Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.

Objective:To explore the correlation between serum microRNA(miR)-124 and miR-181c expression and the treatment outcome of Solitaire stent thrombectomy in patients with acute cerebral infarction and its influencing factors.Methods:Eighty-one patients with acute cerebral infarction performed Solitaire stent thrombectomyfrom June 2018 to October 2020 in the Affiliated Hospital of Jining Medical College were selected. The predictive value of miR-124, miR-181c expression in patients with acute cerebral infarction were analyzed.Results:In 81 patients, 21 patients with poor outcome(poor outcome group) and 60 patients with favorable outcome (favorable outcome group). The ratio of age ≥ 60 years in poor outcome group was higher than that in the favorable outcome group: 76.19% (16/21) vs. 46.67% (28/60), there was statistical difference ( χ2 = 5.46, P<0.05). The levels of miR-124, miR-181c before surgery and postoperative 1-day, 7-day in the favorable outcome group were higher than those in poor outcome group: 2.81 ± 0.82 vs. 2.24 ± 0.74, 3.01 ± 1.52 vs. 2.07 ± 1.04, 3.25 ± 1.67 vs. 1.86 ± 0.92; and the levels of miR-181c before surgery and postoperative 1-day, 7-day in the favorable outcome group were lower than those in the poor outcome group: 1.43 ± 0.59 vs. 1.79 ± 0.65, 1.35 ± 0.62 vs. 1.94 ± 0.79, 1.24 ± 0.60 vs. 2.16 ± 1.08, there were statistical differences ( P<0.05). The results of Logistic multivariate analysis showed that the age, the levels of miR-124, miR-181c before operation and postoperative 1-day, 7-day were influencing factors for the treatment outcome of Solitaire stent thrombectomy. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-124, miR-181c on the postoperative 7-day were 0.806, 0.861, and were higher than those before operation and the postoperative 1-day, the diagnostic sensitivity were 71.43%, 76.19%, the specificity were 88.33%, 85.00%. Conclusions:The expression of miR-124 and miR-181c in the serum of acute cerebral infarction is related to the outcome of Solitaire stent thrombectomy, especially the expression level on the postoperative 7-day has better application value. It can be used to predict the outcome of surgery.

Objective:To investigate the correlation between serum brain-derived neurotrophic factor (BDNF) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke, and to evaluate its predictive value for PSCI.Methods:Patients with acute ischemic stroke admitted to the Affiliated Hospital of Jining Medical University from April 2018 to September 2020 were prospectively enrolled. Cognitive impairment was assessed by Montreal Cognitive Assessment (MoCA) at 3 months after onset. Multivariate logistic analysis was used to determine the independent correlation between serum BDNF and PSCI, and receiver operating characteristics (ROC) curve was used to evaluate its predictive value for PSCI. Results:A total of 511 patients with acute ischemic stroke were enrolled, including 332 males (65.0%), aged 60.67±10.18 (range 49-80) years. The median score of the National Institutes of Health Stroke Scale (NIHSS) at the baseline was 5.0 (interquartile range 2.7-6.7), and 413 patients (80.8%) had anterior circulation stroke. The median of serum BDNF was 11.54 μg/L (interquartile range 6.13-16.25 μg/L). PSCI occurred in 310 patients (60.7%). Univariate analysis showed that there were significant differences in age, history of previous transient ischemic attack, baseline NIHSS score and serum BDNF between the PSCI group and the non-PSCI group (all P<0.05). Multivariate logistic analysis showed that there was a significant independent correlation between serum BDNF and PSCI (odds ratio 0.514, 95% confidence interval 0.356-0.807; P=0.005). ROC curve analysis showed that the area under the curve of serum BDNF predicting PSCI was 0.863 (95% confidence interval 0.830-0.896; P<0.001). The best cut-off value was 10.78 μg/L, and the sensitivity and specificity were 74.9% and 86.8% respectively. Conclusion:Higher baseline serum BDNF was a protective factor for PSCI and had good predictive value for PSCI.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that can regulate the immune response. They play an important role in the formation and progression of tumors and can suppress immune response in infections and inflammatory diseases. In recent years, MDSC have attracted a lot of attention in the field of tumor immunology, especially in solid tumors, but little is known about the role in hematological tumors. In this paper, the characteristics, functions and related clinical researches of MDSC in hematological tumors including multiple myeloma (MM), lymphoma, leukemia, and myelodysplastic syndrome (MDS) will be summarized to provide new ideas for the treatment of hematologic system tumors.

Compared with distal gastrectomy, pylorus-preserving gastrectomy is less invasive which can decrease incidence of dumping syndrome, diarrhea and body weight lost, cholecystitis and gallstone, reflux gastritis and esophagitis and remnant gastric cancer. Based on new Japanese Gastric Cancer Treatment Guideline and new progression in the world, we give a review mainly basic characteristics, indications, operation details and short- and long-time outcomes after pylorus-preserving gastrectomy.
Gastrectomy ; methods ; Gastric Stump ; pathology ; Gastroenterostomy ; Humans ; Organ Sparing Treatments ; Pylorus ; surgery ; Stomach Neoplasms ; surgery

Objective To observe the effects of sevoflurane inhalation anesthesia and spinal canal anesthesia on cogni-tive function in patients with urinary surgery in the elderly. Methods Researched 68 patients that undergoing elective urinary surgery in elderly patients, and then randomly divided into the sevoflurane inhalation anesthesia group (group A) and spinal canal anesthesia group (group B). The two groups were recorded time of anesthesia operation, surgical blood loss and transfusion volume, low blood pressure and the number of hypoxemia occurred, at last used the simple mental state examination (MMSE) to evaluate two groups of patients with 1 d before anesthesia and postoperative 1 d, 3 d, 7 d cognitive function. Results Two groups of anesthesia operation in time, surgical blood loss and transfusion volume, low blood pressure and the number of hypoxemia occurred had no significant differences(P>0.05). Two groups of postoper-ative 1 d, 3 d MMSE score were significantly lower than before operation, and the group A was significantly lower than group B, the differences were statistically significant(P <0.05);MMSE of A group ofter treatment for 7days were signifi-cantly lower than before the operation, but there was no significant difference compared with controls of groupA ofter treatment for 7 days (P>0.05); The incidence of POCD postoperative 1 d and 3 d in groupA were significantly higher than that of group B, with significant difference (P<0.05), and the incidence of POCD difference of two groups of post-operative 7 d was not significant (P >0.05). Conclusion Sevoflurane inhalation anesthesia is spinal canal anesthesia cognitive dysfunction occurred more often in patients with elderly urinary surgery.