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Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t 1/2 > 14 days) compared to t 1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.
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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The injured organ is the main target of treatment. Organic functional reserve refers to the ability of an organ or system to return to its original physiological state following acute physiological stress or pathological injury, which has not received widespread attention. The organ reserve capacity is expected to complement the existing sepsis-related scoring system to optimize disease severity grading and evaluate prognosis. Source control, appropriate using of antibiotics and organ supporting can reduce further damage of organ reserve capacity, while nutritional therapy and rehabilitation may enhance it. Therefore, the authors believe that in further basic theoretical research and clinical practice, more attention can be paid to the monitoring and management of organ reserve capacity in sepsis, which may help improving the diagnosis and treatment of sepsis and prognosis of patients.
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Objective:To investigate the risk factors for abdominal infection after liver transplantation (LT).Methods:The retrospective case-control study was conducted. The clinical data of 356 patients who underwent LT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2015 to December 2018 were collected. There were 273 males and 83 females, aged from 21 to 67 years, with the median age of 46 years. Observation indications: (1) abdominal infec-tion after LT and distribution of pathogens; (2) analysis of risk factors for abdominal infection after LT; (3) follow-up and survival. Follow-up was performed using outpatient examination and tele-phone interview to detect postoperative 1-year survival rate and cases of death up to June 2020. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were described as M(range). Count data were expressed as absolute numbers or percentages. Univariate analysis was conducted using the chi-square test, t test, Mann-Whitney U test and Fisher exact probability. Multivariate analysis was done using the Logistic regression model. The Kaplan-Meier method was used to calculate sruvival time and survival rates. Log-Rank test was used for survival analysis. Results:(1) Abdominal infection after LT and distribution of pathogens: 63 of 356 recipients had abdominal infection after LT, with the overall incidence of 17.70%(63/356). Of the 63 recipients, 41 cases had abdominal infection within postoperative 2 weeks, 17 cases had multi-drug resistant organism infection. A total of 116 strains of bacteria were isolated from 63 recipients with abdominal infection, 52 of which were gram-negative bacteria, 48 were gram-positive bacteria, 16 were fungi. (2) Analysis of risk factors for abdominal infection after LT: results of univariate analysis showed that preoperative model for end-stage liver disease (MELD) score, preoperative serum albumin, preoperative leukocytes, preoperative prothrombin time, preoperative alanine aminotransferase, preoperative aspartate aminotransferase, operation time, volume of intraoperative blood loss, days of postoperative antibiotic use, postoperative renal failure, postoperative delayed graft function,duration of postoperative intensive care unit stay were related factors for abdominal infection after LT ( Z=-2.456, t=-1.982, Z=-3.193, -2.802, -2.336, -2.276, -2.116, -3.217, χ2=15.807, 10.395, 6.750, Z=-4.468, P<0.05). Liver retransplantaiton and postoperative bile leakage were related factors for abdominal infection after LT ( P<0.05). Results of multivariate analysis showed that preoperative MELD score>20 and liver retransplantation were independent risk factors for abdominal infection after LT ( odds ratio=2.871, 12.875, 95% confidence interval as 1.106-7.448, 1.290-128.521, P<0.05). (3) Follow-up and survival: 356 recipients were followed up for 1-66 months, with a median follow-up time of 32 months. The postoperative 1-year overall survival rate of 63 recipients with abdominal infection and 293 recipients without abdominal infection were 84.60% and 97.03%, respectively, showing a significant difference ( χ2=11.660, P<0.05). During the follow-up, 58 recipients died. Conclusion:Preoperative MELD score>20 and liver retransplantation are independent risk factors for abdominal infection after LT.
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Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.
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Enteral nutrition is an indispensable part of the treatment for critically ill patients. Various authoritative guidelines point out that early enteral nutrition is the key to improve the prognosis of disease. The key to improve and promote standardized enteral nutrition for criti-cally ill patients is the application of guidelines in the clinical practice. Based on clinical practice and theoretical basis, the authors propose a new insight into enteral nutrition and a new nutritional strategy of "individual treatment, circular evaluation, channel basis, quality-quatity balance, step-up achievement" for critically ill patients on basis of a 5W1H mindset.
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Objective:To investigate the prognostic value of preoperative red blood cell distribution width (RDW) for hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 025 HCC patients who were admitted to three medical centers (586 in the First Affiliated Hospital of Xi'an Jiaotong University, 248 in the Second Affiliated Hospital of Xi'an Jiaotong University and 191 in the Qinghai University Affiliated Hospital) between April 2002 and August 2017 were collected. There were 809 males and 216 females, aged (54±11)years, with a range from 16 to 83 years. The average coefficient of variation of RDW (RDW-CV) of 1 025 patients was 14.3%. Of 1 025 patients, 347 cases had high RDW of RDW-CV >14.3%, and 678 had low RDW of RDW-CV ≤14.3%. Observation indicators: (1) clinico-pathological data of HCC patients; (2) influencing factors for prognosis of HCC patients; (3) follow-up and survival. (4) stratified analysis of independent influencing factors. Follow-up was performed by outpatient examination, telephone interview or internet interview to detect postoperative survival of patients up to October 2017. Measurment data with normal distribution were represented as Mean±SD, and measurment data with skewed distribution were described as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The Graphpad Prism 7.0 was used to draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard model. Results:(1) Clinicopathological data of HCC patients: cases with age ≤70 years or >70 years, cases without cirhhosis or with cirhhosis , cases of Child-Pugh grade A or Child-Pugh grade B or C, cases with the level of alpha fetoprotein (AFP) ≤200 μg/L or >200 μg/L, cases with single tumor or multiple tumors were 313, 34, 152, 186, 161, 53, 158, 143, 186, 109 for high RDW patients, versus 641, 37, 359, 310, 415, 48, 367, 227, 547, 131 for low RDW patients, respectively, showing significant differences in above indicators between the two groups ( χ2=6.709, 6.787, 23.906, 7.114, 34.375, P<0.05). (2) Influencing factors for prognosis of HCC patients: results of univariate analysis showed that age, Child-Pugh grade, AFP, RDW-CV, tumor diameter, the number of tumors were related factors for prognosis of patients ( hazard ratio=1.388, 1.432, 1.534, 1.455, 2.813, 1.505, 95% confidence interval as 1.004-1.920, 1.086-1.887, 1.263-1.864, 1.211-1.748, 2.293-3.450, 1.173-1.932, P<0.05 ). Results of multivariate analysis showed that age, RDW-CV, tumor diameter and the number of tumors were independent factors for prognosis of patients ( hazard ratio=1.020, 1.340, 2.427, 1.438, 95% confidence interval as 1.007-1.032, 1.027-1.749, 1.801-3.272, 1.057-1.956, P<0.05). (3) Follow-up and survival: 1 025 patients were followed up for 1-124 months, with a median follow-up time of 25 months. The median survival time was 23 months for high RDW patients, versus 44 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=11.640, P<0.05). (4) Stratified analysis of independent influencing factors: the results of stratified analysis of 3 independent influencing factors including age, tumor diameter and the number of tumors showed that in the 954 patients with age ≤70 years, the median survival time was 25 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=14.030, P<0.05). In the 71 patients with age >70 years, the median survival time was 11 months for high RDW patients, versus 29 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=0.933, P>0.05). In the 459 patients with tumor diameter ≤5 cm, the median survival time was 44 months for high RDW patients, versus 76 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=8.660, P<0.05). In the 487 patients with tumor diameter >5 cm, the median survival time was 14 months for high RDW patients, versus 18 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=2.950, P>0.05). In the 733 patients with single tumor, the median survival time was 20 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=13.530, P<0.05). In the 240 patients with multiple tumors, the median survival time was 15 months for high RDW patients, versus 20 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=6.820, P<0.05). Conclusions:Preoperative RDW can be used as a predictive index for prognosis of HCC patients, and patients with high RDW have poorer prognosis. RDW have better predictive value in patients with age ≤70 years or tumor diameter ≤5 cm.
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Objective:To construct a prediction model for the prognosis of breast cancer patients with long non-coding RNA expression characteristics.Methods:To construct a long non-coding RNA(LncRNA) model for predicting the prognosis of breast cancer patients.Methods Analyzing LncRNA expression profiles and clinical characteristics of 1 081 breast cancer patients in the cancer genome atlas (TCGA) database.Performing differential expression analysis and univariate analysis on 112 paired breast cancer and normal breast tissues′ transcriptome sequencing data in the TCGA database, and screened for differentially expressed (DELncRNAs) that significantly correlated with the prognosis of BRCA (To reduce batch effects, sequencing data has been normalized using the DESeq function). One thousand eighty-one breast cancer patients were randomly divided into two groups: training set (541) and validation set (540). Performing Cox proportional hazard regression using DELncRNAs and establishing a multi-LncRNA prognosis model in the training set, followed by proportional hazards assumption test(PH assumption test). Patients were divided into high-risk and low-risk groups based on calculated risk score.Kaplan-Meier method was used for survival analysis, and 540 patients′ data were used for validation.To evaluate the prognostic value of the model in patients with squamous cell carcinoma of the lung and hepatocarcinoma in TCGA database.Gene Set Enrichment Analysis (GSEA) was used to analyze the specific mechanism of lncrna affecting the survival of patients.Results:There were 2815 differentially expressed genes screened by transcriptome sequencing, 91 of which were significantly related to the prognosis of breast cancer patients ( P<0.05). Based on the Cox regression analysis of 91 delncrna expression data from 541 breast cancer patients in training set, a Cox proportional risk regression model was constructed based on 5 LncRNA (training set AUC=0.746, validation set AUC=0.650): AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283, and PH assumption test( P=0.388). K-M survival analysis showed that the survival time of high-risk group was significantly worse than that of low-risk group (median survival time: 7.049 and 12.21 years, HR 0.367, 95% CI0.228-0.597, P<0.001), and the survival time of high-risk group was significantly shorter than that of low-risk group (median survival time: 7.57 and 10.85 years, HR 0.412, 95% CI0.214-0.793, P<0.001). Similar prediction results were also obtained in other cancer species of TCGA: lung squamous cell carcinoma ( HR 0.604, 95% CI0.383-0.951, P=0.007) and liver cell carcinoma ( HR 0.551, 95% CI0.307-0.987, P=0.011). GSEA results suggested that the expression patterns of the above five LncRNA were related to the cell cycle regulation of tumor cells. Conclusion:The prognostic model constructed based on expression profile of AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283 can be used to predict the prognosis of breast cancer patients, which is helpful to further guide clinical treatment.
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Source control is the core of intra-abdominal infections (IAIs) treatment, in which precise positioning and effective drainage is the key and aporia. On the basis of membrane anatomy theory and understanding of anatomic structural abnormality under IAIs, the authors propose the concept of 'abdominal partition under IAIs’ in order to locate the source of infection and design of safe drainage path precisely, which could improve the diagnosis and treatment of IAIs and the prognosis.
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Objective:To predict the efficacy and safety of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections using Bayesian network meta analysis.Methods:Databases including PubMed, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database were searched for literatures from January 1990 to May 2018 with the key words of ( "intraabdominal infections" [MeSH Terms]) AND ( "Cephalosporins*" [MeSH Terms]) AND ( "randomized controlled trial" [MeSH Terms]),腹腔感染,继发性腹膜炎,腹腔脓肿,头孢. The randomized controlled trials (RCTs) about comparison of efficacy and safety between cephalosporins antibiotics combined with metronidazole versus other antibiotics for intra-abdominal infections were received and included. Experimental group included patients who received cephalosporins antibiotics combined with metronidazole for intra-abdominal infections, and control group included patients who received other antibiotics for intra-abdominal infections. The primary outcomes were the clinical cure rates, microbial clearance rate and incidence of serious adverse drug reactions. R 3.6.2 software random Bayesian model was used for meta analysis. The Markov Chain Monte Carlo was used for direct evaluation and indirect prediction. The tracing method, density plotting and leverage figure method were used to evaluate the model convergence and stability. No closed loop formed between intervention measures, so there was no need to evaluate consistency.Results:(1) Document retrieval: a total of 18 available RCTs were enrolled. There were 6 792 patients, including 3 402 in the experimental group, 3 390 in the control group. (2) Results of Bayesian network meta analysis. ① The clinical cure rates of the third generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole [ odds ratio ( OR)=0.46, 0.61, 95% confidence interval( CI) as 0.26-0.81, 0.38-0.97, P<0.05]. There was no significant difference in the clinical cure rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=1.03, 95% CI as 0.59-1.80, P>0.05). ② The microbial clearance rates of the fifth generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole ( OR=0.84, 0.41, 95% CI as 0.73-0.98, 0.23-0.74, P<0.05). There was no significant difference in the microbial clearance rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=0.76, 95% CI as 0.27-1.80, P>0.05). ③ The incidence of serious adverse drug reactions was significantly lower for the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins antibiotics+ cetronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, quinolones+ metronidazole, and tigecycline than for quinolones ( OR=0.13, 0.13, 0.14, 0.13, 0.15, 0.13, 95% CI as 0.03-0.50, 0.02-0.98, 0.02-0.75, 0.02-0.59, 0.02-0.78, 0.02-0.57, P<0.05). Compared with carbapenems, the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole had no significant difference in the incidence of serious adverse drug reactions ( OR=0.96, 1.00, 1.10, 95% CI as 0.52-1.60, 0.31-3.50, 0.49-2.30, P>0.05). (3) Ranking of the efficacy and safety. ① The ranking list for clinical cure rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, synthetic penicillins, the second generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 51.73%, 35.72%, 22.57%, 31.37%, 24.98%, 32.82%, 34.69%, 29.05%, 72.36%, respectively. ② The ranking list for microbial clearance rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, the second generation cephalosporins+ metronidazole, synthetic penicillins, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 89.62%, 77.01%, 38.60%, 20.94%, 26.26%, 26.39%, 22.22%, 20.19%, 62.55%, respectively. ③ The ranking list for incidence of serious adverse drug reactions of different therapeutic regimens showed from high to low as quinolones, quinolones+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, the fourth generation cephalosporins+ metronidazole. The corresponding ranking probabilities of above regimens were 96.21%, 30.46%, 21.09%, 25.27%, 27.26%, 19.45%, 31.69%, respectively. Conclusion:In the treatment of middle- and low-risk intra-abdominal infections, it is recommended to empirically use cephalosporins+ metronidazole instead of carbapenems.
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Objective:To investigate the risk factors of portal vein system thrombosis (PVST) after portoazygous devascularization in patients with portal hypertension.Methods:Clinical data of 215 patients with portal hypertension treated by splenectomy at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi′an Jiaotong University from Jan 2012 to Dec 2017 were retrospectively analyzed. Univariate analysis of variance and Logistic regression were used to analyze the clinical risk factors that may lead to PVST.Results:The incidence of PVST was 43.7%(94/215). Univariate analysis of variance showed that the diameter of portal vein, the diameter of splenic vein, the thickness of spleen, laparoscopic or open surgery, and postoperative platelet count were correlated with postoperative PVST (all P<0.05). Logistic regression analysis showed that splenic vein diameter ( OR=3.137, 95% CI 1.391-7.076, P=0.006), splenic thickness ( OR=3.065, 95% CI 1.418-6.626, P=0.004) and postoperative platelet count ( OR=7.446, 95% CI 3.057-18.137, P=0.000) were independent risk factors for PVST in patients with portal hypertension. Conclusion:Postoperative PVST in patients with portal hypertension are more likely to develope when preoperative splenic vein ≥11 mm, splenic thickness ≥60 mm and platelet count ≥300×10 9/L on the 7th day after operation.
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Objective@#To investigate the safety and feasibility of laparoscopic remedial surgery in patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection.@*Methods@#The clinical and follow-up data of 12 patients who didn′t reach the cure criterion of early colorectal cancer and then underwent endoscopic resection was collected. The clinicalpathological features and remedial indications were analyzed to evaluate the effects of laparoscopic remedial surgery.@*Results@#The average number of lymph nodes in the lymph node dissection was 15 during remedial surgery, and 3 of them had lymph node metastasis. Among the 3 patients with residual cancer, two cases were poorly differentiated, 1 case was moderately differentiated, 1 case was positive for basal margin, and 1 case had vascular invasion. No lymph node metastasis occurred in the 9 patients who had no residual cancer. Among these, 8 cases were moderately differentiated, 1 case was poorly differentiated and 2 cases had positive basal margin. The average follow-up duration was 40 months and all 12 patients were in a state of survival at the last follow-up. During the follow-up of the 3 patients with residual cancer, 1 patient received adjuvant chemotherapy with unknown prognosis; 1 patient received postoperative adjuvant radiochemotherapy, and lung metastasis occurred; 1 patient did not receive any treatment after surgery and survived for 33 months.@*Conclusions@#Laparoscopic remedial surgery is a safe and feasible remedy for patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. However, the choice of remedial strategy for colorectal carcinoma needs further investigation for patients with no vascular invasion, high degree of differentiation, and negative basal margin.
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Objective@#To evaluate the efficacy and safety of oXiris hemofilter for septic shock patients.@*Methods@#Clinical data of septic shock patients receiving continuous renal replacement therapy (CRRT) with oXiris hemofilter in department of surgical intensive care unit (SICU) of the First Affiliated Hospital of Xi'an Jiaotong University from March 1st, 2018 to July 20th, 2019 were retrospectively analyzed. The heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO2/FiO2), lactate (Lac), platelet count (PLT), serum procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), noradrenaline (NE) dosage, acute physiology and chronic health evaluationⅡ(APACHEⅡ) and sequential organ failure score (SOFA) were compared before and after oXiris treatment and the prognosis were also analyzed.@*Results@#Six patients with septic shock were included [5 males, the average age was (56.3±11.8) years old]. A total of 13 oXiris hemofilter sets were performed during treatment. Compared with before treatment, the HR, IL-6 and CRP levels were significantly decreased after treatment [HR (bpm): 93.8±9.7 vs. 133.5±18.3, IL-6 (ng/L): 509.2±169.6 vs. 3 739.8±618.2, CRP (mg/L): 169.1±148.3 vs. 277.8±68.7, all P < 0.05], MAP, PaO2/FiO2 and PLT were significantly increased [MAP (mmHg, 1 mmHg = 0.133 kPa): 73.3±2.2 vs. 63.3±1.6, PaO2/FiO2 (mmHg): 166.8±40.4 vs. 95.1±56.2, PLT (×109/L): 73.3±27.5 vs. 41.2±21.4, all P < 0.05]; meanwhile, NE dosage, APACHEⅡ and SOFA scores were significantly decreased [NE (μg·kg-1·min-1): 0.4±0.3 vs. 1.2±0.7, APACHEⅡ: 18.8±6.9 vs. 30.0±7.3, SOFA: 11.7±4.2 vs. 17.3±2.1, all P < 0.05]. Although Lac and PCT decreased after treatment, there was no significant difference [Lac (mmol/L): 3.5±2.1 vs. 6.1±3.2, PCT (μg/L): 37.7±48.3 vs. 85.1±32.8, both P > 0.05]. At the end, 3 of the 6 patients survived and the others were discharged again medical advice. The length of SICU stay was 3 to 23 days, with an average of (13.0±8.5) days. No adverse events occurred during the treatment.@*Conclusion@#oXiris hemofilter can effectively remove inflammatory mediators in circulation, significantly improve hemodynamic status and severity, and may be considered as a safe and reliable treatment modality for septic shock patients.
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Intra-abdominal infections (IAIs) are common in the clinical practice, which include a variety of patholo-gical conditions. Severe IAIs can lead to sepsis, secondary organ dysfunction, and threaten the lives of patients. Patients with IAIs are under a high metabolic reaction, and often have gastrointestinal dysfunction, manifesting as impaired intestinal mucosal barrier function, out of control in intestinal flora regulation, and continuous loss of nutrients. The body is in a malnutrition condition, and body resistance severely declines, which further aggravates disease progression. Intestinal micro-ecology is the largest and most complex ecosystem in the human body. In the case of coexistence of many bacteria, the synergy and antagonism between different strains maintain the balance of digestive tract microecology. Intestinal flora and nutritional status under IAIs have their particularity. Understanding the mechanism of intestinal flora abnormalities under IAIs, reasonable and effective nutritional support treatment and management is essential for improving the prognosis of patients with IAIs.
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Intra-abdominal infections (IAIs) are common in the clinical practice,which include a variety of pathological conditions.Severe IAIs can lead to sepsis,secondary organ dysfunction,and threaten the lives of patients.Patients with IAIs are under a high metabolic reaction,and often have gastrointestinal dysfunction,manifesting as impaired intestinal mucosal barrier function,out of control in intestinal flora regulation,and continuous loss of nutrients.The body is in a malnutrition condition,and body resistance severely declines,which further aggravates disease progression.Intestinal micro-ecology is the largest and most complex ecosystem in the human body.In the case of coexistence of many bacteria,the synergy and antagonism between different strains maintain the balance of digestive tract microecology.Intestinal flora and nutritional status under IAIs have their particularity.Understanding the mechanism of intestinal flora abnormalities under IAIs,reasonable and effective nutritional support treatment and management is essential for improving the prognosis of patients with IAIs.
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Objective To evaluate the efficacy and safety of oXiris hemofilter for septic shock patients. Methods Clinical data of septic shock patients receiving continuous renal replacement therapy (CRRT) with oXiris hemofilter in department of surgical intensive care unit (SICU) of the First Affiliated Hospital of Xi'an Jiaotong University from March 1st, 2018 to July 20th, 2019 were retrospectively analyzed. The heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO2/FiO2), lactate (Lac), platelet count (PLT), serum procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), noradrenaline (NE) dosage, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) and sequential organ failure score (SOFA) were compared before and after oXiris treatment and the prognosis were also analyzed. Results Six patients with septic shock were included [5 males, the average age was (56.3±11.8) years old]. A total of 13 oXiris hemofilter sets were performed during treatment. Compared with before treatment, the HR, IL-6 and CRP levels were significantly decreased after treatment [HR (bpm): 93.8±9.7 vs. 133.5± 18.3, IL-6 (ng/L): 509.2±169.6 vs. 3739.8±618.2, CRP (mg/L): 169.1±148.3 vs. 277.8±68.7, all P < 0.05], MAP, PaO2/FiO2 and PLT were significantly increased [MAP (mmHg, 1 mmHg = 0.133 kPa): 73.3±2.2 vs. 63.3±1.6, PaO2/FiO2 (mmHg): 166.8±40.4 vs. 95.1±56.2, PLT (×109/L): 73.3±27.5 vs. 41.2±21.4, all P < 0.05]; meanwhile, NE dosage, APACHEⅡ and SOFA scores were significantly decreased [NE (μg·kg-1·min-1): 0.4±0.3 vs. 1.2±0.7, APACHEⅡ:18.8±6.9 vs. 30.0±7.3, SOFA: 11.7±4.2 vs. 17.3±2.1, all P < 0.05]. Although Lac and PCT decreased after treatment, there was no significant difference [Lac (mmol/L): 3.5±2.1 vs. 6.1±3.2, PCT (μg/L): 37.7±48.3 vs. 85.1±32.8, both P > 0.05]. At the end, 3 of the 6 patients survived and the others were discharged again medical advice. The length of SICU stay was 3 to 23 days, with an average of (13.0±8.5) days. No adverse events occurred during the treatment. Conclusion oXiris hemofilter can effectively remove inflammatory mediators in circulation, significantly improve hemodynamic status and severity, and may be considered as a safe and reliable treatment modality for septic shock patients.
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Objective To evaluate the clinical efficacy and safety of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP) receiving percutaneous drainage (PCD). Methods Clinical data of SAP patients receiving PCD admitted to department of hepatobiliary surgery of the First Affiliated Hospital of Xi'an Jiaotong University from November 11th 2015 to May 13th 2018 were retrospectively analyzed. The patients were divided into CRRT group and control group according to whether or not receiving CRRT. Demographic data, relevant variables before and after PCD, complication and outcome were all compared. Results A total of 75 patients were included in the study, 30 were treated with application of CRRT and 45 without CRRT. ① There was no significant difference in gender, age, body mass index (BMI), medical history (smoking, drinking), complications (cardiovascular disease, chronic lung disease, diabetes, chronic renal insufficiency), etiology (gallstone, alcohol abuse, hyperlipidemia and others), or white blood cell count (WBC), C-reactive protein (CRP), serum procalcitonin (PCT), fluid resuscitation, mechanical ventilation, vasoactive agent or intra-abdominal pressure within 48 hours after admission between the two groups. However, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score within 48 hours after admission of CRRT group was significantly higher than that of control group (18.3±4.5 vs. 12.8±6.2, P < 0.05). ② There was no significant difference in WBC, PCT, APACHEⅡ score or computed tomography severity index (CTSI) before PCD between the two groups. There was no significant difference in the position or times of PCD procedure between the two groups, but the time interval of PCD in the CRRT group was significantly longer than that in the control group (days: 19.4±5.4 vs. 12.8±2.2, P < 0.05). Meanwhile, there was no significant difference in drainage of fluid properties, incidence of abdominal bleeding, infection, gastrointestinal fistula, endoscopic removal of necrotic tissue, laparotomy for removal of necrotic tissue or the time from PCD to endoscopy or laparotomy between two groups. However, the length of intensive care unit (ICU) stay and the length of hospital stay in the CRRT group were significantly longer than those in the control group (days: 23.2±8.5 vs. 15.3±12.1, 51.2±21.2 vs. 31.2±14.0, both P < 0.01). ③ Kaplan-Meier survival analysis showed that there was no significant differences in 1-year or 3-year cumulative survival rates between the two groups (χ21 = 0.097, P1 = 0.755; χ22 = 0.013, P2 = 0.908). Conclusions CRRT is safe and feasible in the treatment of SAP patients receiving PCD procedure. It does not increase the risk of bleeding and may delay the time interval of PCD intervention. However, it may prolong the length of ICU stay and the length of hospital stay. It should be worthy of much attention for clinicians.
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Objective To evaluate the clinical effect and safety of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) after hepatectomy.Methods A retrospective analysis of the clinical data of all patients with AKI after hepatectomy for CRRT admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Xi'an Jiaotong University from January 19th, 2013 to January 19th, 2018 was performed. According to the different anticoagulants, the patients were divided into no anticoagulant group (NA group), low molecular heparin anticoagulation (LMHA) group and RCA group. The general data of patients during the perioperative period; renal function, the internal environment, electrolyte and blood coagulation function before and after CRRT; the filter time, the number of filters and adverse events (bleeding, frequent filter blood coagulation, metabolic alkalosis, metabolic acidosis, hypocalcemia, citrate accumulation, etc.) during CRRT were collected. Kaplan-Meier survival curve was used to analyze the life span of the first filter during different anticoagulation. Results A total of 67 cases were included in this study, including 11 in the NA group, 25 in the LMHA group and 31 in the RCA group. There was no significant difference in gender, age, underlying disease, etiology (tumor), Child-Pugh stage (A or B), CT angiography (CTA), basic renal function [serum creatinine (SCr), cystatin C (Cys C)], the American Society of Anesthesiologists (ASA) stage; surgical approach; intraoperative bleeding volume, blood transfusion, blood pressure, time of duration of low blood pressure; and postoperative circulatory failure, hepatic insufficiency and sepsis among three groups. However, the length of ICU stay in RCA group was significantly less than the LMHA group and NA group (days: 8.16±2.24 vs. 10.48±5.11, 13.29±6.64, bothP< 0.05). Compared with before CRRT, the levels of SCr, Cys C and Lac were significantly decreased in RCA group and LMHA group after CRRT [SCr (μmol/L): 89.02±21.90 vs. 248.30±55.32, 105.10±49.00 vs. 270.10±156.00; Cys C (mg/L): 2.18±0.95 vs. 2.94±1.26, 2.26±0.76 vs. 3.07± 0.90; Lac (mmol/L): 2.21±1.46 vs. 3.62±1.73, 2.37±1.24 vs. 4.03±1.69, allP < 0.05]; in addition, LMHA group and NA group had significant effects on hemoglobin (Hb), platelet count (PLT) and activated partial thromboplastin time (APTT) after CRRT [Hb (g/L): 85.4±5.1 vs. 99.6±23.6, 80.0±7.6 vs. 101.4±7.8; PLT (×109/L): 27.60±8.22 vs. 62.04±16.49, 21.36±3.91 vs. 61.45±17.69; APTT (s): 63.07±10.25 vs. 41.52±3.65, 49.56±5.77 vs. 41.09± 3.45, allP < 0.05]; at the same time, Cys C level and prothrombin time (PT) in the NA group after CRRT treatment were significantly increased compared with the others [Cys C (mg/L): 3.59±0.64 vs. 2.29±0.51, PT (s): 26.41±2.43 vs. 23.64±1.92 , bothP < 0.05]. Finally, the time of filters (hours: 60.52±8.82, 31.04±7.03, 13.73±6.26,F = 183.412, P < 0.001) and the number of filter during treatment (number: 2.03±0.60, 3.12±0.73, 4.64±1.29,F = 45.933,P <0.001) in the RCA group, LMHA group and NA group had statistically significant difference. Meanwhile, the incidence of adverse events such as bleeding (0 vs. 4, 7,χ2 = 23.961,P < 0.001) and frequent filter coagulation (1 vs. 10, 11,χ2 =35.413,P < 0.001) in RCA group was significantly lower than that in LMHA group and NA group. Kaplan-Meier survival analysis showed that the life time of the first filter in RCA group was significantly longer than that in LMHA group and NA group (χ2 = 139.45,P < 0.05).Conclusion The application of RCA in patients with AKI after hepatectomy during CRRT is safe and effective, which can significantly prolong the life of the filter and reduce the risk of bleeding.
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Objective To investigate the risk factors and prognosis of acute kidney injury (AKI) after orthotopic liver transplantation (OLT).Methods The retrospective case-control study was conducted.The clinical data of 127 patients who underwent OLT in the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2015 were collected.Of 127 patients,24 were complicated with postoperative AKI,including 17 in grade 1,5 in grade 2 and 2 in grade 3,and 103 were not complicated with AKI.AKI after OLT was treated according to the diagnostic criteria of AKI from 2012 guidelines of Kidney Disease:Improving Global Outcomes (KDIGO).Observation indicators:(1) risk factors analysis affecting AKI after OLT;(2) comparison of postoperative recovery in patients with different AKI grade;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed up to July 2017.Measurement data with nornal distribution were represented as x±-s,and measurement data with skewed distribution were described as M (range).Univariate analysis was done using the t test and rank sum test.Comparisons of count data and univariate analysis were done using chi-square test or Fisher exact probability.Multivariate analysis was done using the logistic regression model.The survival rate and curve were respectively calculated and drawn by the KaplanMeier method,and Log-rank test was used for survival analysis.Results (1) Risk factors analysis affecting AKI after OLT:results of univariate analysis showed that age,combined hypertension,preoperative Child-Pugh score,preoperative model for end-stage liver disease score (MELD),preoperative hemoglobin,preoperative serum albumin,preoperative blood urea nitrogen,preoperative glomerular filtration rate,preoperative prothrombin time,operation time,inferior vena cava occlusion time,duration of anhepatic phase,volume of intraoperative blood loss,total volume of intraoperative blood transfusion,volumes of intraoperative plasma and red blood cells transfusion,duration of postoperative ICU stay,use time of postoperative vasoactive drugs,time of postoperative mechanical ventilation,cases with postoperative infection,body mass index of donor and donor liver cold-ischemia time were related factors affecting occurrence of AKI after OLT (t =4.154,x2 =8.482,t =5.129,3.694,1.294,9.223,5.418,Z=4.287,t=2.105,5.168,8.182,10.042,Z=1.074,0.664,6.274,3.712,1.289,t=1.056,x2 =10.617,t=2.447,3.371,1.476,P＜0.05).Results of multivariate analysis showed that age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time were independent factors affecting occurrence of AKI after OLT [odds ratio (OR) =0.812,0.866,1.392,1.001,0.516,95％ confidence interval:0.717-0.919,0.751-0.997,1.104-1.755,1.000-1.001,0.282-0.944,P＜0.05].(2) Comparison of postoperative recovery in patients with different AKI grade:cases with complete recovery,partial recovery and chronic renal failure were respectively 14,3,0 in 17 patients with grade 1 of AKI and 3,2,0 in 5 patients with grade 2 of AKI and 0,1,1 in 2 patients with grade 3 of AKI,with a statistically significant difference (x2=14.140,P＜0.05).(3) Follow-up and survival situations:127 patients were followed up for 9-44 months,with a median of 23 months.The 1-year overall survival rate of 127 patients was 95.3％.During the follow-up,22 patients died,including 9 with multiple organ failure,8 with primary disease recurrence and 5 with respiratory complication.The median overall survival time after OLT was 36 months in 24 patients with AKI and 40 months in 103 patients without AKI,with no statistically significant difference (x2=3.033,P＞0.05).Conclusion Age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time are independent factors affecting occurrence of AKI after OLT,and there is better recovery in patients with grade 1 of AKI.
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OBJECTIVE To investigate the effect of arctigenin(ATG) on liver fibrosis in rats induced by carbon tetrachloride(CCl4)and to explore its underlying mechanism. METHODS Sprague-Dawley rats were randomly divided into six groups:vehicle,ATG 3.0 mg · kg-1 group,CCl4 model group,CCl4+ATG 1.0 and 3.0 mg·kg-1 groups,and CCl4+colchicine(COL)0.1 mg·kg-1(toxicity)group. Liver fibrosis was induced by subcutaneous injection of CCl4 in rats for 8 weeks. ATG and colchicine were administrated ig once a day starting from the fifth week after the CCl4 treatment for 4 weeks subsequent. At the end of the study,glutamic pyruvic transaminase (GPT),glutamic oxaloacetic transaminase(GOT),albumin(ALB),and total bilirubin (TBIL) as well as the contents of hydroxyproline (HYP) in liver tissues were measured. Histopathological changes were observed in the liver tissues using hematoxyline-eosin(HE)and Masson’s trichrome staining. The proliferation of hepatic stellate cells (HSC) and expression of cell cycle-related proteins were assayed by indirect immunofluores?cence staining and Western blotting,respectively. RESULTS Compared with CCl4 model group,ATG 1.0 and 3.0 mg · kg-1 improved the liver function by decreasing serum contents of GPT,GOT and TBIL (P<0.05),and increasing serum content of albumin(P<0.05). Histological results indicated that ATG 1.0 and 3.0 mg · kg-1 alleviated liver damage and reduced the formation of fibrous septa. Moreover, ATG 1.0 and 3.0 mg · kg-1 significantly decreased liver HYP when compared with CCl4 model group(P<0.05). In addition,CCl4-induced proliferation of activated HSC was inhibited by ATG 1.0 and 3.0 mg·kg-1, and this was accompanied by down-regulation of cyclin D1,cyclin-dependent kinase(CDK)2,CDK4, and proliferating cell nuclear antigen (PCNA)(P<0.05),and up-regulation of p27kip1 in activated HSC (P<0.05). CONCLUSION ATG can alleviate hepatic injury and fibrosis induced by CCl4,which is probably associated with suppression of the proliferation of activated HSC.
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<p><b>BACKGROUND</b>Von Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.</p><p><b>METHODS</b>An epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.</p><p><b>RESULTS</b>A five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.</p><p><b>CONCLUSIONS</b>The results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.</p>