ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P＜0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.01),and promoted the expression of p-SHP-2 protein(P＜0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P＜0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P＜0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P＜0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P＜0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.

Objective:To investigate the overall recurrence rate and the pattern of treatment failure in thoracic esophageal cancer (TEC) patients after minimally invasive esophagectomy (MIE), and to evaluate the significance of adjuvant therapy after MIE.Methods:Clinical data of TEC patients who underwent MIE with or without neoadjuvant chemotherapy in the Fourth Hospital of Hebei Medical University between 2016 and 2018 were retrospectively analyzed. The pathology-based lymph node metastasis (LNM) rate, overall recurrence rate, and pattern of treatment failure following MIE were analyzed by SPSS 26.0 statistical software. Cox regression model was used to identify the high-risk factors for recurrent disease. Propensity score matching was performed to compare the survival of patients between the postoperative radiotherapy group and non-radiotherapy group.Results:A total of 443 eligible patients were enrolled in this study, and the pathology-based LNM rate in all groups was 42.0%. The overall recurrence rate was 34.8%. Regional lymphatic metastasis was the most frequent pattern of recurrence (24.2%), followed by distant metastasis (19.4%). Multivariate Cox regression analysis identified pT 3-4 stage and pN + stage as the independent risk factors for recurrence. At the same time, the total number of lymph nodes dissected ≥12 and the number of lymph nodes dissected ≥7 in the neck clavicle and upper mediastinum could reduce the risk of tumor recurrence. The 1-, 3-, and 5-year disease-free survival (DFS) rates in the postoperative radiotherapy group and non-radiotherapy group were 83.5%, 66.8%, 60.7%, and 79.2%, 61.6%, 57.2%, respectively ( χ2=0.13, P=0.715). The 1-, 3-, and 5-year overall survival (OS) rates in two groups were 92.0%, 72.0%, 67.5% and 84.0%, 68.0%, 55.4% , respectively ( χ2=0.43, P=0.513). Conclusions:Regional lymphatic and distant metastases are the main patterns of recurrence for TEC patients after MIE with or without neoadjuvant chemotherapy. pT 3-4 stage, pN + stage, insufficient total number of lymph node dissection and insufficient number of lymph nodes in neck supraclavicular and upper mediastinal dissection are high-risk factors for postoperative recurrence. The survival rate in the postoperative radiotherapy group tends to be higher than that in the non-radiotherapy group. Adjuvant therapy, including postoperative radiotherapy, may remain necessary.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To study the relationship between pancreaticobiliary maljunction (PBM) with cholangiopancreatic diseases, and to evaluate the efficacy and safety using endoscopic therapy for PBM.Methods:The clinical data of 734 patients treated with ERCP at the Affiliated Hospital of Guizhou Medical University from May 2016 to April 2020 were analyzed retrospectively. Of 31 PBM patients who were finally included in this study, there were 23 patients with benign diseases and 8 patients with malignant diseases. Using the diameter of bile duct, these patients were divided into two groups: dilated bile duct group and the non-dilated bile duct group. The general characteristics of patients, incidences of cholangiopancreatic disease, endoscopic treatment, therapeutic efficacy and follow-up data were analyzed.Results:Of the 31 patients with PBM, 11 were males and 20 were females, aged (56.7±16.2) years. There were 4 patients with choledochal cyst (12.9%) and 6 patients with biliary cancer (19.4%). The incidences were significantly higher than those in non-PBM patients (0.9% and 5.3%, respectively, P<0.05). All 31 patients with PBM underwent endoscopic EST treatment, including 15 patients (48.4%) treated with endoscopic naso-biliary drainage (ENBD), 9 patients (29.0%) with endoscopic retrograde biliary drainage (ERBD), 4 patients (12.9%) with endoscopic papillary balloon dilatation (EPBD)+ ENBD, 1 patient (3.2%) with endoscopic metal biliary endoprothesis (EMBE)+ ENBD, 1 patient with ERBD+ endoscopic retrograde pancreatic drainage (3.2%), and 1 patient with EPBD+ ERBD+ EMBE (3.2%). The operative success rate was 100%. Serum AST, ALT, ALP, GGT, TBil and DBil levels of patients in the benign group and malignant group were significantly decreased postoperatively when compared with the preoperative levels (all P<0.05). One patient (3.2%) developed post ERCP pancreatitis. The preoperative and postoperative NRS scores of the patients in the benign group were 7(6, 8) points compared to 0 (0, 1) points, respectively ( P<0.05). All the 23 patients in the benign group were followed up for (25.13±12.90) months. There were no patients who were loss to follow-up. There was no malignant transformation. Three PMB patients with dilated bile ducts still had attacks of abdominal pain or jaundice. The symptoms of the remaining 20 patients were completely relieved, giving a treatment efficacious rate of 87.0% (20/23). Conclusions:PBM was closely related to choledochal cysts, biliary cancer and other diseases. Endoscopic treatment was efficacious and safe, and provided a safe and feasible treatment in preventing future cholangiopancreatic attacks.

Objective:To study the effectiveness and safety of perioperative lactated Ringer solution (LRS) in prevention and alleviation of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) under different fluid replacement regimens to arrive at the most precise quantitative fluid replacement regimen.Methods:Pubmed, Embase, Cochrane Library Database, Wanfang Database, CNKI, and VIP were searched from inception to February 2020. Randomized controlled trials on LRS in prevention and alleviation of PEP under different fluid replacement regimens were collected. The experiment group was actively rehydrated with LRS during the perioperative period, and the amount of rehydration was significantly higher than that of the control group. The control group was given standard dose of LRS or normal saline. Two researchers independently selected the articles based on predetermined inclusion and exclusion criteria, extracted the data, and evaluated the risk of bias. RevMan 5.3 software was used for statistical analysis.Results:Ten studies with 2 261 patients were included, with 1 140 patients in the experiment group, and 1 121 patients in the control group. Meta-analysis showed that when the experiment group was given LRS at a rate of 5.0 ml·kg -1·h -1 during the perioperative period for about 9 hours and compared with the control group, the incidence of PEP in the experiment group was significantly reduced ( OR=0.32, 95% CI: 0.21-0.48, P<0.05). The incidence of moderate to severe PEP was also significantly reduced ( OR=0.28, 95% CI: 0.09-0.84, P<0.05). There was no increase in the incidence of adverse reactions related to fluid replacement. However, there were no significant differences in the incidence of PEP, and in moderate to severe PEP between the two groups when LRS was given at a rate of 4.0~4.5 ml·kg -1·h -1 within 9 hours, and less than 4.0 ml·kg -1·h -1 within 24 hours of total rehydration time (all P>0.05). Conclusion:During the perioperative period, the current evidence showed that it is most reasonable to give the fluid replacement regimen with aggressive hydration using LRS at a rate of 5.0 ml·kg -1·h -1 in about 9 hours to prevent and alleviate PEP. This is recommended for clinical practice and is worthy of further future studies.

ObjectiveTo systematically review the efficacy and safety of endoscopic papillary large balloon dilation (EPLBD) versus endoscopic sphincterotomy combined with large balloon dilation (ESBD) in the treatment of large common bile duct stones (≥10 mm). MethodsPubmed, Embase, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for related articles published up to March 2020. Two reviewers independently performed article screening, data extraction, and quality assessment, and RevMan 5.3 software was used for statistical analysis. ResultsA total of 11 studies (6 randomized controlled trials and 5 non-randomized controlled trials) were included, with 1282 patients in total. The meta-analysis showed that in the 6 randomized controlled trials, there were no significant differences between the EPLBD group and the ESBD group in initial stone clearance rate (odds ratio ［OR］=0.71, 95% confidence interval ［CI］: 0.45-1.12, P=0.14), overall stone clearance rate (OR=1.39, 95%CI: 0.65-2.96, P=0.39), rate of use of mechanical lithotripsy (OR=1.19, 95%CI: 0.75-1.89, P=0.46), and incidence rate of early complications (OR=1.10, 95%CI: 0.60-2.03, P=075); in the 5 non-randomized controlled trials, there were no significant differences between the EPLBD group and the ESBD group in initial stone clearance rate (OR=0.64, 95%CI: 0.35-1.15, P=0.13), overall stone clearance rate (OR=0.46, 95%CI: 0.19-112, P=009), and incidence rate of early complications (OR=1.20, 95%CI: 0.65-2.21, P=0.56), but the EPLBD group had a significantly higher rate of use of mechanical lithotripsy than the ESBD group (OR=1.96, 95%CI: 1.26-3.05, P=0.003). ConclusionEPLBD and ESBD have similar efficacy and safety in the treatment of large common bile duct stones, while EPLBD may increase the risk of the use of mechanical lithotripsy. More high-quality randomized controlled trials are needed to confirm this conclusion.

Objective: To examine the impact of metabolic syndrome (MS) on the clinicopathological characteristics and prognosis of patients with colorectal cancer (CRC). Methods: The clinical data of 650 patients with CRC admitted in Shanxi Provincial Cancer Hospital between January 2010 and December 2011 were retrospectively analyzed. Among 650 patients there were 190 cases complicated with MS (MS group) and 460 cases without MS (non-MS group), the clinicopathological features and prognosis were compared between two groups. Results: The serum insulin and insulin-like growth factor-1 (IGF-1) levels in MS group were significantly higher than those in non-MS group [(9.2±4.7) vs.(6.8±4.7)μIU/L, t=8.88, P<0.01 and (200.2±44.1) vs.(136.7±63.2)mg/L,t=12.63, P<0.01]. The proportions of stage T₃ and T₄ cancer, extra-regional lymph node metastasis (ELN), and TNM stage Ⅲ and Ⅳ patients in MS group were significantly higher than those in non-MS group [(83.2% (158/190) vs. 72.6% (334/460), χ²=8.19, P=0.04; 9.5% (18/190) vs. 4.8%(22/460),χ²=8.61, P=0.04; 56.3% (107/190) vs. 45.2%(208/460), χ²=8.22, P=0.04, respectively]. The 5-year disease-free survival (DFS) in MS group was significantly lower than that in non-MS group [57.9%(99/171)vs. 66.1%(279/422), P<0.01]. Multivariate analysis indicated that MS(HR=1.623, 95%CI:1.511-1.963, P=0.03), IGF(HR=1.382, 95%CI:1.031-1.765, P=0.02) and, ELN(HR=4.270, 95%CI:2.177-7.463, P<0.01)were independent factors affecting the prognosis of CRC patients. Conclusion Metabolic syndrome is one of the risk factors affecting the prognosis of CRC patients.

Objective To investigate the expression of insulin-like growth factor 1 (IGF-1), insulin growth factor receptor 1(IGF-1R)and insulin growth factor receptor 2(IGF-2R)in colorectal cancer, and their relationship with the relevant clinicopathological factors. Methods Immunohistochemical SP method was used to detect the expression of IGF-1,IGF-1R and IGF-2R in 154 cases of colorectal cancer tissues,58 cases of benign disease tissues (colorectal adenoma, polyps) and 90 normal tissues. Results The positive rate of IGF-1 and IGF-1R expression in colorectal cancer tissues [93.5%(144/154), 70.1%(108/154)] was higher than that in benign diseases [51.7%(30/58), 51.7%(30/58)] and adjacent normal tissues [18.9%(17/90), 35.6%(32/90)] (P=0.001). The positive expression rate of IGF-1 and IGF-1R in colorectal cancer tissue, benign disease tissue and adjacent normal tissues decreased gradually, and there was significant difference between any two groups (P<0.05). The positive expression rate of IGF-2R had no significant difference between any two groups (P>0.05). IGF-2R was significantly different between any two groups (P<0.05). The expression of IGF-1R and IGF-2R in colorectal cancer tissues were not significantly correlated with gender, location, tumor size, family history, depth of tumor invasion and local lymph node metastasis (all P>0.05).IGF-1 was positively correlated with the body mass index(r=0.169,P=0.036).IGF-2R was negatively correlated with age (r=-0.196, P=0.015), and positively correlated with TNM staging in patients with colorectal cancer (r=0.227, P=0.005). The expression of IGF-1 was positively correlated with IGF-1R (r=0.281, P=0.000 1). There was no significant correlation between IGF-1 and IGF-2R in cancer tissues (P>0.05). Conclusion IGF-1 and IGF-1R may promote the occurrence of colorectal cancer, and IGF-2R may be associated with the progress of colorectal cancer,and obesity is a risk factor for incidence of colorectal cancer.

Objective:To explore the effects of combination of epirubicin (EPI) and anti-CD47 antibody on therapy of breast cancer.Calreticulin ( CRT) and CD47 on DC-mediated phagocytosis.Methods: Breast cancer cells MCF-7 and MDA-MB-231 were treated with EPI , and expression of calreticulin ( CRT ) and CD47 on cell surface were detected by flow cytometry or immunofluorescence.DC were isolated from human peripheral blood , and cocultured with epirubicin-treated breast cancer cells in the present of anti-CD47 or anti-CRT antibody ,and the phagocytosis of DC was assessed.Results:Untreated breast cancer cells MCF-7 and MDA-MB-231 did not express CRT on the surface of cells ,but high level of CD47 was detected.After EPI treatment,CRT exposed on the cells surface,and the expression of CD47 was reduced.The results showed that EPI or anti-47 antibody alone increased DC-mediated phagocytosis ,and combination treatment marked enhanced this effects.Further more, in addition of anti-CRT antibody reduced the phagocytosis of DC.Conclusion:EPI could induce CRT exposure on the tumor cell surface ,and enhanced DC-mediated phagocytosis when combination with anti-CD47 antibody.The phagocytosis of DC on tumor cells were modulated by both ecto-CRT and CD47.This study provide a new effective strategy for the use of anti-CD47 antibody among the chemotherapy of breast cancer.