Application status and prospect of biodegradable polymer stents in pancreatobiliary disease / 中华肝胆外科杂志

Endoscopic stent implantation is one of the main methods for the treatment of biliary and pancreatic diseases. At present, the commonly used biliary and pancreatic stents are mainly plastic and metal stents which are still have some deficiencies in clinical applications, and the emergence of the new type of biodegradable polymer materials is expected to achieve the purpose of treatment to overcome these shortcomings. It is a potential hope to break through the bottleneck of endoscopic treatment of choleopancreatic diseases. Previous animal experiments and human clinical studies have preliminarily shown its safety and effectiveness, which can effectively solve some problems of bile and pancreatic duct stenosis and so on. Biodegradable polymer stents have been widely studied, but their clinical application progress is slow and not yet popular, and it has gradually become a research hotspot in recent years . This article discusses the research status and development direction of biodegradable polymer stents in biliary and pancreatic diseases.

Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model / 中华消化外科杂志

Objective:To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.Methods:The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation. Results:(1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them ( Z=?3.636, ?2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone ( odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280?7.519, 1.886?21.080, 1.457?9.265, 1.984?22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone ( odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386?9.723, 2.332?34.006, 1.902?26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone ( odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789?0.988, 1.062?27.071, 1.590?18.827, 2.064?38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813?0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit ( χ2=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability. Conclusions:Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.

Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases / 中华消化外科杂志

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Development of the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability.@*METHODS@#This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability.@*RESULTS@#STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.@*CONCLUSION@#The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.

Influencing factors for endoscopic retrograde cholangiopancreatography-related adverse events in novice trainees and establishment of its prediction model: a prospective study / 中华消化外科杂志

Objective:To investigate the influencing factors for endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events in novice trainees and establishment of its prediction model.Methods:The prospective study was conducted. The clinical data of 12 novice trainees of ERCP in the First Hospital of Lanzhou University from July 2016 to July 2019 were selected. The operation was performed by 12 novice trainees of ERCP under the guidance of the endoscopic experts. Observation indicators: (1) ERCP-related adverse events in novice trainees; (2) analysis of influencing factors for ERCP-related adverse events in novice trainees; (3) establishment of a prediction model for ERCP-related adverse events in novice trainees. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M(range), and com-parison between groups was analyzed by the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. The Logistic regression model was used for univariate and multivariate analyses. The regression coefficients were used to construct a prediction model. The receiver operating characteristic curve was drawn, and the area under curve was used to evaluate the predictive ability. Results:(1) ERCP-related adverse events in novice trainees. Of the 300 patients with ERCP operated by 12 novice trainees, 52 cases had ERCP-related adverse events and 248 cases had no ERCP-related adverse events. Cases in grade 1?2 or grade 3?4 of ERCP difficulty classification, score for intubation time, score for cannulation time, cases with or without completion of the cannulation, cases with or with-out basket stone removal, cases with or without stenosis expansion, score for contrast-enhanced interpretation, score for implementation of reasonable treatment and score for expected purpose reached were 22, 30, 8(range, 5?10), 20(rang, 9?20), 24, 28, 11, 41, 0, 52, 39±17, 39±19 and 44±23 for novice trainees with ERCP-related adverse events, versus 146, 102, 6(range, 4?9), 12(range, 8?20), 163, 85, 94, 154, 20, 228, 52±22, 80±20, 52±23 for novice trainees without ERCP-related adverse events, showing significant differences in the above indicators between them ( χ2=4.79, Z=?2.46, ?2.72, χ2=7.01, 5.30, 4.49, t=?4.00, ?2.97, ?2.29, P<0.05). (2) Analysis of influencing factors for ERCP-related adverse events in novice trainees. Results of univariate analysis showed that the diffi-culty classification of ERCP, intubation time, cannulation time, completion of cannulation, basket stone extraction, contrast-enhanced interpretation, implementation of reasonable treatment and expected purpose reached were related factors for ERCP-related adverse events in novice trainees ( odds ratio=1.95, 1.11, 1.08, 0.45, 0.44, 0.97, 0.98, 0.98, 95% confidence intervals as 1.07?3.58, 1.02?1.22, 1.02?1.14, 0.24?0.82, 0.22?0.90, 0.96?0.99, 0.96?0.99, 0.97?1.00, P<0.05). Results of multi-variate analysis showed that difficulty classification of ERCP and contrast-enhanced interpretation were independent influencing factors for ERCP-related adverse events in novice trainees ( odds ratio=2.08, 0.95, 95% confidence intervals as 1.10?3.96, 0.92?0.99, P<0.05). (3) Establishment of a predic-tion model for ERCP-related adverse events in novice trainees. According to the important outcome indicators of clinical training and results of multivariate analysis, 4 indicators including difficulty classification of ERCP, intubation time, cannulation time and contrast-enhanced interpretation were included to establish a prediction model for ERCP-related adverse events in novice trainees, which indicated that trainees with the predicted score >0.4 were in high risk of ERCP-related adverse events. The area under receiver operating characteristic curve of the prediction model was 0.72(95% confidence interval as 0.65?0.79, P<0.05), with the best cut-off value as 0.40, the sensitivity as 76.9% and the specificity as 63.3%. Conclusion:The difficulty classification of ERCP and contrast-enhanced interpretation are independent influencing factors for ERCP-related adverse events in novice trainees. Novice trainees with a predicted score >0.4 are high-risk groups of ERCP-related adverse events.

The influence of glucose regulatory protein 78 on prognosis and tumor cell proliferation of hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the influence of glucose regulatory protein 78 (GRP78) on prognosis and tumor cell proliferation of hepatocellular carcinoma.Methods:The experimental study and retrospective cohort study were conducted. Based on hepatocellular carcinoma tissue chip, in vitro culture of Huh7 and Hep3B hepatoma cells and LO2 normal hepatic cell, and combined with immunohistochemical staining, cell transfection, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot detection, cell proliferation experiments, cell clone formation experiments and high-throughput transcription histological analysis, the GRP78 expression in hepatoma cells was analyzed. Huh7 and Hep3B hepatoma cells being transfected with the GRP78 gene-specific shRNA lentiviruses or the negative control shRNA lentivirus were set as the GRP78 gene-specific shRNA lentivirus group and the negative control shRNA lentivirus group respectively. Observation indicators: (1) GRP78 expression in hepatocellular carcinoma tissue and adjacent tissue and its correlation with the clinicopathological characteristics of hepatocellular carcinoma patients; (2) analysis of factors affecting the prognosis of hepatocellular carcinoma patients; (3) effects of inhibiting of GRP78 expression on the proliferation of hepatoma cells; (4) effects of inhibiting of GRP78 expression on the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells; (5) effects of HA15 on the proliferation and the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells. Measurement data of the normal distribution were expressed as Mean± SD, and comparison of groups was conducted using the t test or ANOVA. Repeated measurement data were analyzed using repeated ANOVA. Count data were expressed as absolute numbers, and comparisons between groups was conducted using the chi-square test. COX proportional hazards regression model was used for univariate and multivariate analysis. The Kaplan-Meier method was used to calculate the survival time and draw survival curve, and the Log-rank test was used for generative analysis. Results:(1) GRP78 expression in hepatocellular carcinoma tissue and adjacent tissue and its correlation with the clinicopathological characteristics of hepatocellular carcinoma patients: results of immunohistochemical staining of hepatocellular carcinoma tissue chip showed that GRP78 was low-expressed in 53 cases and high-expressed in 37 cases of the 90 hepatocellular carcinoma tissues. GRP78 was low-expressed in 84 cases and high-expressed in 6 cases of the 90 paracancerous tissues. There was a significant difference in GRP78 expression between hepatocellular carcinoma tissues and paracancerous tissues ( P<0.05). (2) Analysis of factors affecting the prognosis of hepatocellular carcinoma patients: all 90 patients were followed up for 5 to 56 months, with a median follow-up time of 49 months. The median overall survival time and median disease progression-free survival time were 56 months and 53 months in the 53 hepatocellular carcinoma patients with GRP78 as low-expressed, versus 32 months and 19 months in the 37 hepatocellular carcinoma patients with GRP78 as high-expressed, respec-tively, showing significant differences ( χ2=17.482, 12.097, P<0.05). Results of univariate analysis showed that alanine aminotransferase (ALT), tumor pathological grading and GRP78 expression were related factors affecting the 3-year overall survival rate and disease progression-free survival rate of hepatocellular carcinoma patients ( hazard ratio=2.317, 2.039, 3.740 and 2.194, 2.177, 2.927, 95% confidence interval as 1.150?4.671, 1.201?3.462, 2.116?6.612 and 1.048?4.593, 1.093?4.336, 1.492?5.742, P<0.05). Results of multivariate analysis showed that ALT >40 U/L, tumor pathological grading as Ⅲ-Ⅳ grade and GRP78 as high-expressed were independent risk factors affecting the 3-year overall survival rate and disease progression-free survival rate of hepatocellular carcinoma patients ( hazard ratio=2.438, 2.245, 3.223 and 3.046, 2.473, 3.307, 95% confidence interval as 1.114?5.334, 1.047?4.814, 1.396?7.440 and 1.337?6.940, 1.141?5.360, 1.399?7.819, P<0.05). (3) Effects of inhibiting of GRP78 expression on the proliferation of hepatoma cells: ①results of qRT-PCR showed that the relative expression of GRP78 messenger RNA (mRNA) in Huh7, Hep3B, and LO2 cells were 3.06±0.33, 4.42±0.60 and 1.00±0.02. There were significant differences in GRP78 mRNA expression between Huh7 and LO2 cells or Hep3B and LO2 cells ( t=6.19, 5.42, P<0.05). ②Results of Western Blot detection showed that the relative expression of GRP78 protein in Huh7, Hep3B, and LO2 cells were 1.65±0.01, 1.77±0.01 and 0.99±0.02. There were significant differences in GRP78 protein expression between Huh7 and LO2 cells or Hep3B and LO2 cells ( t=75.09, 108.10, P<0.05). ③Results of cell proliferation experiments showed that the growth rates in Hu7 GRP78 gene-specific shRNA lentiviruses group cells and Hu7 negative control shRNA lentivirus group cells at 24, 48, 72 and 96 hours were 111.51%±0.35%, 144.85%±0.68%, 188.71%±3.62%, 282.51%±5.25% and 190.08%±0.58%, 285.76%±2.69%, 459.51%±4.29%, 597.88%±12.25%, showing signifi-cant differences ( Fgroups=1 360.000, Ftime=668.500, Finteraction=197.600, P<0.05). The growth rates in Hep3B GRP78 gene-specific shRNA lentiviruses group cells and Hep3B negative control shRNA lentivirus group cells at 24, 48, 72 and 96 hours were 124.47%±0.25%, 153.25%±1.25%, 195.45%±3.19%, 282.51%±10.76% and 179.69%±0.33%, 322.67%±2.46%, 486.27%±5.82%, 622.35%±12.58%, showing significant differences ( Fgroups=1 222.000, Ftime=706.200, Finteraction=179.600, P<0.05). ④Results of the cell clone formation experiments showed that the number of cells in Hu7 GRP78 gene-specific shRNA lentiviruses group cells and Hu7 negative control shRNA lentivirus group cells were 125±3 and 435±17, showing a significant difference ( t=17.86, P<0.05). The number of cells in Hep3B GRP78 gene-specific shRNA lentiviruses group cells and Hep3B negative control shRNA lentivirus group cells were 138±3 and 388±7, showing a significant difference ( t=32.29, P<0.05). (4) Effects of inhibiting of GRP78 expression on the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells: results of high-throughput transcription histological analysis showed that the relative expression rates of p53, p21, CDK2, CDK4, and CDK6 were 19%, 334%, 398%, 41% and 49% in the Hu7 GRP78 gene-specific shRNA lentiviruses group cells comparing to the Hu7 negative control shRNA lentivirus group cells. ①Results of qRT-PCR showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.17±0.03, 4.05±0.71, 3.73±0.47, 0.49±0.09, 0.48±0.06, 0.36±0.07 in the Hu7 GRP78 gene-specific shRNA lentiviruses group cells, versus 1.00±0.05, 1.03±0.17, 1.00±0.07, 1.01±0.09, 1.02±0.14, 1.00±0.03 in the Hu7 negative control shRNA lentivirus group cells, showing significant differences ( t=14.62, 4.17, 5.72, 4.26, 3.49, 8.82, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.11±0.01, 4.28±0.43, 4.19±0.22, 0.44±0.01, 0.25±0.03, 0.68±0.04 in Hep3B GRP78 gene-specific shRNA lentiviruses group cells, versus 1.01±0.09, 1.02±0.15, 1.00±0.06, 1.01±0.09, 1.01±0.08, 1.15±0.02 in Hep3B negative control shRNA lentivirus group cells, showing significant differences ( t=10.19, 7.14, 13.79, 6.37, 9.42, 9.61, P<0.05). ②Results of Western Blot detection showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.45±0.01, 1.98±0.05, 2.31±0.12, 0.75±0.03, 0.69±0.04, 0.82±0.03 in the Hu7 GRP78 gene-specific shRNA lentiviruses group cells, versus 1.01±0.05, 1.03±0.01, 1.00±0.02, 1.00±0.01, 1.01±0.02, 1.00±0.03 in the Hu7 negative control shRNA lentivirus group cells, showing significant differences ( t=11.07, 14.56, 11.30, 11.29, 10.55, 11.37, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.61±0.03, 1.98±0.16, 2.55±0.12, 0.85±0.03, 0.78±0.01, 0.54±0.02 in Hep3B GRP78 gene-specific shRNA lentiviruses group cells, versus 1.00±0.03, 1.05±0.02, 1.05±0.01, 1.05±0.02, 1.00±0.02, 1.00±0.02 in Hep3B negative control shRNA lentivirus group cells, showing significant differences ( t=10.97, 13.40, 12.35, 11.06, 12.45, 13.78, P<0.05). (5) Effects of HA15 on the proliferation and the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells: results of 50% inhibiting concentration (IC50) test of HA15 showed that the IC50 of HA15 for Huh7 and Hep3B cells at 48 hours were 9.98 μmol/L and 13.70 μmol/L. ①Huh7 and Hep3B cells were treated with 9.98 μmol/L and 13.70 μmol/L of HA15. Results of cell proliferation experiments showed that the growth rates at 24, 48, 72, and 96 hours were 112.81%±0.27%, 154.71%±1.45%, 237.66%±16.77%, 294.40%±14.92% in the HA15-Huh7 cells, versus 133.67%±0.49%, 352.93%±2.31%, 557.17%±4.89%, 662.60%±13.31% in the normal Huh7 cells, showing a significant difference ( Fgroups=766.800, Ftime=518.200, Finteraction=133.300, P<0.05). The growth rates at 24, 48, 72, and 96 hours were 121.27%±2.32%, 203.85%±3.18%, 240.80%±3.02%, 286.50%±7.10% in the HA15-Hep3B cells, versus 239.14%±1.02%, 362.00%±5.44%, 539.37%±10.80%, 694.79%±17.13% in the normal Hep3B cells, showing a signifi-cant difference ( Fgroups=594.300, Ftime=317.900, Finteraction=78.600, P<0.05). ②Results of qRT-PCR showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.27±0.05, 3.64±0.28, 4.13±0.41, 0.51±0.07, 0.39±0.03, 0.17±0.02 in the HA15-Huh7 cells, versus 1.02±0.14, 1.00±0.03, 1.00±0.05, 1.01±0.08, 1.01±0.09, 1.03±0.17 in the normal Huh7 cells, showing significant differences ( t=5.00, 9.25, 7.63, 4.73, 6.82, 5.01, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.28±0.03, 3.49±0.78, 4.31±0.53, 0.38±0.05, 0.36±0.04, 0.24±0.03 in the HA15-Hep3B cells, versus 1.01±0.11, 1.03±0.18, 1.01±0.08, 1.00±0.06, 1.02±0.15, 1.00±0.06 in the normal Hep3B cells, showing significant differences ( t=6.26, 3.08, 6.21, 7.97, 4.26, 11.08, P<0.05). ③Results of Western Blot detection showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.52±0.05, 1.94±0.08, 1.58±0.02, 0.89±0.00, 0.86±0.02, 0.74±0.01 in the HA15-Huh7 cells, versus 1.02±0.03, 1.00±0.03, 1.02±0.02, 1.04±0.03, 1.00±0.01, 1.01±0.02 in the normal Huh7 cells, showing significant differences ( t=11.54, 10.28, 11.03, 12.81, 13.67, 10.09, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.57±0.02, 1.67±0.04, 1.41±0.04, 0.82±0.03, 0.70±0.02, 0.74±0.01 in the HA15-Hep3B cells, versus 1.03±0.01, 0.98±0.03, 1.00±0.03, 1.03±0.03, 1.01±0.01, 1.04±0.01 in the normal Huh7 cells, showing significant differences ( t=10.81, 11.54, 12.26, 13.62, 14.23, 10.17, P<0.05). Conclusions:High expression of GRP78 is an independent risk factor affecting the overall survival and disease progression-free survival of hepatocellular carcinoma patients. Inhibiting of GRP78 expression can reduce cell proliferation and the expression of p53, p21, CDK2, CDK4, and CDK6 mRNA and proteins in hepatoma cells.

Early mobilization on mortality of patients with mechanical ventilation in intensive care unit after discharge: a Meta-analysis / 中华危重病急救医学

Objective:To evaluate the effect of early mobilization on mortality in intensive care unit (ICU) patients with mechanical ventilation after discharge by Meta-analysis.Methods:Databases including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang data, PubMed, the Cochrane Library, Web of Science, and Embase were searched from inception to September 17th, 2020, to collect randomized controlled trials (RCT) about early mobilization on mortality of patients with mechanical ventilation in ICU after discharge, the references included in the literature were traced. The control group was given routine care, the experimental group was given early mobilization on the basis of the control group, including passive or active mobilization on the bed, sitting on the bed, standing by the bed, transferring to the bedside chair and assisting walking. The literature screening, data extracting, and the bias risk assessment of included studies were conducted independently by two reviewers. Stata 12.0 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 10 RCT studies involving 1 323 patients were included, with 660 patients in the control group and 663 patients in the experimental group. The results of literature quality evaluation showed that 7 studies were grade A and 3 studies were grade B, indicating that the overall quality of included literatures was high. The Meta-analysis results showed that early mobilization did not increase the mortality of patients with mechanical ventilation in ICU after discharge [odds ratio ( OR) = 0.92, 95% confidence interval (95% CI) was 0.75-1.13, P = 0.449]. Subgroup analysis results showed that early mobilization had a tendency to reduce the mortality of ICU patients with mechanical ventilation at 3, 6 and 12 months after discharge, but the difference was not statistically significant (3-month mortality: OR = 1.02, 95% CI was 0.74-1.40, P = 0.927; 6-month mortality: OR = 0.95, 95% CI was 0.70-1.27, P = 0.712; 12-month mortality: OR = 0.60, 95% CI was 0.33-1.10, P = 0.101). Funnel plot showed that the distribution of included literatures was not completely symmetrical, suggesting that publication bias might exist. Conclusions:Early mobilization does not increase the mortality of ICU patients with mechanical ventilation after discharge. Although it tends to have a favorable outcome in reducing mortality, and has a trend to reduce the mortality. However, due to the small number of included literatures, small sample size and differences in the specific implementation of early mobilization among various studies, a large number of high-quality RCT studies are still needed for further verification.

Evaluation of pharmaceutical prevention and treatment of intensive care unit-acquired weakness: a Meta-analysis / 中华危重病急救医学

Objective:To evaluate the effect of preventing and treatment of pharmaceuticals on intensive care unit-acquired weakness (ICU-AW) by systematic review.Methods:The randomized controlled trials (RCTs) concerning pharmaceutical prevention and treatment about ICU-AW in SinoMed, CNKI, Wanfang data, PubMed, Cochrane Library, Web of Science, EMbase, and other sources were searched from their foundation to May 30th, 2019. The patients in the intervention group were treated with drugs to prevent or treat ICU-AW; and those in control group were treated with other rehabilitation methods. Data searching, extracting and quality evaluation were assessed by two reviewers independently. Stata 12.0 software was then used for Meta-analysis. Only descriptive analysis was conducted when only one study was enrolled.Results:A total of 11 RCTs were enrolled with 1 865 patients in the intervention group and 1 894 in the control group. The results of quality evaluation showed that 4 studies were A-level and 7 studies were B-level, indicating that the overall quality of the enrolled literature was high. Meta-analysis showed that intensive insulin therapy could prevent ICU-AW [relative risk ( RR) = 0.761, 95% confidence interval (95% CI) was 0.662-0.876, P = 0.000], but reduced phenylalanine loss (nmol·100 mL -1·min -1: -3±3 vs. -11±3, P < 0.05) and glutamine intake (nmol·100 mL -1·min -1: -97±22 vs. -51±13, P < 0.05). There was no significant difference in the prevention and treatment of ICU-AW between other drugs (including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin) and control group. Conclusions:Intensive insulin therapy can prevent ICU-AW, but the risk of hypoglycemia will increase. Other drugs including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin have no obvious advantages in the prevention and treatment of ICU-AW, so no drug has been recommended to prevent and treat ICU-AW.

Selection of endoscopic stents for type Ⅳ hilar cholangiocarcinoma / 中华消化内镜杂志

Objective:To determine a better treatment and endoscopic stent for type Ⅳ hilar cholangiocarcinoma.Methods:Clinical data of 65 patients diagnosed with type Ⅳ hilar cholangiocarcinoma at Department of General Surgery, the First Hospital of Lanzhou University from September 2010 to September 2018 were retrospectively analyzed. According to different endoscopic drainage methods, the patients were divided into three groups, endoscopic retrograde biliary drainage (ERBD) group (n=38), ERBD + endoscopic metal biliary endoprosthesis (EMBE) group (n=23) and EMBE group (n=4). According to different contrast methods, patients were divided into the contrast media group (n=26), air contrast group (n=22) and non-contrast group (n=17). Incidence of postoperative acute cholangitis, incidence of bilirubin levels decline and in-hospital mortality were analyzed.Results:The incidences of acute cholangitis in ERBD group, ERBD+ EMBE group and EMBE group were 23.7% (9/38), 52.2% (12/23) and 75.0% (3/4), respectively, with significant differences ( χ2=7.499, P=0.006). The in-hospital mortalities of the above three groups were 5.3% (2/38), 13.0% (3/23) and 50.0% (2/4), respectively, with significant differences ( χ2=7.729, P=0.021). For pairwise comparisons, there was significant difference in in-hospital mortalities between ERBD group and EMBE group ( χ2=8.406, P=0.004). The incidences of acute cholangitis were 57.7% (15/26), 27.3% (6/22) and 17.6% (3/17), respectively, in the contrast media group, the air contrast group and the non-contrast group, with significant difference ( χ2=8.407, P=0.015). For pairwise comparisons, there was significant difference in acute cholangitis incidence between the contrast media group and the non-contrast group ( P=0.012). Conclusion:For type Ⅳ hilar cholangiocarcinoma, biliary double plastic stent implantation can significantly reduce the incidence of postoperative acute cholangitis and the mortality during hospitalization, which can be used as the preferred stent scheme. Additionally, intraoperative contrast agents may increase the incidence of postoperative acute cholangitis which should be used with caution.

Effectiveness and safety of epinephrine and norepinephrine for treating non-variceal upper gastrointestinal bleeding: a meta-analysis / 中华消化内镜杂志

Objective:To systematically evaluate the effectiveness and safety of epinephrine injection and norepinephrine spraying for treating non-variceal upper gastrointestinal bleeding.Methods:Databases including the PubMed, Embase, Cochrane Library, CNKI, CBM, VIP and WanFang Data with the retrieval time from inception to December 2018 were searched to collect the related clinical trials. The references of included studies were also retrieved. Studies were screened, data were extracted, and the risk of bias was assessed by 2 reviewers separately. The meta-analysis was conducted by using RevMan 5.3 software. The grading of recommendations, assessment, development and evaluation (GRADE) quality of evidence system was used to assess the results of meta-analysis.Results:A total of 10 studies involving 884 participants were included. The results showed that compared with the norepinephrine spraying, epinephrine injection was superior in the following aspects with significant differences: the effective rate ( RR=1.21, 95% CI: 1.12-1.30, P<0.001); the one-week recurrent bleeding rate ( RR=0.28, 95% CI: 0.17-0.45, P<0.001); the immediate hemostatic rate ( RR=1.38, 95% CI: 1.25-1.52, P<0.001); and the emergent operation rate ( RR=0.35, 95% CI: 0.19-0.63, P<0.001). Conclusion:Epinephrine injection is more effective and safer for treating non-variceal upper gastrointestinal bleeding in comparison with norepinephrine spraying.

Value of radiography with CO2 combined with contrast agents in endoscopic drainage for hilar cholangiocarcinoma / 中华消化内镜杂志

Objective To evaluate radiography with CO2 combined with contrast agents for endoscopic drainage of unresectable hilar cholangiocarcinoma. Methods Clinical data of 43 patients with unresectable hilar cholangiocarcinoma undergoing endoscopic drainage at the First Hospital of Lanzhou University from October 2010 to October 2015 were analyzed retrospectively. According to different contrast agents in radiography, patients were divided into the study group ( CO2 combined with contrast agent) and the control group ( contrast agent alone) . There were 23 cases in the study group and 20 cases in the control group. Total postoperative bilirubin(TBIL),white blood cell(WBC),procalcitonin(PCT)and the incidence of complications in the two groups were compared. Results The endoscopic procedure ranged from 50 min to 70 min. TBIL, WBC, PCT at 48 h and 72 h after operation in the study group were lower than those in the control group[48 h TBIL:(173. 42±66. 78) μmol/L VS (210. 81±78. 34) μmol/L,P=0. 025;72 h TBIL:(104. 64±56. 35) μmol/L VS (159. 33±59. 59) μmol/L, P=0. 023; 48 h WBC:(11. 51±7. 78)×109/L VS (15.83±6.67)×109/L, P=0.026; 72 h WBC:(10.92±5.64)×109/L VS (14.72±4.97)×109/L, P=0. 026; 48 h PCT:(0. 56±0. 18) ng/mL VS (1. 24±0. 73) ng/mL, P=0. 003; 72 h PCT:(0. 42± 0. 27) ng/mL VS (0. 90±0. 20) ng/mL, P=0. 001]. The incidence of postoperative cholangitis in the study group was lower than that in the control group [ 13. 0％( 3/23) VS 40％( 8/20) , P=0. 043] . Relatively low incidence of postoperative pancreatitis occurred in both groups, with no significant difference [ 4. 3％( 1/23) VS 10. 0％(2/20),P=0. 090]. Conclusion Radiography with CO2 combined with contrast agents during endoscopic drainage procedures for unresectable hilar cholangiocarcinoma is safe and effective, which could lower incidence of postoperative cholangitis.

Emergency endoscopic treatment of acute obstructive suppurative cholangitis / 中华消化内镜杂志

Objective To determine the best endoscopic treatment for acute obstructive suppurative cholangitis (AOSC).Methods Data of 93 patients who were diagnosed as having AOSC in endoscopic center in the last three years were retrospectively analyzed.All patients were divided into three groups according to the different treatment methods:ENBD group,ENBD+ERBD group and double ERBD group.Postoperative temperature,bilirubin levels and mortality were compared.Results For patients with high level obstruction,incidence of fever in ENBD+ERBD group and double ERBD group were significantly higher than that of ENBD group (1/18 VS 4/10,P ＜ 0.05;0 VS 4/10,P ＜ 0.05).There were no significant differences in incidence of fever(1/18 VS 0) or bilirubin level decrease (17/18 VS 14/15) between ENBD+ERBD group and double ERBD group.For high level obstruction,if the patient had biliary imaging with contrast medium during operation,they would have higher incidence of high fever[(4/10 VS 3.45％ (1/28)] and mortality(3/11 VS 0),lower declining rate of bilirubin level [10/14 VS 96.55％(28/29)] than those without.Conclusion Both left and right hepatic ducts drainage should be recommended for high level biliary obstruction.During the operation,contrast medium should be limited to minimum dose,and should be avoided in high level obstruction cases.Air biliary imaging could be used when necessary.

Early endoscopic pancreatic and (or) biliary stents combined with Qingyi granules in treatment of acute biliary pancreatitis / 中华内分泌外科杂志

Objective To investigate the early (within 72 hours) application and effect of endoscopic pancreatic and (or) biliary stents combined with Qingyi granules in treatment of acute biliary pancreatitis (ABP) patients.Methods A retrospective analysis was done to the 245 patients admitted for ABP from Jan.2012 to Jan.2016 in the First Hospital of Lanzhou University.133 patients (group A) were treated within 72 hours by endoscopic pancreatic and (or) biliary stents combined with Qingyi granules through feeding tube.112 patients (group B) were treated by endoscopic pancreatic and (or) biliary stents and feeding tube without Qingyi granules.Then the study was done to compare the difference of recover days of abdominal distension,abdominal pain,normalization time of amylase and WBC,length of stay,decrease level of PCT,and the incidence of ABP complications.Results Group A was superior to group B in terms of the recover days of abdominal distension (3.8±3.2)d vs (5.2± 2.4)d,abdominal pain (2.6±2.1)d vs (4.9±2.7)d,normalization time of amylase(2.8±1.6)d vs (4.4±3.7)d,WBC (2.6±1.3)d vs (4.1± 2.7)d,length of stay(9.4±2.1)d vs (12.6±3.3)d and postoperative PCT level(2.59±2.33)ng/ml vs (3.98±3.03)ng/ml,and the difference had statistical significance (P＜0.05),while there was no significant difference between the two groups in the incidence of ABP complications.Conclusions For ABP patients,early placement of endoscopic pancreatic and (or) biliary duct stents combined with Qingyi granules through feeding tube can remove the etiology,and block the disease from further progress.Early enteral nutrition can contribute to the recovery of intestinal mucosa and the maintenance of internal environment.Combined with Qingyi granules,it can relief the symptoms,decrease the laboratory index and shorten the hospitalization time.

Efficacy of endoscopy for the treatment of benign biliary stricture after biliary surgery / 中华消化外科杂志

Objective To investigate the efficacy of endoscopy for the treatment of benign biliary stricture after biliary surgery.Methods The clinical data of 127 patients with benign biliary stricture after biliary surgery at the First Hospital of Lanzhou University from January 2007 to December 2011 were retrospectively analyzed.According to the Bismuth classification,there were 60 patients with type Ⅰ,35 with type Ⅱ,21 with type Ⅲ and 11 with type Ⅳ.The efficacies of endoscopy for the treatment of biliary stricture with different Bismuth subtypes were analyzed.Results The location and severity of biliary stricture were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) + cholangiography.Sixteen patients ( including 7 with type Ⅲ and 9 with type Ⅳ) were transferred to surgical treatment due to severe biliary stricture.A total of 111 patients underwent endoscopic treatment successfully,with the success rate of 87.4％ (111/127).The success rates of endoscopy for the treatment of patients with Bismuth Ⅰ,Ⅱ,Ⅲ and Ⅳ biliary strictures were 95％ (57/60),86％ (30/35),9/14and 1/2,respectively.Twenty-nine patients were implanted with retrievable metallic biliary stent,and 82 were implantated with plastic biliary stent.Of the 111 patients,only 6 patients were complicated by acute pancreatitis,and they were cured by conservative treatment.The alleviative rates of yellow skin and icteric sclera,tenderness and distending pain of right upper quadrant,fever were 73％ (81/111 ),83％ (74/89),90％ (73/81 ) and 89％(68/76) at 1 week after treatment,and they were 88％ (98/111),91％ (81/89),94％ (76/81) and 92％(70/76) at 8 weeks after treatment.The efficacy of endoscopy was good in 97 patients and poor in 14 patients,and the 14 patients were converted to open surgery.The symptoms including yellow skin and icteric sclera,tenderness and distending pain of right upper quadrant,fever were completely alleviated at postoperative month 6.Conclusion Endoscopic treatment for benign biliary stricture is safe and effective.

ERCP, laparoscopy and choledochoscopy for Mirizzi syndrome / 中华普通外科杂志

ObjectiveTo investigate the treatment of Mirizzi syndrome (MS) by ERCP、laparoscopy and choledochoscopy. MethodsIn this study 12 cases were confirmed intraoperatively as with MS from July 2005 to June 2009. Patients were treated by ERCP,laparoscopy and choledochoscopy according to the Csendes Classification. ResultThere were 7 MS patients complicating common bile duct stones among all 12 MS cases.There were 8 cases of Type Ⅰ Csendes MS,3 cases of Type Ⅱ and 1case of Type Ⅲ.11cases were treated by the ERCP、laparoscopy and choledochoscope.4 cases was treated by primary closure of common bile duct in laparoscopy,all the patients were cured.The case of type Ⅲ with T tube placed for stone caused bile duct injury had no stricture of the common bile duct as demonstrated by postoperative follow-up cholangiography.ConclusionsERCP,laparoscopy and choledochoscopy are effective for the treatment of Mirizzi syndrome.

Combined application of laparoscope and multiple endoscopes for the treatment of extra-hepatic bile duct stones:a report of 3780 eases / 中华消化外科杂志

Objective To investigate the efficacy of combined application of laparoscope and multiple endoscopes for the treatment of extra-hepatic bile duct stones.Methods The clinical data of 3780 patients with extra-hepatic bile duct stones who were admitted to the First Hospital of Lanzhou University from March 1998 to June 2010 were retrospectively analyzed.According to the condition of bile duct stones,laparoscope,choledochoscope and duodenoscope were applied separately or combinately.All patients were divided into A,B and C groups.Patients in group A were treated by laparoseopy,choledochoscopy or duodenoscopy;patients in group B were treated by choledochoscopy+duodenoscopy.duodenoscopy+laparoscopy or laparoscopy+choledochoscopy;patients in group C were treated by laparoscopy+duodenoscopy+choledochoscopy.The efficacies of different treatment approaches were analyzed by comparing the results of imaging examination and follow-up.Results The curative rate and complication rate of the group A were 89.54%(1276/1425)and 6.73%(86/1276),respectively.Of the 149 patients in the group A who were failed in the treatment,83 patients were transferred to the group B,and 66 patients were transferred to the group C.The curative rate and complication rate of the group B(including 83 patients transferred from the group A)were 95.93%(1719/1792)and 4.07%(70/1719),respectively,and 73 patients who were failed in the treatment were transferred to the group C.The curative rate and complication rate of the group C(including 139 patients transferred from the group C)were 99.75%(783/785)and 0.26% (2/783),respectively,and 2 patients who were failed in the treatment received open surgery.Conclusion Combined application of laparoscope and endoscopes could raise the success rate of stone clearance and decrease the postoperative complications.