Objective To evaluate the condition of oxidative stress and immunosuppression in early stage of severe sepsis,and investigate the correlation between them. Methods A prospective random control study in-cluded patients group(n=51)and control group(n=31). The concentration of serum superoxide dismutase was measured by enzyme linked immunosorbent assay(ELISA),CD4+CD25+Treg% was measured by flow cytometry , respectively. The difference between two groups was compared and the correlation between parameters in patients group was evaluated. Results The concentration of serum SOD was lower than control group (P < 0.01). CD4+CD25+Treg% significantly high,compared to the control group(P < 0.01). There was no strong correlation be-tween parameters in patients group. Conclusion Oxidative stress and immunosuppression are exist in the early stage of severe sepsis.

Objective To study the expression of interleukin-6 (IL-6) and hepcidin in patients with diffuse large B-cell lymphoma (DLBCL) and their significance in anemia. Methods 45 DLBCL patients with or without anemia were analyzed. Peripheral blood samples were collected during diagnosis, and the concentrations of IL-6, hepcidin, serum ferritin and hemoglobin (Hb) were measured. 24 healthy volunteers were collected as controls. Results The levels of plasma hepcidin and IL-6 in patients with DLBCL were (347±171)μg/L and 0.27 ng/L (0-9.61 ng/L), respectively, and compared with those [(175 ± 92)μg/L] and 0 ng/L in healthy controls, the differences were statistically significant (both P<0.001). Plasma hepcidin levels in patients with high lactate dehydrogenase (LDH) (P=0.003), B symptoms (P=0.040) or age-adjusted international prognostic index (IPI)>1 (P=0.010) were increased. The levels of IL-6 in patients of male (P=0.003), stage Ⅲ-Ⅳ (P=0.008) or IPI>1 (P=0.004) were significantly higher. The level of hepcidin was highly correlated with serum ferritin (r=0.77, P<0.001), weakly correlated with IL-6 (r=0.31, P=0.030), and not correlated with Hb (r=-0.12, P=0.3). There was a negative correlation between IL-6 expression and Hb (r=-0.35, P=0.009). Multivariate analysis showed that IL-6 could predict anemia (P=0.03), whereas hepcidin could not (P=0.89). Conclusion The elevated hepcidin level is frequent in DLBCL, and the elevated IL-6 plays the major role in the development of anemia.

Objective:To investigate the risk factors of low anterior resection syndrome (LARS)after low anterior resection of rectal cancer (Dixon).Methods:This retrospective study was conducted in Peking University First Hospital and Traditional Chinese Medicine Hospital of Shanxi Provice from Jan 2012 to Jun 2019. A cohort of 504 patients with rectal cancer was enrolled in the study. All the patients underwent anterior resection. The relationship between clinical-pathological data were analyzed retrospectively. Univariate analysis using χ 2 test. Logistic regression analysis was used to screen the influencing factors of LARS, and the Nomogram method was used to score each factors. Results:Univariate analysis showed that BMI≥28 kg/m 2(χ 2=9.450, P=0.002), the distance from the lower edge of the tumors to the anus <6 cm (χ 2=12.070, P=0.001), high ligation of the inferior mesenteric artery (IMA) (χ 2=8.279, P=0.004), preoperative neoadjuvant therapy (χ 2=11.230, P=0.001), postoperative anastomotic leakage (χ 2=11.840, P=0.001) were associated with severe LARS.Multivariate analysis showed that the distance from the lower edge of the tumors to the anus <6 cm ( OR=1.861, 95% CI: 1.289-2.688, P=0.001), BMI≥28 kg/m 2 ( OR=1.747, 95% CI: 1.022-2.987, P=0.041), high IMA ligation ( OR=1.688, 95% CI: 1.157-2.463, P=0.007), preoperative neoadjuvant therapy ( OR=2.719, 95% CI: 1.343-5.505, P=0.005) were independent risk factors for LARS. Nomogram model showed that the total factor ranged from 2 to 212, and the corresponding risk rate ranged from 30% to 80%. The patients with higher score have greater risk for severe LARS. The area under the predictive power curve of Nomogram model (AUC) was 0.749 (95% CI: 0.705-0.793, P<0.001). Conclusion:Lower tumor location, obesity, preoperative neoadjuvant therapy, high IMA ligation and postoperative anastomotic leakage increase the risk of severe LARS.

Objective:To explore the putative role of CD40 and COX-2 expression in human esophageal squamous cell carcinoma(ESCC)and to analyze their possible relationship with angiogenesis in ESCC.Methods:The expression of CD40 and COX-2 was detected in 79 ESCC and 28 normal esophageal epithelial tissue samples with immunohistochemical staining.The microvessel density by CD34 was determined and the clinicopathological significance of CD40 and COX-2 expression in ESCC was analyzed.In addition,the expression of CD40 and COX-2 in esophageal squamous cell carcinoma cell line Eca109 and primary cultured normal esophageal epithelial cells in vivo was comparatively studied with immunocytochemical staining andWestern blot.Results:Compared with that in normal epithelial tissues,the expression of CD40 and COX-2 in ESCC was significantly higher(54.43%vs 10.71%:69.62%vs 17.86%:respectively,P<0.05).The positive expression rate of CD40 in ESCC cases with lymph node metastasis was significantly higher than that in those without lymph node metastasis(70.37%vs 46.1 5%.P<0.05).No correlation was found between CD40 expression and patient age,sex,tumor location,size and differentiation of tumors.No clinicopathological significanca of COX-2 expression in ESCC was found.There was a positive correlation between CD40 expression and COX-2 expression in esophageal squamous cell carcinoma(P<0.05,φ=0.446).The mean MVD value in ESCC was significantly higher than that in normal esophageal tissue(25.02±5.52 vs 12.09±4.55,P<0.05).MVD value in ESCC was closely correlated with lymph node metastasis.The mean MVD value in ESCC cases with positive CD40 and COX-2 expression was higher than that in those with negative CD40 and COX-2expression(26.37±6.02 vs 22.58±5.25.P<0.05).Western blot results showed that CD40 and COX-2 expression in Eca109 was higher than that in cultured normal esophageal epithelial cells (P<0.05).Conclusion:The expression of CD40 is involved in the carcinogenesis and progression of esophageal squamous cell carcinoma.CD40 may play an important role in the angiogenesis of ESCC through promoting COX-2 expression.

Objective:To investigate the clinical value of fascia orientated laparoscopic lateral lymph node dissection (LLND) in radical excision for advanced low rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 100 patients with advanced low rectal cancer who were admitted to Peking University First Hospital from January 2013 to August 2021 were collected. There were 69 males and 31 females, aged 58(range, 32?85)years. Patients underwent laparoscopic total mesorectal excision and fascia oriented LLND. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) results of histopathological exa-mination; (4) follow-up. Follow-up was conducted by telephone interview, outpatient examination and medical records review to detect survival, disease progression, tumor recurrence and metastasis of patients up to August 2021. Survival time was from the surgery date to death or the last follow-up time of patients. Measurement data were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Results:(1) Surgical situations. Of the 100 patients, 44 cases underwent neoadjuvant therapy and 56 cases didn′t receive preoperative therapy. Of the 100 patients with laparoscopic radical excision for advanced low rectal cancer, 60 cases underwent low anterior resection of rectal cancer including 49 cases with unilateral LLND and 11 cases with bilateral LLND,20 cases underwent abdomin-operineal resection for rectal cancer including 16 cases with unilateral LLND and 4 cases with bilateral LLND, 12 cases underwent total pelvic exenteration including 6 cases with unilateral LLND and 6 cases with bilateral LLND, 5 cases underwent Hartmann surgery including 3 cases with unilateral LLND and 2 cases with bilateral LLND, 3 cases underwent posterior pelvic exenteration including 2 cases with unilateral LLND and 1 case with bilateral LLND. The operation time and volume of intraoperative blood loss were 258(range,200?325)minutes and 100(range, 50?200)mL. There were 19 patients with low anterior resection of rectal cancer and protective ileostomy simultaneously. Three patients encountered intraoperative lymph node invasion of the obturator nerve, causing injury of the nerve at dissection. Of the 100 patients, 12 cases with total pelvic exenteration were dissected the ureterohypogastric nerve fascia and 88 cases were preserved the complete ureterohypogastric nerve fascia. (2) Postoperative situations. There was no perioperative death in the 100 patients. The time to postoperative catheter removal and duration of hospital stay of the 100 patients were 4(range, 3?7)days and 11(range, 9?15)days, respectively. There were 26 cases with postoperative complications. (3) Results of histopathological examination. The maximum tumor diameter was 4.5(range, 3.8?5.9)cm. There were 21 patients with mass type of tumor pross and 79 cases with ulcerative type. There were 82 cases with high and moderate differentiation of tumor differentiation degree, 18 cases with low differentiation and undifferentiated adenocarcinoma (signet ring cell carcinoma). There were 14 cases in TNM stage Ⅰ, 38 cases in TNM stage Ⅱ, 48 cases in TNM stage Ⅲ. There were 16 cases in stage T0?2 and 84 cases in stage T3?4. There were 52 cases in stage N0 and 48 cases in stage N1?2. The total number of lymph node dissected was 23(range, 18?27)per person and the total number of unilateral LLND was 5(range, 3?9)per person. There were 36 of 100 patients with positive lateral lymph nodes, including 14 cases with neoadjuvant therapy. (4) Follow-up. Of the 100 patients, 97 cases were followed up for 21(range, 1?69)months. The 2-year overall survival rate was 81.6% and 2-year disease progression free survival rate was 70.6%. During the follow-up, 4 of 97 patients had presacral tumor recurrence and 1 case had tumor recurrence in the LLND region. There were 11 cases with liver metastasis, 5 cases with bone metastasis, 2 cases with the contralateral lymph node metastasis of unilateral LLND, 2 cases with paraaortic lymph node metastasis, 2 cases with transcoelomic spread. Of the 97 patients who were followed up, 76 cases survived with free disease, 4 cases survived with tumor, 15 cases died of tumor and 2 cases died of other diseases.Conclusion:The fascia orientated laparoscopic LLND is safe and feasible in radical excision for advanced low rectal cancer.

Objective:To investigate whether 6-shogaol (6-SH) alleviates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal autophagy and calcium overload by promoting the expression of microRNA-26a-5p (miR-26a-5p) and inhibiting death-associated protein kinase 1 (DAPK1), and to explore its potential mechanisms.Methods:Primary cultured logarithmic growth phase mouse hippocampal neurons HT22 cells were taken and cell counting kit-8 (CCK-8) was used to detect cell viability, searching for the optimal concentration of Na 2S 2O 4. HT22 cells were divided into blank control group (NC group), OGD/R group (sugar-free culture medium + 10 mmol/L Na 2S 2O 4 treatment for 1.5 hours followed by normal culture medium for 4 hours), 6-SH intervention group (cultured with 10 μmol/L 6-SH for 4 hours after OGD), negative control inhibitor pretreatment group (transfected with negative control inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours), and miR-26a-5p inhibitor pretreatment group (transfected with miR-26a-5p inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours). Cell viability of each group was detected by CCK-8 method; cell ultrastructure was observed under transmission electron microscopy; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of DAPK1 and miR-26a-5p; molecular docking were used to verify the interaction between 6-SH and miR-26a-5p; dual-luciferase assay was used to verify the targeting relationship between DAPK1 and miR-26a-5p; flow cytometry was used to determine the levels of intracellular Ca 2+; Western blotting was used to detect the protein expressions of phosphorylated-glutamate receptor 2B (p-NMDAR2B) Ser1303, DAPK1, autophagy related protein Beclin1, light chain 3 (LC3), and p-DAPK1 Ser308; immunofluorescence was used to detect the expression of LC3 and Beclin1. Results:The results of the CCK-8 assay showed that the cell viability of the 6-SH intervention group was significantly increased compared to the OGD/R group, while the cell viability of the miR-26a-5p inhibitor pretreatment group was significantly decreased compared to the 6-SH intervention group. Transmission electron microscopy revealed that the number of autophagosomes in the 6-SH intervention group was significantly reduced compared to the OGD/R group, while the number of autophagosomes in the miR-26a-5p inhibitor pretreatment group was significantly increased compared to the 6-SH intervention group. RT-qPCR results showed that compared with the OGD/R group, the expression of miR-26a-5p was significantly upregulated and the expression of DAPK1 mRNA was significantly downregulated in the 6-SH intervention group; compared with the 6-SH intervention group, the expression of miR-26a-5p was significantly downregulated and the expression of DAPK1 mRNA was significantly upregulated in the miR-26a-5p inhibitor pretreatment group. Molecular docking verified the interaction between 6-SH and miR-26a-5p. Dual-luciferase reporter gene assay showed that compared with the negative control group, mmu-miR-26a-5p significantly downregulated the luciferase expression of m-DAPK1-3UTR-WT, indicating a binding interaction between them. Flow cytometry results showed that compared with the OGD/R group, the level of intracellular Ca 2+ was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the level of Ca 2+ was significantly increased in the miR-26a-5p inhibitor pretreatment group. Western blotting results showed that compared with the OGD/R group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly decreased in the 6-SH intervention group (p-NMDAR2B Ser1303/β-actin: 2.34±0.27 vs. 4.78±0.39, DAPK1/β-actin: 1.40±0.13 vs. 2.37±0.21, Beclin1/β-actin: 2.61±0.32 vs. 4.32±0.29, LC3/β-actin: 2.52±0.45 vs. 5.09±0.18, all P < 0.05), while the protein expression of p-DAPK1 Ser308 was significantly increased (p-DAPK1 Ser308/β-actin: 0.66±0.09 vs. 0.40±0.02, P < 0.05); compared with the 6-SH intervention group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly increased in the miR-26a-5p inhibitor pretreatment group (p-NMDAR2B Ser1303/β-actin: 4.08±0.14 vs. 2.34±0.27, DAPK1/β-actin: 1.96±0.15 vs. 1.40±0.13, Beclin1/β-actin: 3.92±0.31 vs. 2.61±0.32, LC3/β-actin: 4.33±0.33 vs. 2.52±0.45, all P < 0.05), while the expression of p-DAPK1 Ser308 protein was significantly decreased (p-DAPK1 Ser308/β-actin: 0.33±0.12 vs. 0.66±0.09, P < 0.05); immunofluorescence staining showed that compared with the OGD/R group, the fluorescence intensity of LC3 and Beclin1 was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the fluorescence intensity of LC3 and Beclin1 was significantly increased in the miR-26a-5p inhibitor pretreatment group. Conclusion:6-SH can alleviate neuronal damage by regulating miR-26a-5p/DAPK1 to reduce autophagy and calcium overload in cells.

Objective:To evaluate CT and or MRI imaging in the diagnosis of lateral lymph node metastasis in patients of middle and low rectal cancer.Methods:In this study, 112 lateral lymph nodes were harvested in 79 patients with middle and low rectal cancer. The relationship between the preoperative imaging features of the lateral lymph nodes and the postoperative pathology was evaluated.Result:Thirty-eight cases (48%) were pathologically confirmed to have lateral lymph node metastasis. The diameter of metastasis-positive lateral lymph nodes was significantly larger than that of metastasis-negative lateral lymph nodes ( P<0.01). Multivariate analysis of clinical features and imaging features found that, tumors poorly differentiated, mucinous adenocarcinoma, signet ring cell carcinoma ( P=0.006), and the largest short diameter of the lateral lymph node ≥7 mm ( P=0.024), uneven density or signal ( P=0.022) were independent risk factors for lateral lymph node metastasis. Conclusion:Poor tumor differentiation, lateral lymph node maximum short diameter ≥7 mm, density or signal unevenness are independent risk factors for lateral lymph node metastasis in middle and low rectal carcinoma.

Objective This study aimed to assess the clinical efficacy of Shenling Baizhu Granules in treating low anterior resection syndrome(LARS)in rectal cancer.Methods The study employed a randomized,double-blind,placebo-parallel controlled,single-center,validity-tested clinical trial design.December 2019 to June 2022,the Department of Gastrointestinal Surgery and Integrated Traditional Chinese and Western Medicine of Peking University First Hospital recruited 110 patients who had undergone low anterior resection(LAR)for rectal cancer and subsequently developed LARS.These patients,meeting the enrollment criteria,were randomly assigned into the treatment group(55)and the control group(55)using the double-blind method principle.The randomization table was generated by SAS 9.2 software employing the double-blind method.The treatment group received oral Shenling Baizhu Granules,while the control group received oral placebo granules.Both groups commenced treatment on the 10th day after-surgery for 30 consecutive days.Patients were evaluated using LARS score,traditional Chinese medicine(TCM)symptom grading,and XU Zhongfa score before treatment,on the 15th day of treatment,and on the 1st day after treatment cessation.Results Out of 110 patients,107 were included in the full analysis set for efficacy analysis:55 patients in the treatment group and 55 patients in the control group.One case in the treatment group was excluded(against protocol),and two cases in the control group were excluded(one lost to follow-up,one against protocol).Baseline data between the two groups were consistent,with no statistically significant difference.Before treatment,LARS scores for the treatment and control groups were 33.0(31.0,36.0)and 34.0(32.0,37.0)respectively.Patients with TCM symptom scores of grades 2 to 3 accounted for 92.73％and 90.57％in the treatment and control groups,respectively,with no statistically significant difference.After 30 days of treatment,LARS scores for the treatment and control groups were 21.0(19.8,23.0)and 26.0(22.0,28.0)respectively.The percentage of patients with TCM symptom scores of grades 2 to 3 decreased to 33.33％in the treatment group and 66.04％in the control group,with a statistically significant difference.Shenling Baizhu Granules showed rapid improvement in watery or loose stools in post-operative rectal cancer patients.After 30 days of treatment,Shenling Baizhu Granules significantly improved appetite,stool consistency,abdominal distension,abdominal pain,and eructation symptoms in postoperative rectal cancer patients.Before treatment,the XU Zhongfa scores for the treatment and control groups were 3.0(2.0,4.3)and 4.0(2.0,4.0)respectively,with no statistically significant difference.After 30 days of treatment,the XU Zhongfa scores for the treatment and control groups were 7.0(6.0,8.0)and 6.0(5.0,7.0)respectively,with the treatment group significantly higher than the control group(P＜0.01).Conclusion Shenling Baizhu Granules can effectively improve LARS symptoms in patients following LAR of rectal cancer within a short period of time.

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

Objective:To analyze and screen the key genes of sepsis secondary to pulmonary infection by bioinformatics, and to provide theoretical basis for the basic research of the disease and find an ideal animal model program.Methods:Experiment 1 (bioinformatics analysis): gene expression data sets of pulmonary infection secondary sepsis patients and multiple sepsis animal models were screened by Gene Expression Omnibus (GEO) Database, and gene differences were analyzed by R software. Differential genes were analyzed by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Correlation analysis was conducted between differential genes and clinical symptoms in the data set of pulmonary infection secondary sepsis, and the correlation heat map between differential genes and clinical symptoms was drawn. Key genes were screened by weighted gene co-expression network analysis (WGCNA) and protein-protein interaction network analysis (PPIN) clustering. Experiment 2 (sepsis animal model preparation): male mice weighing 21-25 g were randomly divided into the key genes group and the control (Sham) group. And cecal ligation and puncture (CLP) was used to establish mouse sepsis model, while the mice in sham group were performed by exposure of cecum. And all the mice were scarified 24 hours after surgery to extract the total RNA from lung tissue, real time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression of key genes.Results:Experiment 1 (bioinformatics analysis): 319 differential genes were showed by GSE 134364 and GSE 65682 data set analysis of pulmonary infection secondary sepsis. And there was no genetic difference between community acquired pneumonia (CAP) and hospital acquired pneumonia (HAP) in patients with pulmonary infection secondary to sepsis. Obvious differences existed between differential genes in animal models, and there was no common differential gene. Differential genes in patients and animal models were similarly enriched in GO function, mainly in cell differentiation, regulation of cell process, and regulation of cellular response to stimuli, there were significant differences in pathway enrichment, among which, CLP animal models showed higher consistency with patients. The key genes obtained by WGCNA and PPIN analysis were MAPK14, NLRC4 and LCN2. Experiment 2 (sepsis animal model preparation): animal experiment results showed that the mRNA expressions of MAPK14, NLRC4 and LCN2 in lung tissue of CLP model mice were significantly up-regulated compared with the sham group.Conclusions:MAPK14, NLRC4 and LCN2 are key genes involved in the regulation of biological processes of pulmonary sepsis secondary to infection, and are potential research directions of this disease. What's more, CLP animal model can better reflect the biological characteristics of patients with pulmonary infection secondary sepsis, and is one of the ideal animal model schemes for pulmonary infection secondary sepsis.