Objective:To discuss the associations of mismatch repair(MMR)in gastric cancer with preoperative inflammatory indicators and clinicopathological features in the gastric cancer patients,and to construct a gastric cancer MMR predictive model based on preoperative inflammatory indicators and clinicopathological features of the gastric cancer patients,and to provide new ideas for evaluation of MMR status in gastric cancer.Methods:The data of 254 gastric cancer patients who underwent surgical treatment from September 2020 to October 2023 were included.According to the expression of MMR protein,the patients were divided into MMR normal(proficiout MMR,pMMR)group and MMR deficient(dMMR)group.The preoperative inflammatory indicators and clinicopathological features data of the gastric cancer patients in two groups were collected.The associations between inflammatory indicators,clinicopathological features,and MMR in dMMR group and pMMR group were analyzed using Chi-square test.The independent predictive factors for dMMR were selected to construct the nomogram.Receiver operating characteristic(ROC)curve and calibration curve were used to evaluate the predictive efficacy,and decision curve was used to evaluate the practicality of the predication model.Results:A total of 254 gastric cancer patients were included in the study,with 221 patients(87％)in pMMR group and 33 patients(13％)in dMMR group.There were statistically significant differences(P＜0.05)in age,tumor location,tumor differentiation degree,maximum tumor diameter,platelet-to-lymphocyte ratio(PLR),alkaline phosphatase(AKP),alkaline phosphatase-to-albumin ratio(AAR),fibrinogen(FB)-to-lymphocyte(FLR),FB-to-albumin(AL)(FAR),D-dimer(D-D),and FB of the gastric cancer patients between dMMR group and pMMR group.Univariate and multivariate Logistic regression analysis revealed maximum tumor diameter[odd ratio(OR)=2.958,95％confidence interval(CI):1.196-7.314,P=0.019],tumor location(OR=4.013,95％CI:1.596-10.089,P=0.003),tumor differentiation(OR=3.006,95％CI:1.250-7.230,P=0.014),FAR(OR=2.793,95％CI:1.179-6.616,P=0.020),and carbohydrate antigen 199(CA199)(OR=0.279,95％CI:0.084-0.929,P-0.038)were the independent predictors of dMMR.The area under the ROC curve(AUC)value of the gastric cancer MMR prediction model constructed based on inflammatory indicators and clinical pathological characteristics was 0.800 with the sensitivity of 0.851 and the specificity of 0.606.The calibration curve of the nomogram was found to fit the ideal curve well,and in Hosmer-Lemeshow test P=0.412,the clinical decision curve showed a better net benefit.Conclusion:The preoperative inflammatory indicators and clinicopathological features are associated with MMR in gastric cancer;maximum tumor diameter,tumor location,tumor differentiation,CA199,and FAR are the independent predictors of dMMR.The prediction model based on the above predictors could predict the MMR status of the dMMR gastric cancer patients.

Objective To analyze the influence of drainage volume on prognosis of acute hydrocephalus(AHC)after aneurysmal subarachnoid hemorrhage(aSAH)by continuous lumbar drainage.Methods A retrospective trial was conducted on 82 AHC patients after aSAH admitted to the First Affiliated Hospital of Chongqing Medical University between January 2017 and January 2022.In 6 months after discharge,modified Rankin Scale(mRS)score was used to evaluate the prognostic outcomes.Univariate and multivariate logistic regression analyses were performed on demographic factors,severity of subarachnoid hemorrhage(SAH)at admission,medical history,cerebral vasospasm,and lumbar drainage data.Then a nomogram prediction model was constructed.Results Univariate analysis found that World Federation of Neurosurgical Societies(WFNS)score,Hunt-Hess grade,modified Fisher grade,time for continuous lumbar drainage,shunt dependence,cerebral vasospasm,and drainage volume were factors affecting the prognosis of the patients.Then logistic regression analysis revealed that high WFNS score(OR:3.25,95％CI:1.11～9.48),high modified Fisher grade(OR:3.66,95％CI:1.08～12.35),shunt dependence(OR:15.56,95％CI:1.22～198.57),and cerebral vasospasm(OR:22.24,95％CI:3.08～160.68)were independent predictors for mRS score,while volume of continuous lumbar drainage(OR:0.57,95％CI:0.40～0.82)was an independent protective factor.ROC curve analysis indicated a good predictive performance of the model(AUC=0.898,95％CI:0.935～0.861).Internal validation through Bootstrap method demonstrated excellent discriminatory ability of the model(C-index=0.950,95％CI:0.904～0.996;adjusted C-index:0.934).Conclusion Increased volume of lumbar drainage is an independent protective factor for poor prognosis following aSAH and can improve the prognosis of SAH patients.

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Objective:To measure the anatomical parameters of the simulated low tibial tunnel of posterior cruciate ligament (PCL) based on knee CT images so as to provide clinical reference for accurate location of the tunnel.Methods:The CT images of 201 healthy knee joints collected at Department of Orthopedics, The Second Hospital of Lanzhou University from June 2016 to September 2021 were used for simulation of the PCL low tibial tunnel. The anatomical parameters of the tibial tunnel were measured using the RadiAnt DICOM Viewer. The primary measures included the angle between tibial plateau and tibial tunnel (ATPT) and the perpendicular distances from the tibial tunnel entrance and exit point to the tibial plateau (L1 and L2). The secondary measures included the angle between tibial plateau and posterior slope (PSA), the angle between tibial anatomical axis and central line of tibial tunnel (ATAA), the angle between posterior tibial slope line and the central line of tibial tunnel (APST), the anterior and posterior diameter of tibial plateau (APD), the length of posterior tibial slope (LPTS), and the length of tibial tunnel (LTT). The measurement results were analyzed according to the body height (divided into 3 groups: a 1.00 to 1.60 m group, a 1.61 to 1.70 m group, and a ≥1.71 m group) and gender using the software IBM SPSS 26.Results:The primary measures: ATPT was 37.0°±4.5°, and L1 and L2 were respectively (57.8±7.4) mm and (34.5±3.3) mm. The secondary measures: PSA 128.1°±5.4°, ATAA 52.7°±4.1°, APST 89.1°±5.9°, APD was (32.9±2.6) mm, LPTS (20.5±2.4) mm, and LTT (40.9±5.7) mm. After grouping by gender, there was no significant difference in PSA between men and women ( P>0.05) while there were significant differences in the other indexes between men and women ( P<0.05). After grouping by body height, there was no significant difference in ATPT, PSA, APST or ATAA between the 3 groups (1.00 to 1.60 m group, 1.61 to 1.70 m group and ≥1.71 m group) ( P>0.05) while there were significant differences in L1, L2, APD, LPTS and LTT between the 3 groups ( P<0.05). Conclusions:Based on the knee CT images, the primary measures of PCL low tibial tunnel are as follows: the angle between tibial plateau and tibial tunnel is 37.0°±4.5°, and the perpendicular distances from the tibial tunnel entrance and exit point to the tibial plateau are (57.8±7.4) mm and (34.5±3.3) mm, respectively. Gender and body height are the important factors influencing the above measurement outcomes.

Objective:To explore the effects of orienting three-dimensional porous network (type A) and honeycomb briquette-shaped vertically penetrating three-dimensional porous network (type B) on the vascularization rate of artificial dermis.Methods:The experimental research method was used. The artificial dermis was composed of a double layer of silicone layer and scaffold layer. Based on the difference of scaffold layer, they were divided into type A and type B artificial dermis (type A dermis and type B dermis, for short) containing type A and type B structure, respectively. The type A and type B structures were prepared by gradient freeze-drying technique and physical pore-making technique, respectively. The micro-morphology of two kinds of dermis scaffold was observed by scanning electron microscopy. The porosity of two kinds of dermis scaffold was measured by the Pyrex method. According to the method of national medical industry standard, the hydroxyproline content in degradation liquids and their residues in two kind of dermis were determined after degradation at 4, 8, 13, and 24 h, reflecting the degradation rates of two kinds of dermis. According to the random number table, L929 cells were divided into type A dermis group, type B dermis group, negative control group, and positive control group. The positive control group was added with minimum essential medium (MEM) containing 5% dimethyl sulfoxide, The negative control group was added with high-density polyethylene extract, and the other two groups were added with the corresponding extract. At 24 hours after culture, the growth rate of L929 cells was detected by methyl thiazolyl tetrazolium, and the cytotoxicity was graded. L929 cells and human umbilical vein endothelial cells (HUVECs) were inoculated into pore plates with two kinds of dermis preinstalled. On 1, 4, 7, and 14 d after inoculating, the adhesion and growth of L929 cells on the surfaces of the two kinds of scaffolds were detected by immunofluorescence method. On 7 d after inoculating, the migration of the above two kinds of cells into the two kinds of dermal scaffolds was detected by immunofluorescence and hematoxylin-eosin (HE) staining. Three full-thickness skin defect wounds of 5.0 cm×5.0 cm were created on both sides of the back of three 6-month-old healthy male Ba-Ma mini pigs. According to the random number table, six columns of wounds were divided into type A dermis two-step method group, type B dermis two-step method group, and type B dermis one-step method group. The wounds in type A dermis two-step method group and type B dermis two-step method group were transplanted with type A or type B dermis respectively before, and with autologous split-thickness skin grafting later. The wounds in type B dermis one-step method group were transplanted in a synchronous procedure including type B dermis (without silicone layer) and autologous skin grafting simultaneously. The bleeding, exudation, and infection of the wounds on the back in type A dermis two-step method group and type B dermis two-step method group on the 7th day after the second transplantation and in type B dermis one-step method group on the 14th day after the first transplantation were generally observed. The area of autologous skin graft was measured by the transparent film grid method, and the survival rate of autologous skin was calculated. On 4, 7, and 14 d after the first transplantation, the inflammatory cells, fibroblasts (Fbs), and capillary infiltration into the scaffolds of the three groups were detected by HE staining. On 7, 14 d after the first transplantation, the vascularization of the scaffolds was further observed by immunohistochemistry. On 28, 90 d after the first operation, the degradation of the scaffolds of type A dermis and type B dermis was observed by HE staining. Data were statistically analyzed with one-way analysis of variance, independent sample t test, and Bonferroni correction. Results:A large number of round and oval micropores were evenly distributed on the surface of type A scaffold, and the cylindrical hole walls could be observed arranging in a parallel direction in the longitudinal section. The honeycomb briquette-shaped penetrating macropores on the surface of type B scaffold were arranged in an orderly matrix. The pore walls of the honeycomb briquette-shaped penetrating macropores were connected by micropores to form a network structure. The porosity of type A dermis was (93.21±0.72)%, which was similar to (95.88±1.00)% of type B dermis ( t=4.653, P>0.05). The degradation rates of type A dermis at 4, 8, 13, and 24 h were similar to those of type B dermis at the corresponding time point ( t=0.232, 0.856, 0.258, 7.716, P>0.05). At 24 h after culture, the proliferation rates of L929 cells in the type A dermis group, type B dermis group, and negative control group were significantly higher than those of the positive control group ( t=2 393.46, 2 538.27, 1 077.77, P<0.01). The cytotoxicity rating of cells in positive control group was grade 4, while that of the other three groups was grade zero. On 1, 4, 7, and 14 d after inoculation, both L929 cells and HUVECs proliferated in a time-dependent manner in two kinds of dermal scaffolds. The adhesion growth and proliferation rate of the two kinds of cells on the surface of type B dermis was higher than that of type A dermis. On 7 d after inoculation, both L929 cells and HUVECs covered the surface of type B dermis and migrated into one side of the silicone layer. However, the above two kinds of cells migrated slowly into type A dermis, and only a few cells were found on one side of the silicone layer. There was no bleeding, exudation, or infection in the wounds repaired by type A and type B dermis. The survival rate of autologous skin grafting of 6 wounds in each group was 100%. On 4, 7, and 14 d after the first operation, inflammatory cells, Fbs, and capillaries gradually infiltrated into the scaffold layer, and the cell infiltration rate from high to low was type B dermis one-step method group, type B dermis two-step method group, and type A dermis two-step method group. The scaffold in wound in the type B dermis one-step method group gradually collapsed on 28 d after the first operation, and completely degraded in 3 months after the first operation. The scaffold degradation rate of type A dermis two-step method group was similar to that mentioned above. Conclusions:The honeycomb briquette-shaped vertically penetrating three-dimensional porous network structure of type B scaffold can accelerate its vascularization process, which is beneficial to autogenous split-thickness skin in one-step procedure to repair full-thickness skin defects wound in Ba-Ma mini pigs. Compared with the "two-step method" of staged transplantation of type A scaffold and autologous split-thickness skin, and one-step transplantation has equal efficacy and can provide a better choice for wound treatment.

Objective To investigate the effect of Jinqi Jiangtang tablet on the activation of T helper type 17 (Th17) and the expressions of interleukin (IL)-17 and IL-23 in kidney of diabetic rats. Methods A total of 45 male SD rats were randomly divided into normal control group (NC, n=15) and experimental group (n=30). Diabetes was induced by tail vein injection with streptozotocin (STZ, 45 mg/kg). The well-established 28 diabetic model rats were then randomly divided into diabetes group (DM, n=14) and Jinqi Jiangtang tablet administration group (Jinqi, n=14). The rats in Jinqi group were given Jinqi Jiangtang tablet solution by gavage at a single dose of 2.1 g·kg-1·d-1 for 18 weeks, while NC group and DM group were given 0.9%NaCl in the same way. All rats were sacrificed after 18 weeks. The circulating Th17 frequencies were assessed using flow cytometry. Serum IL-17 and IL-23 levels were measured by enzyme-linked immunosorbent assay. The pathological changes in kidney were studied by electron microscope. The expressions of IL-17 and IL-23 in kidney were detected using immunohistochemistry. Results (1) Compared with the group NC, the circulating Th17 frequencies were significantly increased in group DM and group Jinqi. The circulating Th17 frequencies were significantly lower in group Jinqi than those in group DM. (2) Compared with the group NC, the serum IL-17 and IL-23 levels were significantly increased in group DM and group Jinqi. The serum IL-17 and IL-23 levels were significantly lower in group Jinqi than those in group DM. (3) In group DM, irregular thickening of glomerular basement membrane, fusion of epithelial cell foot processes and mesangial expansion were observed by electron microscope. The above-mentioned pathological changes were improved inthe group Jinqi. (4) Compared with the group NC, the expressions of IL-17 and IL-23 in the renal cortex were significantly increased in group DM and group Jinqi, and those were significantly lower in group Jinqi than those in group DM. Conclusion The activation of Th17 and the increased expressions of IL-17 and IL-23 in kidney play a potential role in diabetic nephropathy. Jinqi Jiangtang tablet can improve diabetic nephropathy through inhibiting the activating Th 17 and decreasing the expression of IL-17 and IL-23 in kidney.

Objective To investigate the therapy effect of fermented cordyceps powder on diabetic cardiomyopathy, and the effect on expressions of NLRP3, Caspase-1 and interleukin (IL)-1βin myocardium of diabetic rats. Methods A total of 45 male SD rats were randomly divided into normal control group (group CON), diabetes group (group DM) and fermented cordyceps powder administration group (group CS, 1 g · kg-1 · d-1). Diabetes rat model was induced by tail vein injection with streptozotocin (45 mg/kg) in group DM and group CS. The rats in group CS were given fermented cordyceps powder solution by gavage at a single dose of 1 g·kg-1·d-1 for 18 weeks. Rats of group CON and group DM were given 0.9%NaCl in the same way. All rats were sacrificed after 18 weeks. The pathological changes in myocardium were observed by HE staining and electron microscope. The expression of NLRP3 in myocardium was detected by Western blotting. The expression levels of NLRP3, Caspase-1 and IL-1βin myocardium were detected by immunohistochemistry. Results (1) Myocardial necrosis and fibrosis and mitochondrial damages were observed under electron microscope in group DM. The above-mentioned pathological changes were improved in the group CS. (2) The result of Western blotting showed that the expression of NLRP3 in myocardium was significantly increased in group DM and group CS than that in group CON, and the expression of NLRP3 was significantly lower in group CS than that in group DM. (3) The result of immunohistochemistry showed that, compared with the group CON, the expressions of NLRP3, Caspase-1 and IL-1β in myocardium were significantly increased in group DM and group CS, and which were significantly lower in group CS than those in group DM. Conclusion Fermented cordyceps powder can improve diabetic cardiomyopathy through decreasing the expressions of NLRP3, Caspase-1 and IL-1βin myocardium.

Objective:To investigate the efficacy and toxicity of oxaliplatin reintroduction combined with raltitrexed as second-line che-motherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients. Methods:The 48 evaluable pa-tients with advanced colorectal cancer following disease progression prior to the first-line chemotherapy were treated with oxaliplatin and raltitrexed (raltitrexed 3 mg/m2 ivgtt d1, oxaliplatin 100-130 mg/m2 ivgtt d1, q21d). All 48 patients were divided into two groups:Group A, non-oxaliplatin-based regimens as the first-line chemotherapy, 20 cases;Group B, oxaliplatin-based regimens as the first-line chemotherapy, 28 cases. Each group was evaluated every two cycles. Results:The response rates (RR) of Groups A and B were 30.0%(6/20) and 32.1%(9/28), the disease control rates (DCR) were 80.0%(16/20) and 75.0%(21/28), the median progression free survival time (mPFS) was 6.5 and 7.0 months, and the median overall survival time (mOS) was 10 and 13 months, respectively. No statistical sig-nificance was observed between the two groups in their RR, CR, mPFS, and mOS (P=0.264, 0.514, 0.713, 0.788), respectively. The most common adverse effects observed wereⅠ-Ⅱgrades of bone marrow suppression, aminotransferase abnormality, and digestive toxici-ties. The incidence of neurotoxicity (Ⅰ-Ⅱgrades) between the two groups was similar. Conclusion:Instead of irinotecan combined with raltitrexed, oxaliplatin reintroduction combined with raltitrexed for second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients is feasible.