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Fifteen compounds were isolated from the 95% ethanol extract of the whole plant of Elephantopus tomentosus L. by silica gel column chromatography, Sephadex LH-20 column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, and spectral data (UV, IR, NMR, MS and CD) analysis as tomenlephanlide A (1), molephantinin (2), molephantin (3), 8-O-methacryloylelephanpane (4), apigenin (5), tricin (6), 2-phenyl acetamide (7), 3,4-dihydroxybenzoic acid methyl ester (8), caffeic acid methyl ester (9), caffeic acid ethyl ester (10), (+)-(4S)-(2E)-4-hydroxy-2-nonenoic acid (11), E-4-hydroxyhex-2-enoic acid (12), 1H-indole-3-carboxylic acid (13), 1H-indole-3-carbaldehyde (14) and isohematinic acid (15). Among them, compound 1 is a new germacrene-type sesquiterpenoid, 5-15 were obtained from E. tomentosus L. for the first time. It was the first time the absolute configuration of compound 2 was reported. Compound 1 showed weak cytotoxicity against gastric cancer cells (SGC-7901).
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Objective:To study the types of pathogenic gene mutations and their main clinical characteristics in children with glucose-6-phosphate dehydrogenase (G6PD) deficiency in Zunyi area.Methods:Children with clinical manifestations of "yellow staining" or "suspected yellow staining" who were admitted to Guizhou Children's Hospital, Affiliated Hospital of Zunyi Medical University, from September 13, 2018 to September 13, 2020 were selected for G6PD gene mutation detection by multicolor probe melting curve analysis, and the pathogenic gene mutation types and clinical characteristics of children with G6PD deficiency were analyzed.Results:The results of G6PD gene mutation detection showed that among the 1 740 children tested, 119 were positive for gene mutation, and the positive detection rate was 6.84%. The proportion of male infants was higher than that of female infants, and the difference was statistically significant (91 males and 28 females, χ 2 = 15.10, P < 0.001); infancy accounted for 63.87% (76/119), and early childhood accounted for 18.49% (22/119). A total of 11 known pathogenic gene mutation types and 1 unknown mutation were detected. Among the top 4 pathogenic gene mutations, the overall was c.1024 C>T, c.1376 G>T, c.1388 G>A and c.95 A>G, male was c.1376 G>T, c.1388 G>A, c.1024 C>T and c.95 A>G; female was c.1024 C>T, c.95 A>G, c.1388 G>A and c.519 C>T. Among the 119 children with G6PD gene mutation, 90 cases had varying degrees of jaundice, including 36 cases of severe and more severe jaundice (including 2 cases of extremely severe neonatal bilirubin encephalopathy), and 54 cases of mild to moderate jaundice; 37 cases had anemia of different degrees, including 6 cases of mild anemia, 12 cases of moderate anemia, and 19 cases of severe or more severe anemia (including 1 case of extremely severe anemia). Conclusions:There are 12 types of gene mutations in children with G6PD deficiency in Zunyi area, and the most common mutation types are c.1024 C>T, c.1376 G>T, c.1388 G>A and c.95 A>G. Children with G6PD deficiency are often accompanied by varying degrees of jaundice and anemia.
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Objective:To investigate the influencing factors and management strategies of colonoscopy-associated colorectal perforation.Methods:The retrospective case-control study was conducted. The clinical data of 358 patients who underwent colonoscopy in the Affiliated Hospital of Zunyi Medical University from January 2011 to March 2021 were collected. There were 216 males and 142 females, aged (59±14)years. Patients underwent colonoscopy for diagnosis or treatment. Observation indicators: (1) situations of colonoscopy-associated colorectal perforation; (2) analysis of influencing factors of colonoscopy-associated colorectal perforation; (3) construction of prediction model of colonoscop-associated colorectal perforation; (4) management of colonoscopy-associated colorectal perforation. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Wilcoxom rank sum test. Count data were discribed as absolute numbers, and comparison between groups was analyzed using the chi-square test. Multivariate ana-lysis was conducted using the binary Logistic regression model. The sensitivity and specificity of the prediction model were evaluated by the receiver operating characteristic (ROC) curve. Results:(1) Situations of colonoscopy-associated colorectal perforation. Of the 358 patients, 18 cases developed colorectal perforation, including 6 males and 12 females, with an age of 61(49,69) years. Of the 18 patients, there were 12 cases with colon perforation, including 10 cases of sigmoid colon perfora-tion or rectosigmoid junction perforation, 1 case of transverse colon perforation and 1 case of descending colon perforation, 6 cases with rectal perforation. There were 11 cases with diagnostic perforation and 7 cases with therapeutic perforation. (2) Analysis of influencing factors of colonoscopy-associated colorectal perforation. Results of univariate analysis showed that gender, age, colorectal ulcer, colorectal diverticulum, colorectal tumor, history of abdominal surgery, type of colonoscopy and the experience of operating physician were related factors for colonoscopy-associated colorectal perforation ( χ2=5.77, Z=?3.24, χ2=37.99, 97.34, 37.99, 10.31, 8.07, 6.73, P<0.05). Results of multi-variate analysis showed that colorectal diverticulum and abdominal surgery history were indepen-dent risk factors for colonoscopy-associated colorectal perforation ( odds ratios=287.79, 6.74, 95% confidence intervals as 23.14?3 579.11, 1.19?38.27, P<0.05). Therapeutic colonoscopy was an independent protective factor for colonoscopy-associated colorectal perforation ( odds ratio=0.11, 95% confidence interval as 0.23?0.52, P<0.05). (3) Construction of prediction model of colonoscopy-associated colorectal perforation. With the colonoscopy-associated colorectal perforation as depen-dent variable, colorectal diverticulum, abdominal surgery history and therapeutic colonoscopy as independent variables, a prediction model of colonoscopy-associated colorectal perforation was constructed. The ROC of model showed that the sensitivity was 0.56, the specificity was 1.00, and the area under curve was 0.78 (95% confidence interval as 0.63?0.92, P<0.05). (4) Management of colonoscopy-associated colorectal perforation. Of the 18 cases with colonoscopy-associated colorectal perforation, 15 cases underwent laparoscopic perforation repair surgery immediately, 2 cases under-went endoscopic suture, and 1 case received conservative treatment. All the patients with perfora-tion were cured and discharged from hospital, without death due to colonoscopy-associated colorectal perforation. Conclusions:Colonoscopy-associated colorectal perforation is easy to occur at sigmoid colon or rectosigmoid junction. Colorectal diverticulum and abdominal surgery history are indepen-dent risk factors for colonoscopy-associated colorectal perforation. Therapeutic enteroscopy is an independent protective factor for colonoscopy-associated colorectal perforation. Laparoscopic repair of colon perforation has good effects for patients with colorectal perforation.
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Objective:To investigate the influence of nonylphenol (NP) on cytoactive and the expression of G protein-coupled estrogen receptor 30 (GPR30) in human colon cancer SW480 cells.Methods:The experimental study was conducted. The human colon cancer SW480 cells were cultured in vitro. The influence of NP on proliferation, cell cycle, apoptosis and the expression of GPR30 in human colon cancer SW480 cells were analyzed by cell proliferation, cell cycle detection, cell apoptosis and gene expression and protein expression experiments. Cell grouping: SW480 cells cultured with medium were set as the control group, cultured with medium+1×10 ?8 mol/L estradiol were set as the estradiol group, cultured with medium+1×10 ?8 mol/L NP were set as the NP group, cultured with medium+1×10 ?8 mol/L NP+1×10 ?7 mol/L GPR30 specific antagonist G15 were set as the NP+G15 group, respectively. Observation indicators: (1) proliferation index of human colon cancer SW480 cells in the 4 groups; (2) cycle proportion of human colon cancer SW480 cells in the 4 groups; (3) apoptosis index of human colon cancer SW480 cells in the 4 groups; (4) GPR30 messenger RNA(mRNA) expression of human colon cancer SW480 cells in the 4 groups; (5) GPR30 protein expression of human colon cancer SW480 cells in the 4 groups. Measurement data with normal distribution were represented as Mean± SD and one way ANOVA was used for comparison between groups. The least significant difference method was used to test the pairwise comparison. Results:(1) Proliferation index of human colon cancer SW480 cells in the 4 groups. Results of the cell proliferation experiments showed that the proliferation indexes of human colon cancer SW480 cells in the control group, the estradiol group, the NP group and the NP+G15 group were 100.00±0.00, 89.19±4.86, 148.96±6.04 and 120.40±3.39, respectively, showing a significant difference among the 4 groups ( F=21.45, P<0.05). There was a significant difference between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the estradiol group, between the control group and the NP+G15 group ( P>0.05). (2) Cycle proportion of human colon cancer SW480 cells in the 4 groups. Results of the cell cycle detection experiments showed that the proportions of human colon cancer SW480 cells in the S phase of the cell cycles in the control group, the estradiol group, the NP group and the NP+G15 group were 39.96%±2.02%, 36.67%±0.62%, 43.85%±1.02% and 38.29%±1.42%, respectively, showing a significant difference among the 4 groups ( F=10.08, P<0.05). There were significant differences between the control group and the estradiol group, between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the NP+G15 group ( P>0.05). (3) Apoptosis index of human colon cancer SW480 cells in the 4 groups. Results of the cell apoptosis experiments showed that the apoptosis indexes of human colon cancer SW480 cells in the control group, the estradiol group, the NP group and the NP+G15 group were 1.67±0.18, 4.80±0.31, 0.75±0.11 and 2.20±0.19, respectively, showing a significant difference among the 4 groups ( F=136.79, P<0.05). There were significant differences between the control group and the estradiol group, between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the NP+G15 group ( P>0.05). (4) GPR30 mRNA expression of human colon cancer SW480 cells in the 4 groups. Results of quantitative real-time polymerase chain reaction detection showed that the relative expression rates of GPR30 mRNA in human colon cancer SW480 cells of the control group, the estradiol group, the NP group and the NP+G15 group were 1.00±0.00, 0.86±0.05, 1.89±0.27 and 0.64±0.12, respectively, showing a significant difference among the 4 groups ( F=26.61, P<0.05). There were significant differences between the control group and the NP group, between the control group and the NP+G15 group ( P<0.05), and there was no significant difference between the control group and the estradiol group ( P>0.05). (5) GPR30 protein expression human colon cancer SW480 cells in the 4 groups. Results of Western blot detection showed that the relative expression rates of GPR30 protein in human colon cancer SW480 cells of the control group, the estradiol group, the NP group and the NP+G15 group were 1.83±0.16, 1.68±0.15, 3.10±0.30 and 1.26±0.11, respectively, showing a significant difference among the 4 groups ( F=34.05, P<0.05). There were significant differences between the control group and the NP group, between the control group and the NP+G15 group ( P<0.05), and there was no significant difference between the control group and the estradiol group ( P>0.05). Conclusion:Low dose of NP can increase the proliferation index and the proportion of cells in the S phase of the cell cycles, decrease the apoptosis index, and promote the mRNA and protein expression of GPR30 in human colon cancer SW480 cells.
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Objective:To investigate the short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-programmed death-1 (PD-1) antibody therapy for locally advanced rectal cancer.Methods:The prospective study was conducted. The clinicopathological data of 30 locally advanced rectal cancer patients who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from November 2019 to September 2020 were selected. Patients underwent laparos-copic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Observation indicators: (1) situations of the enrolled patients; (2) situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events; (3) preoperative evaluation and surgical situations; (4) postoperative situations and pathological examinations; (5) postoperative adjuvant chemo-therapy and follow-up. Follow-up was conducted using outpatient examination and telephone interview up to March 2022. Patients were followed up once every 3 weeks during the period of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy to detect the adverse events and patients were followed up once every 3 months during the first postoperative 2 years and once every 6 months thereafter to detect tumor recurrence and survival of patients. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:(1) Situations of the enrolled patients. A total of 30 patients were selected for eligibility. There were 17 males and 13 females, aged (57±16)years. Cases with preoperative primary tumor in stage cT3 and cT4 were 22 and 8, respectively. Cases with preoperative clinical lymph node metastasis in stage cN0, cN1, cN2 were 4, 16, 10, respectively. Cases in preoperative clinical stage Ⅱ and Ⅲ were 4 and 26, respectively. Of the 30 patients, there were 21 cases with positive circumferential margin and 12 cases with vascular invasion in extramural of rectum in the preoperative imaging evaluation. Distance from the distal margin of tumor to anal margin and tumor diameter of the 30 patients were 4.7(range, 1.9?9.0)cm and 5.4(range, 2.1?10.0)cm, respectively. There were 28 cases with mismatch repair proficient and 1 case with mismatch repair deficiency in tumor tissues. There was 1 case missing the data of mismatch repair in tumor tissues as failed in biopsy of pathological examination before the treatment. (2) Situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events. All the 30 patients completed preoperative short-course radiotherapy successfully. Of the 30 patients, there were 3 cases not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy and there were 24 cases undergoing 2 courses of the sequential chemotherapy combined with anti-PD-1 antibody therapy and 3 cases undergoing 1 course of the sequential chemotherapy combined with anti-PD-1 antibody therapy. The time interval between ending of radiotherapy and starting of chemotherapy combined with anti-PD-1 antibody therapy of the 27 patients was 12(range, 4?18) days. Cases with leukopenia, cases with endothelial hyperplasia of skin capillaries, cases with radiation proctitis, cases with anemia, cases with peripheral neurotoxicity, cases with neutropenia, cases with thrombocytopenia, cases with fatigue, cases with anorexia, cases with abnormal liver function, cases with hypothyroidism were 24, 22, 21,20, 18, 16, 16, 13, 10, 9, 2 in the 30 patients during the preoperative short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Cases with the above adverse events were improved after symptomatic treatment. (3) Preoperative evaluation and surgical situations. Seven of the 30 patients were in clinical complete remission after preoperative multidisciplinary evaluation and the other 23 patients were not in clinical complete remission. Twenty-seven of the 30 patients underwent laparoscopic radical resection of rectal cancer and 3 patients not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy did not undergo surgery. The time interval between ending of chemotherapy combined with anti-PD-1 antibody therapy and the surgery of the 27 patients were 14(range, 5?141)days. Of the 27 cases, there were 13 cases and 14 cases with 0 and 1 of the preoperative Eastern Cooperative Oncology Group score, respectively, and there were 24 cases undergoing low anterior proctectomy and 3 cases undergoing abdominoperineal excision. The operation time and volume of intra-operative blood loss of the 27 cases were (182±36)minutes and 30(range, 10?150)mL, respectively. Of the 27 cases, there were 16 cases with protective ileostomy and 24 cases with anal preservation. (4) Postoperative situations and pathological examinations. The time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay of the 27 patients undergoing surgery were 2(range, 1?4)days, 3(range, 2?5)days and 8(range, 7?16)days, respectively. Five of the 27 patients had postoperative grade Ⅰ?Ⅱ complications, including 2 cases with incision infection, 1 case with abdominal infection, 1 case with incision hemorrhage and 1 case with venous thrombosis in left lower limb intermuscular. Cases with postoperative complica-tions were improved after symptomatic treatment. Results of postoperative pathological examina-tion showed that the rate of pathologic complete response in 27 patients was 48.1%(13/27). Of the 27 cases, cases in grade 0, grade 1, grade 2, grade 3 of the tumor regression grading were 13, 5, 7, 2, respectively, cases in stage T0, stage Tis, stage T2, stage T3 of the tumor T staging were 13, 1, 5, 8, respectively, cases in stage N0, stage N1, stage N2 of the tumor N staging were 19, 6, 2, respectively, cases in stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ of the tumor TNM staging were 14, 0, 5, 8, respectively. The number of lymph node dissected of the 27 patients was 15(range, 3?29). Of the 27 patients, there was 1 case with positive circumferential margin and 26 cases achieving R 0 resection. None of the 27 patients underwent secondary operation or perioperative death. (5) Postoperative adjuvant chemotherapy and follow-up. Of the 27 patients undergoing surgery, 21 cases underwent post-operative adjuvant chemotherapy, with the cycles of 4(range, 1?6). All the 27 patients were followed up for 20(range, 20?29)months. During the follow-up, 3 cases not achieving pathological complete response had tumor recurrence and no patient died. The disease free survival rate of the 27 patients was 88.9%. Conclusion:Laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with immunotherapy for locally advanced rectal cancer is safe and feasible, with satisfied short-term efficacy.
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Objective:To evaluate the efficacy and safety of modified Atkins diet (MAD) in treating global growth retardation (GDD).Methods:A prospective multicenter clinical controlled study was conducted.The children were included from 8 departments of children′s rehabilitation in Henan Province from July 2017 to October 2017.A total of 154 children who met the inclusion criteria were randomly assigned into the routine treatment group (88 cases) and MAD therapy group (66 cases). A total of 62 children in MAD therapy group and 59 children in routine treatment group completed the study for 15 months.The routine treatment group was provided comprehensive rehabilitation training, and the MAD therapy group was given MAD treatment on the basis of rehabilitation training.Two-way repeated-measures ANOVA was used to compare the differences among datas at different time points. Results:After 3 months, there were significant differences in the scores of the Chinese Version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Children′s Behavior Scale (CBCL) between the 2 groups (all P<0.05). Significant improvement was seen in the MAD group.After 6 months, the MAD therapy group had significantly higher scores on the Gesell Developmental Scale for language and social behavior than the routine treatment group (all P<0.05). After 9 months, the scores of the children in the MAD therapy group were better than those in the routine treatment group in the Gesell Developmental Scale adaptive energy area and the infant-junior high school student social life scale (S-M scale), and the differences were statistically significant (all P<0.05). After 15 months, the fine motor in the MAD therapy group was better than that in the routine treatment group ( P<0.05). At the early stage of MAD therapy, 28 patients showed mild adverse reactions that were reversed after symptomatic treatment.No severe adverse reactions were observed. Conclusions:MAD therapy can improve the neuro-development, emotional and social behaviors, and adaptive behaviors with no severe adverse effects.
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Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.
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Adult , Heart-Assist Devices , Humans , Immunomodulation , Male , Middle Aged , Myocarditis/therapy , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Objective:To explore the value of prognostic model based on ferroptosis-related long non-coding RNA (lncRNA) in predicting the prognosis of patients with colon cancer.Methods:Ferroptosis-related genes were downloaded from FerrDb database, and the RNA sequencing gene data and clinical data of colon cancer patients from the establishment of the database to November 2021 were downloaded from the Cancer Genome Atlas (TCGA) database. Through R3.6.3 software, the colon cancer gene expression data obtained from TCGA database and ferroptosis-related genes obtained from FerreDb database were analyzed to obtain differentially expressed ferroptosis-related genes in colon cancer and normal tissues. The expression correlation between ferroptosis-related genes and lncRNA in colon cancer was calculated by using R3.6.3 software to determine ferroptosis-related lncRNA in colon cancer. The survival-related differentially expressed ferroptosis-related lncRNA was screened and included in the multivariate Cox proportional hazards model to construct a colon cancer prognosis model; and the risk score of colon cancer patients was calculated by the prognostic model according to the lncRNA expression. According to the median risk score, the clinical cases collected from TCGA database were divided into high-risk group and low-risk group with 223 cases in each group. Kaplan-Meier survival analysis was performed for the two groups. The receiver operating characteristic (ROC) curve was used to analyze the effect of prognostic model risk score and clinical characteristics on predicting the survival of all patients. GSEA 4.1.0 software was used for gene set enrichment analysis (GSEA) of lncRNA in high-risk and low-risk groups, and ggpubr package of R3.6.3 software was used for single sample GSEA (ssGSEA) of immune cells and immune function of differentially expressed lncRNA between high-risk and low-risk groups.Results:According to the intersection of ferroptosis-related genes and differentially expressed genes obtained from databases, 65 differentially expressed ferroptosis-related genes were obtained, and 24 lncRNA related to the prognosis of colon cancer were analyzed, and then prognostic model was constructed based on lncRNA. Kaplan-Meier survival analysis showed that the survival of low-risk group was better than that of high-risk group ( P < 0.001); ROC curve analysis showed that the area under the curve (AUC) of 1-, 2-, 3-year survival predicted by the prognostic model risk score was more than 0.75, and the AUC of 1-year survival predicted by the risk score for all patients was greater than age, gender, the National Comprehensive Cancer Network (NCCN), T staging, N staging and M staging. GSEA showed that differentially expressed lncRNA in high-risk and low-risk groups concentrated in tumor and immune-related pathways; ssGSEA showed that there were differences in T cells, macrophages, mast cells, neutrophils, immune stimulation, human leukocyte antigen, type Ⅰ and type Ⅱ interferon response between high-risk group and low-risk group (all P < 0.05), and the expression levels of CD200 and TNFRSF14 at the immune checkpoint were significantly different (both P < 0.01). Conclusions:Ferroptosis-related lncRNA may play an important role in tumor immunity of colon cancer, and it can be used for the prognosis analysis of patients with colon cancer.
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Objective:To observe the effects of cervical region Ⅱ and oral target area optimization on therapeutic efficacy, salivary gland function and oral mucosal response during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer.Methods:A total of 50 patients with oropharyngeal squamous cell carcinoma in Xuzhou Cancer Hospital from January 2012 to May 2017 were collected. According to the random number table, they were divided into normal radiotherapy group (the control group), oral and cervical target area optimization group (the observation group), 25 cases in each group. Both groups were treated with IMRT and platinum-chemotherapy. The control group received bilateral cervical region Ⅱ-Ⅳ lymphatic drainage area irradiation (the positive side of the cervical lymph node included Ⅰ B region), and bilateral cervical region Ⅱ was given a tumor dose of 60 Gy (positive lymph nodes were given intensified irradiation); the observation group was optimized for the target area, and the contralateral cervical region Ⅱ B (the side with no positive lymph node) was given a tumor dose of 50 Gy; the observation group's oral structure was delineated as an organ at risk and the average radiation dose (D mean) was limited to <32 Gy. The differences in radiation dose of parotid gland, acute oral mucosal reaction and long-term xerostomia (6 months after the end of radiotherapy), objective remission rate (ORR), local recurrence rate (LRR), 3-year overall survival (OS) were compared between the two groups. Results:In the control group, the contralateral parotid gland D mean was (29±4) Gy, the proportion of irradiation volume exposed to 34 Gy (V 34) was (48±5)%; in the observation group, contralateral parotid gland D mean was (23±3) Gy, V 34 was (41±5)%, and there are statistically significant differences between the two groups ( t values were 6.14, 4.98, all P < 0.05). In the control group, oral D mean was (35±6) Gy, the proportion of volume exposed to 30 Gy (V 30) was (36±5)%; in the observation group oral D mean was (29±4) Gy, V 30 was (28±4)%, and there were statistically significant differences between the two groups ( t values were 4.11, 5.98, all P < 0.05). The incidence of ≥ grade Ⅱ acute oral mucosal adverse reaction and the duration time of oral mucosal ≥ 2 weeks was 64% (16/25) and 76% (19/25), respectively in the control group, 36% (9/25) and 40% (10/25), respectively in the observation group; and the differences were statistically significant ( χ2 values were 3.92, 6.65; P values were 0.048, 0.009). The incidence of ≥ grade Ⅱ long-term xerostomia reaction was 72% (18/25) and 44% (11/25), respectively in the control group and the observation group, and the difference between the two groups was statistically significant ( χ2 = 4.02, P = 0.044). The ORR, LRR, and 3-year OS rates were 80%, 28%, 48% in the control group, and 76%, 24%, 44% in the observation group. There was no statistically significant difference in the OS between the two groups ( χ2 = 0.04, P = 0.849). Conclusions:Optimization of the target area of the oral and cervical region Ⅱ during IMRT for oropharyngeal carcinoma can improve the function of salivary glands, thereby reducing dry mouth and oral mucosal reactions, improving the quality of life of patients; and it does not affect the efficacy of tumor treatment.
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Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.
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Objective:To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.
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OBJECTIVE@#To investigate the early efficacy of arthroscopic autologous osteochondral grafting in the treatment of recurrent anterior shoulder dislocation.@*METHODS@#From January 2019 to January 2021, 17 patients with recurrent anterior dislocation of shoulder who underwent arthroscopic autologous osteochondral grafting were selected, including 12 males and 5 females, ranging in age from 17 to 55 years old, with a mean of (32.88±12.33) years old. Rowes rating system for Bankart repair(Rowe), Oxford Shoulder Instability Score (OSIS) and Simple Shoulder Test (SST) were compared before operation, 6 months after operation and at the latest follow-up. OSIS and SST used to evaluate shoulder function were recorded before surgery and at the latest follow-up. The shoulder mobility and intraoperative and postoperative complications were also recorded.@*RESULTS@#All 17 patients were followed up, and the duration ranged from 7 to 25 months, with a mean of (18.4±5.4) months. During the follow-up period, there was no re-dislocation, no vascular or nerve injury. Rowe score increased from 26.2±6.0 before operation to 74.4±4.0 and 82.4±3.1 after 6 months and the latest follow-up. There was significant difference in Rowe score between different time points after operation and before operation (P<0.05). The OSIS increased from 37.0±3.6 before operation to 47.4±2.6 and 52.7±2.6 after 6 months and the latest follow-up. There was significant difference in OSIS between different time points after operation and before operation (P<0.05). The SST score increased from 6.8±0.7 before operation to 9.8±0.8, 11.6±2.6 after 6 months and the latest follow-up. There was significant difference in SST score between different time points after operation and before operation (P<0.05). At the latest follow-up, the lateral external rotation and abduction external rotation activities of the patient were significantly improved compared with those before operation.@*CONCLUSION@#This study provides preliminary evidence that arthroscopic autologous osteochondral grafting can achieve satisfactory early clinical outcomes and stability in patients with recurrent anterior shoulder dislocation with glenoid fracture and defect less than <20%, which is a reliable and effective procedure.
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Adolescent , Adult , Arthroscopy/methods , Female , Humans , Joint Instability/surgery , Male , Middle Aged , Range of Motion, Articular , Shoulder Dislocation/surgery , Shoulder Joint/surgery , Young AdultABSTRACT
Objective:To explore the characteristics of pyroptosis-related genes in colon cancer cells screened by bioinformatics, and to verify the constructed prognostic model of colon cancer based on differentially expressed pyroptosis-related genes.Methods:Genetic data of RNA sequencing and clinical data of colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Fifty-two genes associated with pyroptosis were identified by searching the literature and compared with the RNA sequencing gene dataset of colon cancer and normal colon tissues obtained from TCGA database to obtain differentially expressed pyroptosis-related genes in clinical samples. The protein interaction network of differentially expressed pyroptosis-related genes was analyzed by using STRING website and R software. Based on the differential expression of pyroptosis-related genes in clinical samples of TCGA database, colon cancer patients in TCGA database were divided into pyroptosis and non-pyroptosis groups, and genes with significant differential expression between the two groups were screened at P < 0.05 according to gene expression; based on these differentially expressed genes, LASSO Cox regression was used to construct a prognostic model of colon cancer associated with pyroptosis. Patients collected from TCGA database were divided into high risk (≥ median value) and low risk (< median value) groups according to the median value of risk scores calculated by the model, and the overall survival of the two groups was analyzed by Kaplan-Meier survival function. The time ROC package of R software was used to analyze the efficacy of applying risk scores to predict the different survival time of colon cancer patients in TCGA database. Multivariate Cox regression was used to analyze the effects of clinicopathological factors and risk scores calculated by the model on the survival of patients in TCGA database. R software was used to analyze and obtain the differential genes between high and low risk groups of colon cancer patients in TCGA database. R software was used to conduct Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and single sample gene set enrichment analysis of immune cells and immune function (ssGESA) for differentially expressed pyroptosis-related genes. Results:Thirty-eight differentially expressed pyroptosis-related genes between colon cancer tissues and normal tissues of clinical samples were obtained based on data of TCGA database. A prognostic model consisting of 13 pyroptosis-related genes was established by applying LASSO Cox regression, the risk score = 0.118×MID2+0.354×IL20RB+0.083×HOXC11+0.011×TMEM88+0.021×SYNGR3+0.246×UPK3B+0.030×EGFL7+0.109×TMPRSS11E+0.138×IFITM10+0.161×RNF207+0.097×LINGO1+0.202×HEYL+0.025×ROBO3. Survival analysis showed that TCGA database had worse overall survival in the high-risk group than in the low-risk group ( P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve of the prognostic model risk score in predicting the survival of colon cancer patients in TCGA database at 1, 3 and 5 years was all > 0.7. Multivariate Cox regression analysis showed that risk score was an independent influencing factor for survival of colon cancer patients in TCGA database (high risk vs. low risk HR = 3.988, 95% CI 2.865-5.551, P < 0.001). GO and KEGG enrichment analysis showed that the differentially expressed genes between high and low risk groups (SULF1, FBLN2, COL1A1, DES, SFRP2, FNDC1, MYH11, APOE, C3, SPP1, COL1A2, COL10A1, THBS2, AEBP1, CNN1, IGHG1, and SFRP4) were upregulated in the high risk group, which were mainly associated with cellular matrix structural components and extracellular matrix (ECM) receptor interactions. ssGSEA analysis showed that the level of immune cell infiltration was higher in high risk group, especially B cells, macrophages, mast cells, helper T cells, and tumor-infiltrating lymphocytes were higher than those in low risk group; for immune function, chemokine receptors, immune checkpoints, human leukocyte antigens, parainflammation, T cell suppression, T-cell stimulation, and type Ⅱ interferon response in high risk group were higher than those in low risk group. Conclusions:The constructed prognostic model of colon cancer based on pyroptosis-related genes is valuable for predicting the prognosis of colon cancer patients. Pyroptosis-related genes may play an important role in tumor immunity of colon cancer and can be used for prognostic analysis of colon cancer patients.
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Objective:To explore the effect of pretreatment body mass index (BMI) on the prognosis of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy.Methods:The clinical data of 711 patients with locally advanced NSCLC treated with radiotherapy, sequential chemoradiotherapy or concurrent chemoradiotherapy from January 2013 to December 2017 in Cancer Hospital of Chinese Academy of Medical Science and Peking Union Medical College were retrospectively analyzed. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), and the chemotherapy regimens were paclitaxel+carboplatin, pemetrexed+cisplatin or etoposide+cisplatin. The effects of pretreatment BMI and other clinical factors on overall survival (OS) of patients were analyzed. Survival analysis was performed by using Kaplan-Meier method; univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:According to the World Health Organization (WHO) recommended BMI grouping method for Asian, the median OS time of low BMI group (<18.5 kg/m 2, 23 cases), normal BMI group (18.5-23.9 kg/m 2, 293 cases) and high BMI group (≥24.0 kg/m 2, 395 cases) was 17 months (95% CI 11-29 months), 29 months (95% CI 22-36 months) and 30 months (95% CI 27-34 months), respectively. OS in the low BMI group was poorer than that in the normal BMI group and high BMI group ( χ2 = 11.20, P = 0.004). Maximally selected rank statistics was used to determine the optimal cut-off value of BMI for prediction of survival as 21.31 kg/m 2, according to which patients were divided into low BMI group (BMI<21.31 kg/m 2, 130 cases) and high BMI group (BMI≥21.31 kg/m 2, 581 cases), the median OS time of the two groups was 20 months (95% CI 17-27 months) and 32 months (95% CI 28-35 months), respectively. OS in the low BMI group was poorer than that in the high BMI group ( χ2 = 12.30, P < 0.001). Multivariate analysis showed that age ≥ 65 years old, male, Karnofsky score < 80 points, low BMI, smoking, histological type of squamous cell carcinoma and radiotherapy alone were independent risk factors for OS (all P < 0.05). Conclusions:For patients with unresectable locally advanced NSCLC who received chemoradiotherapy, those with low pretreatment BMI have poor prognosis.
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Digital and intelligent technology is an important driving force to promote the transformation and innovation of medical service mode and improve service quality. In February 2020, Peking Union Medical College Hospital established an intelligent outpatient pre-admission medical history collection system in order to improve the intelligent level of clinical application business system and the medical experience of outpatients.The system consisted of artificial intelligence capability layer, application service layer, capability resource layer and user application layer and hardware technology architecture. By docking with the hospital information system and using mobile terminal App, patients could submit pre-admission medical history information by themselves, and generate structured patient history for the visiting doctors to call. By November 2021, the pre-admission medical history collection system had covered 80% of the departments of the hospital, serving 1.68 million people in total, and the patient filling rate had reached 60%. The duration of patient′s medical history collection and the duration of doctor′s outpatient electronic medical record writing had been continuously shortened, greatly improving the efficiency of outpatient medical services.
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Objective:Pretibial myxedema (PTM) is a localized myxedema characterized by excessive dermal hya-luronan (HA) deposition and elevated serum TSH receptor antibody (TRAb). In this study, we investigated the effects of TRAb and its subtypes, stimulating antibody [TSAb (M22)] and inhibitory antibody[TBAb (K1-70)], on the synthesis of hyaluronic acid produced by PTM primary dermal fibroblasts.Methods:Normal and PTM dermal fibroblasts were isolated and stimulated with M22, K1-70, and IgG from patients respectively. HA concentration in the supernatant before and after stimulation was tested by ELISA. The protein level and phosphorylation variation of CEMIP, HAS2 and PI3K-AKT pathway were detected by Western blot.Results:IgG from patients (TRAb 8.4 IU/L) significantly stimulated the extracellular accumulation of HA in PTM primary fibroblasts. Similarly, both M22 and K1-70 also upregulated HA level in the supernatant, though K1-70 seemed much more effecitve. After treatment with IgG, M22, and K1-70, the expression of HAS2 increased and the expression of CEMIP decreased; meanwhile, p-PI3K and p-AkT increased. Among them, further study on K1-70, promoting HA production by regulating PI3K-AkT signal pathway could be inhibited by PI3K inhibitor (LY294002).Conclusion:TSAb (M22) and TBAb (K1-70), especially TBAb, increase HAS2 and inhibit CEMIP expression by activating PI3-AKT signaling pathway in PTM fibroblasts, leading to increased extracellular HA level.
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The ectopic salivary gland refers to the presence of salivary gland tissue in an area other than the site where salivary glands normally exist. They often occur near the line connecting the external ear canal and the medial border of the clavicle. It is extremely rare to occur in the urogenital system. This paper retrospectively analyzed the clinicopathological data of a patient with ectopic salivary glands accidentally discovered due to testicular torsion. Patients are generally asymptomatic. If there is no fistula leading to the skin or mucosal surface, it is difficult to find clinically. The diagnosis depends on postoperative pathological examination. For ectopic salivary glands, surgery is required regardless of the location.
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Circulating tumor DNA (ctDNA) has been the most common biomarker in liquid biopsy because of non-invasive detection and overcoming intratumor heterogeneity. Lung cancer remains the leading cause of cancer-related morbidity and mortality all over the world, with non-small cell lung cancer (NSCLC) constituting 85% of the total cases. Radiotherapy plays an important role in phase Ⅰ-Ⅳ NSCLC. It can not only kill tumor cells to eradicate cancer directly, but also increase the release of ctDNA indirectly, which improves the accuracy of liquid biopsy. As a result, ctDNA has the potential to be widely used in radiotherapy for NSCLC. In this review, research progress on ctDNA in the diagnosis, prognosis assessment, recurrence detection and response prediction in NSCLC patients treated with radiotherapy were summarized.
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Objective:To investigate the feasibility of surface-guided hypo-fractionated radiotherapy for intracranial metastasis with open face mask immobilization.Methods:Nineteen patients treated with hypo- fractionated radiotherapy for intracranial metastasis in our hospital were included. Before the start of treatment, each patient underwent simulation with open face mask immobilization. During the treatment, cone-beam CT(CBCT)images were collected for verification each time. Laser-guided positioning was used for the first time in the treatment, and surface images were captured after six-dimensional position correction as the reference images for subsequent treatment. Subsequent treatment was randomly divided into laser-guided positioning group(LG, 85/F)and optical surface-guided positioning group(SG, 101/F). The six-dimensional error data of patients with two positioning methods were compared and expressed as mean ± standard deviation. Meanwhile, the correlation and consistency between the optical surface error data and the gold standard CBCT error data were compared in the laser-guided fraction. GraphPad Prism 6.0 software was used for data processing and mapping, and SPSS 21.software was used for mean analysis and normality test. Pearson correlation analysis was used to analyze the correlation, and Bland-Altman plot analysis was used to test the coincidence between two methods.Results:Compared with the laser-guided positioning, the 3D error of optical surface-guided positioning was reduced from(0.35±0.16)cm to(0.14±0.07)cm. The Pearson coefficient of correlation along all three directions was less than 0.01,R 2 was 0.91,0.70 and 0.78 on Lat, Lng and Vrt, and R 2 was 0.75,0.85 and 0.77 on Pitch, Roll and Rtn(all P<0.01), respectively. The measurement results of two methods were positively correlated. The Bland-Altman plot analysis showed that the 95% limits of agreement were within preset 3 mm tolerance([-0.29 cm, 0.19 cm], [-0.25 cm, 0.25 cm], [-0.27 cm, 0.19 cm]), and the 95% limits of agreement were within preset 3° tolerance(Pitch[-1.76°,1.76°], Roll[-1.54°,1.60°], ROT[-2.18°,1.69°]), indicating agreement between two methods. Conclusions:The optical surface-guided positioning can reduce the setup errors in the hypo-fractionated radiotherapy for intracranial metastasis with open face mask immobilization. The optical surface error and CBCT error have good correlation and agreement.
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Objective:To evaluate the effects of the alpha-lipoic acid on hepatic ischemia/reperfusion (I/R) injury and the role of (ALDH2).Methods:This experiment was performed in two parts in vivo and in vitro experiments. In vivo experiment Twenty-four male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (Sham group), hepatic I/R group (IR group), and hepatic I/R plus α-lipoic acid group (IR+ ALA group) and hepatic I/R+ α-lipoic acid+ daidzin group (IR+ ALA+ D group). Hepatic I/R was induced by occlusion of the left and middle hepatic lobes for 60 min, followed by 6 h of reperfusion in anesthetized rats.In IR+ ALA+ D group, ALDH2 inhibitor daidzin 50 mg/kg was intraperitoneally injected at 45 min before ischemia.Alpha-lipoic acid 100 mg/kg was intraperitoneally injected at 30 min before ischemia in IR+ ALA group and IR+ ALA+ D group.Blood samples from the inferior vena cava were collected at the end of reperfusion to determine serum AST and ALT activities.Then the rats were sacrificed, and livers were removed for microscopic examination of pathological changes of the lung tissues which were scored and for determination of ALDH2 activity, level of reactive oxygen species (ROS) and expression of 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) (by immuno-histochemistry). In vitro experiment Rat BRL-3A hepatocytes cultured in vitro were divided into 4 groups ( n=15 each) by the random number table method: control group (C group), hypoxia-reoxygenation group (HR group), hypoxia-reoxygenation+ α-lipoic acid group (HR+ ALA group) and hypoxia-reoxygenation+ α-lipoic acid+ daidzin group (HR+ ALA+ D group). BRL-3A hepatocytes were exposed to 95% N 2-5% CO 2 in an incubator at 37 ℃ for 6 h followed by reoxygenation with 95% O 2-5% CO 2 for 24 h. At 60 min before hypoxia, alpha-lipoic acid 100 μmol/L was addded in HR+ ALA group, and alpha-lipoic acid 100 μmol/L and daidzin 60 μmol/L were added in HR+ ALA+ D group.At 24 h of reoxygenation, cell viability was measured by CCK-8 method, ALDH2 activity was determined by spectrophotometry, ROS level was detected by DCFH-DA fluorescent probe method, and mitochondrial membrane potential (MMP) was measured by JC-1 method. Results:In vivo experiment Compared with Sham group, the serum AST and ALT activities, liver injury score, level of ROS in liver tissues and expression of 4-HNE and MDA were significantly increased ( P<0.05), and no significant change was found in ALDH2 activity in IR group ( P>0.05). Compared with IR group, the serum AST and ALT activities, liver injury score, level of ROS in liver tissues and expression of 4-HNE and MDA were significantly decreased, and the ALDH2 activity was increased in IR+ ALA group ( P<0.05). Compared with IR+ ALA group, the serum AST and ALT activities, liver injury score, level of ROS in liver tissues and expression of 4-HNE and MDA were significantly increased, and the ALDH2 activity was decreased in HR+ ALA+ D group ( P<0.05). In vitro experiment Compared with C group, the cell viability and MMP were significantly decreased, and the level of ROS was increased ( P<0.05), and no significant change was found in the activity of ALDH2 in HR group ( P>0.05). Compared with HR group, the cell viability, ALDH2 activity and MMP were significantly increased, and the level of ROS was decreased in HR+ ALA group ( P<0.05). Compared with HR+ ALA group, the cell viability, ALDH2 activity and MMP were significantly decreased, and the level of ROS was increased in HR+ ALA+ D group ( P<0.05). Conclusions:Alpha-lipoic acid can reduce hepatic I/R injury in rats, and the mechanism is related to activation of ALDH2, reduction of accumulation of toxic aldehyde and restoration of MMP.