Objective: To explore the role of toll-like receptor 4 (TLR4)/NF-κB signaling pathway in acute necrotizing pancreatitis (ANP)-associated lung injury and the intervention of lipoxin A4 (LXA4) analogue. Methods: Forty-five Sprague-Dawley rats were randomly(random number)divided into the sham operation group, experimental group, and intervention group, each group containing 15 rats. ANP animal models were prepared by injecting sodium taurocholate into biliopancreatic tube in the experimental group. No sodium taurocholate was injected into biliopancreatic duct in the sham operation group. After the preparation of ANP animal models in the intervention group, LXA4 was injected through the tail vein. Rats in each group were randomly divided into 3 subgroups (n=5 each subgroup). The serum amylase, TNF- α, IL-1β, IL-6 and endotoxin levels were detected 6, 12 and 24 h after the operation. The lung injury scores were assessed and the lung wet/dry weight ratio was calculated. The expressions of TLR4 and NF-κB p65 in lung tissues were detected by Western blot. Results: Serum levels of amylase, TNF-α, IL-1β, IL-6 and endotoxin in the experimental and intervention groups were significantly higher than those in the sham operation group, while the levels of the above indicators in the intervention group was significantly lower than those in the experimental group, and the differences were statistically significant (P<0.05). Postoperative lung injury scores and lung wet/dry weight ratio in the experimental group were significantly higher than those in the sham operation group, and the differences were statistically significant (P<0.05). Lung injury scores in the intervention group 6 h after operation had no significant difference compared with those in the sham operation group (P>0.05), while lung wet/dry weight ratio in the intervention group 6 h after operation, and lung injury scores and lung wet/dry weight ratio in the intervention group 12 h or 24 h respectively after operation were significantly higher than those in the sham operation group, with statistically significant differences (P<0.05). Postoperative lung injury scores and lung wet/dry weight ratio in the intervention group were significantly lower than those in the experimental group, and the differences were statistically significant (P<0.05). The expressions of TLR4 and p65 in the lung tissues of the experimental and intervention groups were significantly higher than those of the sham operation group, and the expressions of TLR4 and p65 in the lung tissues of the intervention group were significantly lower than those of the experimental group, with statistically significant differences (P<0.05). Conclusions LXA4 can reduce the severity of acute necrotizing pancreatitis-associated lung injury, and its mechanism is related to reducing the stimulation of endotoxin, thus inhibiting TLR4 signaling pathway and the activation of p65 to down-regulate the level of pro-inflammatory cytokines.

Objective:To explore the mechanism of pioglitazone in reducing lung injury induced by acute pancreatitis.Methods:Thirty healthy male SD rats were randomly(random number) divided into the sham operation group, model group and pioglitazone group, with 10 rats in each group. After anesthesia, the rats in the sham operation group were injected with normal saline retrogradely through the pancreaticobiliary duct. In the model group, after anesthesia, the rats were retrogradely injected with sodium taurocholate into the pancreaticobiliary duct to construct the lung injury model of severe acute pancreatitis. In the pioglitazone group, the model was established after intraperitoneal injection of pioglitazone. Six rats in each group were randomly selected and killed 12 h after operation, and then lung tissue and venous blood were collected. The levels of serum amylase and TNF-α and NO in lung tissue homogenate were detected and compared among the three groups; the expression of TLR2 mRNA and TLR4 mRNA in lung tissue was detected by RT-PCR and compared among the three groups; the lung tissue pathological injury score and lung leakage index were calculated and compared among the three groups. The correlation of TLR2 and TLR4’s mRNA expression with lung tissue pathological injury score and lung leakage index was analyzed.Results:The levels of serum amylase and the levels of TNF-α and NO in lung tissue homogenate in the model group were significantly higher than those in the sham operation group, and the above indexes in the pioglitazone group were significantly lower than those in the model group ( P<0.05). The expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue, the lung tissue pathological injury score and lung leakage index in the model group were significantly higher than those in the sham operation group, and the above indexes in the pioglitazone group were significantly lower than those in the model group ( P<0.05). Spearman correlation analysis showed that the expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue were significantly positively correlated with the lung tissue pathological injury score ( rs=0.959, P<0.001; rs=0.924, P<0.001). Pearson correlation analysis showed that the expression levels of TLR2 mRNA and TLR4 mRNA in lung tissue were significantly positively correlated with the lung leakage index ( r=0.957, P<0.001; r=0.958, P<0.001). Conclusions:Pioglitazone may reduce the severity of severe acute pancreatitis induced lung injury by inhibiting the expression of TLR2 mRNA and TLR4 mRNA in lung tissue.

Objective:To explore the mechanism of miR-494 negatively regulating ROCK1 and PTEN in inhibiting apoptosis of pancreatic cells and participating in the occurrence and development of acute pancreatitis.Methods:Pancreatic acinar cells AR42J from rats were treated by caerulein, and then the levels of amylase, tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1) and IL-6 in the supernatant of cell culture were detected by ELISA to verify the cell model of acute pancreatitis. RT-PCR was used to detect the expression of miR-494 in normal AR42J cells (control group) and acute pancreatitis cell model (model group). Flow cytometry was used to detect the apoptosis of the control group, negative control miRNA transfected acute pancreatitis cell model (negative control group) and miR-494 transfected acute pancreatitis cell model (miR-494 transfection group). Western blot was used to detect the expression of ROCK1 and PTEN in the control group, negative control group and miR-494 transfection group.Results:The levels of amylase, TNF-α, IL-1 and IL-6 in the supernatant of AR42J cells treated with caerulein for 8 h and 12 h were significantly higher than those at 0 h and the control group ( P<0.05), indicating that the model was successfully constructed. The expression levels of miR-494 at 8 h, 12 h and 24 h after the establishment of acute pancreatitis cell model were significantly higher than those at 4 h and the control group ( P < 0.05). The apoptosis rate of the model group was significantly higher than that of the control group ( P<0.05), and the apoptosis rate of the miR-494 transfection group was significantly lower than that of the model group ( P<0.05). The expression levels of ROCK1 and PTEN in the miR-494 transfection group were significantly lower than those in the model group and negative control group ( P<0.05). Conclusions:When acute pancreatitis occurs, overexpression of miR-494 can inhibit the expression of pro-apoptotic protein, thus inhibiting the apoptosis of pancreatic acinar cells and promoting the development of acute pancreatitis.

Background and objective Cathepsin X (Cat X) has been identiifed as a member of cathepsin family. Studies have shown that Cat X is involved in tumorigenesis and tumor development of various cancers. hTe aim of this study is to investigate the relationship between the clinicopathological prognosis and the levels of Cat X and cystatin C in the serum of patients with lung cancer. Methods Blood samples were collected from 84 patients with lung cancer and 36 healthy control subjects. Cat X and cystatin C were determined by quantitative ELISA. Results Cat X and cystatin C levels were signiifcantly higher in the patients with lung cancer than that in the healthy control subjects (P<0.01). Cat X level was correlated with the pathological types of lung cancer (P=0.076). Cystatin C was positively correlated with TNM stage (P=0.01). Furthermore, cystatin C/Cat X was correlated with lymph node metastasis (P=0.058). hTe patients with high Cat X levels experienced sig-niifcantly shorter overall survival rates compared with those with low Cat X. Univariate analysis indicated that Cat X and TNM stage were related to overall survival. Multivariate Cox analysis indicated that TNM stage may be used as an independent prog-nostic variable in patients with lung cancer. Conclusion Cat X and cystatin C levels were signiifcantly higher in patients with lung cancer. Cat X and cystatin C detection in the sera may contribute to the diagnosis of lung cancer and may be used to evalu-ate the prognosis of patients with NSCLC.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

OBJECTIVE: To compare the effects of robotic and laparoscopic-assisted radical total gastrectomy on lymph node dissection and short-term outcomes in patients with Siewert type II adenocarcinoma of esophagogastric junction (AEG). METHODS: Inclusion criteria: the tumor center was located between 2 cm above and below the esophagogastric junction and was confirmed as adenocarcinoma by endoscopic biopsy. EXCLUSION CRITERIA: tumor with local invasion of the liver,spleen, pancreas or other organs; intraoperative finding of tumor dissemination or distant metastasis; patients undergoing palliative surgical treatment or preoperative neoadjuvant chemotherapy; patients with serious heart diseases, lung diseases, liver diseases, kidney diseases and other comorbidities; patients with multiple primary cancers;patients receiving emergency surgery. According to the above criteria, 82 patients with Siewert type II AEG who underwent gastrointestinal surgery at the Affiliated Hospital of Qingdao University from October 2014 to October 2018 were enrolled in the study. They were randomly divided into robotic surgery groups (41 cases) and laparoscopic group (41 cases) according to a computer-generated randomized allocation table. Both groups underwent radical total gastrectomy plus D2 lymph node dissection through the transabdominal esophageal hiatus approach. The intraoperative conditions and postoperative short-term outcomes were compared between two groups, including surgery time, intraoperative blood loss, length of esophagectomy, postoperative complications, postoperative gastrointestinal recovery time, length of hospital stay, postoperative unplanned reoperation rate and rehospitalization rate. Mean±SD is used for the measurement data that conforms to the normal distribution, and two independent sample t-tests are used to compare the two groups; the comparison of the count data is performed by the χ² test. RESULTS: There were 35 males (85.4%) with age of (62.3±10.0) years and body mass index of (24.4±3.2) kg/m² in the robotic surgery group. There were 37 males (90.2%) with age of (62.5±10.0) years and body mass index of (23.8±2.6) kg/m² in the laparoscopic group. No significant differences in the baseline data between two groups were found (all P>0.05). All the patients of both groups completed R0 resection successfully without conversion to laparotomy or perioperative death. Compared with the laparoscopic group, the robotic group had less intraoperative blood loss [(70.7±39.9) ml vs. (110.2±70.6) ml, t=3.118, P=0.003], longer resected esophagus [(3.0±0.7) cm vs. (1.9±0.5) cm, t=8.759, P<0.001], but longer setup time [(56.5±7.4) minutes vs. (36.0±6.6) minutes, t=4.241, P<0.001], and higher hospitalization costs [(122 317.31±57 789.33) yuan vs. (99 401.56±39 349.53) yuan, t=2.099, P=0.039], whose differences were statistically significant (all P<0.05). The total number of harvested lymph node in the robotic surgery group was 39.2±15.3,which was significantly higher than that in the laparoscopic group (33.0±12.1) (t=0.733, P=0.047). In the robotic group and the laparoscopic group, the mediastinal lymph node No.110 and No.111 were 3.6±1.2 vs. 1.5±1.0 and 3.7±2.0 vs. 1.8±1.1, respectively, with significant difference (t=10.138, P<0.001, t=8.227, P<0.001); axillary lymph node No.19 and No.20 were 2.3±1.2 vs. 1.1±0.9 and 2.0±1.0 vs. 1.0±0.1, respectively, with significant difference (t=7.082, P<0.001,t=8.672,P<0.001). There were no significant differences in the total number of abdominal lymph node and the number of lymph node in abdominal stations between two group (all P>0.05). The highest lymph node metastasis rate was approximately 20% and observed in No.1, No.2, No.3, and No.7, followed by No.8a, No.9, No.11p, and No.110 with around 5%. The lymph node metastasis rate in other stations (No.4sa, No.4sb, No.4d, No.5, No.6, No.11d, No.12a, No.19, No.20 and No.111) was less than 5%.There were no significant differences in postoperative complication rate, postoperative fever time, postoperative exhaust and defecation time, fluid diet time, and postoperative hospital stay (all P>0.05). There were 2 patients(4.9%) with unplanned reoperation and 1 patient (2.4%) with unplanned re-admission in the laparoscopic group,while 3 patients (7.3%)with unplanned reoperation and 2 patients (4.9%)with unplanned re-admission in the robotic surgery group, whose differences were also not statistically significant (χ²=0.240,P=0.675;χ²=0.346,P=1.000). CONCLUSION Robot-assisted radical total gastrectomy for Siewert II AEG is safe and feasible, which is characterized by more sophisticated operation, less blood loss and higher quality of lymph node dissection, especially for subphrenic and inferior mediastinal lymph nodes.
Adenocarcinoma ; classification ; pathology ; surgery ; Aged ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; Esophagogastric Junction ; pathology ; surgery ; Female ; Gastrectomy ; Humans ; Laparoscopy ; Lymph Node Excision ; methods ; Male ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures ; Stomach Neoplasms ; classification ; pathology ; surgery ; Treatment Outcome