophagectomy has great values for predictive therapeutic effects and survival outcomes,and LNM maximum diameter has significant value for survival outcomes.


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