Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

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.

Objective:To investigate the relationship between chronic obstructive pulmonary disease (COPD) and bone mineral density (BMD) in Chinese male and female adults.Methods:Linear regression models were used to analyze the correlations between COPD and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade concerning bone mineral density indices, including broadband ultrasound attenuation, speed of sound, and stiffness index, based on data from the second resurvey of China Kadoorie Biobank.Results:Among 23 876 participants, the prevalence of COPD was 34.3% (3 130/9 125) in males and 23.2% (3 416/14 751) in females. Compared with healthy males and healthy females, broadband ultrasound attenuation, speed of sound, and stiffness index decreased in males and females with COPD, with β values (95% CI) of -0.87 (-1.37- -0.36), -3.42 (-5.42- -1.43) and -1.53 (-2.34- -0.71) in males and -0.66 (-1.09- -0.23), -2.24 (-3.92- -0.55), -1.06 (-1.71- -0.40) in females, respectively. The decrease was greater in males than females (all P for interaction <0.05). The GOLD grade of COPD was inversely correlated with all the three indices in a dose-response manner (all P for trend <0.001). Subgroup analysis showed that patients with COPD had a greater decrease in BMD in males whose ages were ≥ 60 years, males who were less physically active, and participants who were not overweight or obese. Conclusions:COPD was negatively correlated with bone mineral density. More attention should be paid to the bone mineral density of patients with COPD, especially those with older age, less physical activity, or lower BMI.

Objective:To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2.Methods:The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged ( M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test, χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results:There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675, P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group( P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%, P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups( P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups( P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5, P=0.037). Conclusions:For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.

Objective:To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2.Methods:The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged ( M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test, χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results:There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675, P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group( P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%, P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups( P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups( P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5, P=0.037). Conclusions:For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.

Pancreatic cancer is a highly malignant tumor. PARP inhibitor (PARPI) is the first synthetic antineoplastic drug developed based on the concept of synthetic lethality and has been clinically approved for the treatment of ovarian cancer and breast cancer. Due to specific DNA repair defects, studies have found that tumors with BRCA1/2 germline mutations are sensitive to PARPI, but the specific mechanism of action is still unclear. A number of clinical trials for pancreatic cancer have been carried out. Phase III POLO studies have shown that Olaparib is effective and well tolerated as a maintenance treatment in patients with germline BRCA1/2 mutations and patients with metastatic pancreatic cancer after platinum-based induction chemotherapy. Clinical studies related to combination therapy suggest that the benefit of adding PARPI is likely to come from the maintenance phase of treatment. In general, PARPI has broad prospects in the treatment of pancreatic cancer.

Objective:To investigate the effects of ultrasound-guided bilateral erector spinal plane nerve block on postoperative pain and sleep quality in children with pectus excavatum undergoing Nuss.Methods:From February 2020 to December 2021, 40 children with pectus excavatum undergoing Nuss from Hunan Children′s Hospital were prospectively selected and randomly divided into two groups: group E (group E) with erector spinal muscle plane block combined with general anesthesia and group G (group G) , with 20 patients in each group. After general anesthesia, ultrasound guided plane nerve block of bilateral erector spinal muscles was performed in group E, and general anesthesia with tracheal intubation was performed in group G. The Visual Analogue Scale (VAS) Score were recorded at 2, 6, 12, 24 and 48 hours after surgery; The addition of sufentanil, the time of extubation of post anesthesia recovery room (PACU) and the time of leaving the PACU in each group were recorded; The effective pressure times of analgesic pump and the number of people for remedial analgesia were recorded. Pittsburgh sleep quality index (PSQI) was used to score the sleep quality of children before and 2 days after surgery. The occurrence of hypoxemia and restlessness after extubation, nausea and vomiting, pneumothorax, local anesthetic poisoning and other complications were recorded.Results:The VAS score of group E at 2, 6, 12 and 24 hours after operation was lower than that of group G (all P<0.05). There was no significant difference in VAS score 48 hours after operation between the two groups ( P>0.05). The time of decannulation and recovery of PACU in group E was shorter than that in group G (all P<0.05). Compared with group G, there were fewer cases of sufentanil added in group E during operation, and the number of analgesia pump pressing times and cases of postoperative remedial analgesia in group E were less than those in group G (all P<0.05). The PSQI score of sleep quality index 2 days after operation in group E was better than that in group G ( P<0.05). The incidence of hypoxemia, restlessness, nausea and vomiting in group E was lower than that in group G (all P<0.05). Conclusions:Ultrasound-guided bilateral erector spinal nerve block can effectively reduce postoperative pain and complications of NUSS in children with pectus excavatum, and can also reduce the amount of sufentanil used during the operation, improve the sleep quality after the operation, which is conducive to the recovery of children, and is worthy of promotion.

Objective To investigate the expression of S100A16 in pancreatic cancer and its clinical significance. Methods Immunohistochemical experiment was used to detect the expression of S100A16 protein in pancreatic cancer tissues and adjacent tissues, and we analyzed the relation between S100A16 positive expression and clinicopathological parameters, prognosis of pancreatic cancer patients. PPI was used to predict a protein relationship network that directly interacted with S100A16. Results The positive rate of S100A16 expression in cancer tissues was significantly higher than that in adjacent tissues (P=0.001). S100A16 expression was higher in patients with vascular infiltration and lymph node metastasis. The overall survival time of patients with pancreatic cancer was related to tumor size, TNM stage and S100A16 expression level. Multivariate analysis showed that the expression level of S100A16 was an independent risk factor for the prognosis of pancreatic cancer patients, and the risk of death in patients with high S100A16 expression increased by 1.5 times. PPI predicted that S100A16 and S100A14, IL36G, PITX1, PERP played an important role in the interaction network. Conclusion Pancreatic cancer patients with high S100A16 expression have poor prognosis. The positive expression of S100A16 is an independent prognostic indicator.

Objective:To investigate the experience of moderate hypothermia(28℃) using in Stanford A aortic dissection.Methods:A retrospective analysis of 100 patients with Stanford A aortic dissection from January 2012 to March 2014, including 50 cases with deep(25℃) hypothermic circulatory surgery and 50 moderate(28℃) hypothermic circulatory surgery. The operation was performed with ascending aortic replacement, inclusiong aortic arch angioplasty, and stent implantation with descending aorta stent. The difference between the 2 groups during and after the operation was compared.Results:2 cases died in the hypothermia group, and 3 cases died in the deep hypothermia group. There were significant differences( P<0.05) between the middle and low temperature groups in the cooling time, the time of stopping circulation, the time of rewarming, the time of cardiopulmonary bypass, the time of operation, the time of operation, the time of conscious, the time of mechanical ventilation and the first day after the operation( P<0.05), but there was no significant difference between the creatinine and the bilirubin( P>0.05). Conclusion:Under the condition of sufficient cerebral perfusion and spinal cord protection, moderate hypothermia is safe, and it can reduce the operation time and postoperative complications. It has certain clinical significance.