Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Objective:To explore the correlations between the monocytes/high-density lipoprotein ratio (MHR), alkaline phosphatase (ALP), and all-cause mortality in patients undergoing maintenance peritoneal dialysis (PD), and to provide references for clinical prevention and treatment strategies.Methods:A retrospective analysis was conducted on the clinical data of 336 PD patients who were treated in the Affiliated Hospital of Jining Medical University from June 2014 to August 2023. According to the survival status of the patients during the follow-up period, they were divided into the death group ( n=55) and the survival group ( n=281). The differences in clinical data, blood routine, laboratory biochemical indicators, monocyte count, high-density lipoprotein cholesterol, and ALP indicators between the two groups were collected and compared. Multivariate Cox regression analysis was used to screen the risk factors for all-cause mortality in PD patients, and Pearson correlation analysis was used to evaluate the correlation between the survival time of patients and related indicators. Results:In this study, there were 55 patients who died of all causes. The causes of death were cardiovascular events in 26 cases (47.27%), gastrointestinal bleeding in 3 cases (5.45%), infection in 7 cases (12.73%), multiple organ failure in 8 cases (14.55%), and unexplained death in 11 cases (20.00%). There was no statistically significant difference in gender, age, weight, serum parathyroid hormone (PTH), and total cholesterol (TC) between the death group and the survival group (all P>0.05). The treatment time, neutrophil count, red blood cell volume distribution width (RDW), ALP, blood uric acid (UA), blood calcium, MHR and creatinine in the death group were all higher than those in the survival group (all P<0.05), while the lymphocyte count was lower than that in the survival group ( P<0.05). The Cox risk model showed that MHR, ALP, treatment duration, neutrophil count, lymphocyte count, RDW, UA, and creatinine were independent risk factors for all-cause mortality in PD patients ( OR=1.578, 2.881, 1.021, 1.122, 1.476, 2.231, 1.018, 1.008, all P<0.05); Pearson correlation analysis revealed that the survival time of PD patients was negatively correlated with MHR and ALP ( r=-0.305, -0.246, all P<0.05). Conclusions:The levels of MHR and ALP are closely related to the risk of all-cause mortality in PD patients and are independent risk factors for all-cause mortality in patients.

Objective:To explore the correlations between the monocytes/high-density lipoprotein ratio (MHR), alkaline phosphatase (ALP), and all-cause mortality in patients undergoing maintenance peritoneal dialysis (PD), and to provide references for clinical prevention and treatment strategies.Methods:A retrospective analysis was conducted on the clinical data of 336 PD patients who were treated in the Affiliated Hospital of Jining Medical University from June 2014 to August 2023. According to the survival status of the patients during the follow-up period, they were divided into the death group ( n=55) and the survival group ( n=281). The differences in clinical data, blood routine, laboratory biochemical indicators, monocyte count, high-density lipoprotein cholesterol, and ALP indicators between the two groups were collected and compared. Multivariate Cox regression analysis was used to screen the risk factors for all-cause mortality in PD patients, and Pearson correlation analysis was used to evaluate the correlation between the survival time of patients and related indicators. Results:In this study, there were 55 patients who died of all causes. The causes of death were cardiovascular events in 26 cases (47.27%), gastrointestinal bleeding in 3 cases (5.45%), infection in 7 cases (12.73%), multiple organ failure in 8 cases (14.55%), and unexplained death in 11 cases (20.00%). There was no statistically significant difference in gender, age, weight, serum parathyroid hormone (PTH), and total cholesterol (TC) between the death group and the survival group (all P>0.05). The treatment time, neutrophil count, red blood cell volume distribution width (RDW), ALP, blood uric acid (UA), blood calcium, MHR and creatinine in the death group were all higher than those in the survival group (all P<0.05), while the lymphocyte count was lower than that in the survival group ( P<0.05). The Cox risk model showed that MHR, ALP, treatment duration, neutrophil count, lymphocyte count, RDW, UA, and creatinine were independent risk factors for all-cause mortality in PD patients ( OR=1.578, 2.881, 1.021, 1.122, 1.476, 2.231, 1.018, 1.008, all P<0.05); Pearson correlation analysis revealed that the survival time of PD patients was negatively correlated with MHR and ALP ( r=-0.305, -0.246, all P<0.05). Conclusions:The levels of MHR and ALP are closely related to the risk of all-cause mortality in PD patients and are independent risk factors for all-cause mortality in patients.

Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.

Objective:To investigate the relationship between serum osteopontin (OPN), bone morphogenetic protein 2 (BMP2), retinol binding protein 4 (RBP4) and renal function and bone mineral density in patients with diabetes nephropathy (DN).Methods:A total of 120 patients with DN diagnosed in the Affiliated Hospital of Jining Medical University from January 2020 to December 2021 were selected as the DN group, 60 patients with simple diabetes as the type 2 diabetes mellitus (T2DM) group, and 60 subjects with normal glucose tolerance test as the control group. The serum OPN, BMP2, RBP4, low bone mineral density (LBMD), femoral neck bone density (FNBMD) and renal function indicators of the three groups were compared. According to the urinary albumin excretion rate (UAER) of DN patients, the patients were divided into microalbuminuria DN group (71 cases) and massive albuminuria DN group (49 cases), and stratified comparison was made. The simple linear correlation analysis was used to analyze the OPN of DN patients. BMP2, RBP4, renal function and bone mineral density.Results:The fasting blood glucose (FPG), glycated hemoglobin (HbA 1c), serum creatinine (Scr), UAER, and cystatin (CysC) levels of DN group patients were significantly higher than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The FPG and HbA 1c in the T2DM group were higher than those in the control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of DN group patients were higher than those of T2DM group and control group, while the RBP4, LBMD, FNBMD of DN group were lower than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of the T2DM group were higher than those of the control group, while RBP4 was lower than that of the control group, and the differences were statistically significant (all P<0.05); The levels of FPG, HbA 1c, Scr, UAER, and CysC in patients with macroalbuminuria DN were significantly higher than those in patients with microalbuminuria DN, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of patients in the large albuminuria DN group were higher than those in the microalbuminuria DN group, while the RBP4, LBMD, and FNBMD of patients in the large albuminuria DN group were lower than those in the microalbuminuria DN group, and the differences were statistically significant (all P<0.05). The OPN of DN group patients was positively correlated with Scr, UAER, and CysC (all P<0.05), while BMP2 was positively correlated with UAER and CysC (all P<0.05); The OPN and BMP2 of DN group patients were negatively correlated with LBMD and FNBMD (all P<0.05), while RBP4 was positively correlated with LBMD and FNBMD (all P<0.05). Conclusions:OPN, BMP2, RBP4 are closely related to the degree of renal function impairment and bone loss in DN patients, and can to some extent reflect the degree of bone metabolism and osteoporosis in T2DM patients.

[Objective]Childhood trauma(CT)is considered one of the major risk factors for developing major depres-sive disorder(MDD)in adulthood.However,the neural basis of MDD patients with CT(CT-MDD)remains poorly under-stood.Therefore,the objective of our study is to explore the resting-state global brain functional connectivity(FC)in CT-MDD.[Methods]A total of 34 CT-MDD and 34 healthy controls performed resting-state fMRI.Whole-brain voxel-level degree centrality(DC)analysis was performed,and the brain regions with significant differences between the two groups were selected as region of interest(ROI)for further estimating the global brain FC.Subsequently,correlation analysis was performed between DC values,FC values in abnormal brain areas and clinical characteristics.[Results]The CT-MDD group showed increased DC value of the right middle frontal gyrus(MFG)compared with the healthy controls.Seed-based FC revealed that the CT-MDD group showed increased connections between the left precuneus and the right MFG or the right medial prefrontal cortex,relative to healthy controls(threshold at P<0.05).Additionally,the DC value of the right MFG was correlated with the severity of CT.[Conclusion]Our results show the increased FC between the left precuneus and the ROI(right MFG)as well as the right medial prefrontal cortex,which are two important brain regions within the de-fault mode network(DMN),and might suggest increased synchronism between the cognitive executive networks and DMN in CT-MDD.These findings may provide insights into the pathophysiological mechanisms underlying CT-MDD.

Peritoneal dialysis is a recognized renal replacement therapy. Long term peritoneal dialysis will lead to changes in the morphology and function of the peritoneum, that is, peritoneal fibrosis, which is a known cause of the loss of peritoneal ultrafiltration capacity. Pyroptosis is a special type of soluble programmed cell death, characterized by cell swelling, rupture, secretion of cell contents and significant proinflammatory effect. The pyroptosis can be divided into typical and atypical pathways, and the inflammatory body of NOD like receptor heat protein domain related protein 3 (NLRP3) is the most important initiator. Current evidence shows that high glucose peritoneal dialysis fluid can induce peritoneal Mesothelium to scorch, and the inflammation and cell damage caused by it can aggravate the progress of peritoneal fibrosis. Different signal pathways have been proved to regulate the occurrence of pyroptosis. The latest research has proved that some potential targeted methods to inhibit pyroptosis can effectively inhibit the inflammation of peritoneal mesothelium and alleviate peritoneal fibrosis. This article mainly discusses the molecular mechanism of pyroptosis and the relationship between pyroptosis and peritoneal fibrosis.

Objective:To explore the application effect of quantitative evaluation nursing in Operating Room in patients undergoing radical resection of rectal cancer.Methods:A total of 114 patients who received radical resection of rectal cancer in Xi'an Daxing Hospital from December 2019 to December 2021 were selected by the convenient sampling method. According to the order of admission, they were divided into the observation group and the conventional group, with 57 cases in each group. The observation group received quantitative evaluation nursing in the Operating Room, while the conventional group received routine Operating Room nursing. The differences in physiological indexes and mood state scores were compared between the two groups.Results:The postoperative diastolic blood pressure, systolic blood pressure and heart rate in the observation group were lower than those in the conventional group ( P<0.05). The scores of depression-frustration, tension-anxiety, fatigue-dullness, anger-hostility and confusion-chaos dimensions of postoperative mood state in the observation group were lower than those in the conventional group, and the energy-vitality score was higher than that in the conventional group ( P<0.05) . Conclusions:Quantitative evaluation nursing in the Operating Room can reduce the psychosomatic stress response in patients undergoing radical resection of rectal cancer.

Objective:To investigate the correlation between serum microRNA (miR)-15a-5p and prognosis, neoadjuvant chemotherapy (NAC) response in patients with locally advanced gastric cancer (LAGC).Methods:The clinical data of 122 patients with LAGC who underwent surgery after NAC in Eastern Theater Air Force Hospital of the Chinese People′s Liberation Army from May 2016 to April 2020 were analyzed retrospectively. The general clinical data and laboratory examination results of the patients were recorded. The expression level of serum miR-15a-5p was detected by real-time fluorescence quantitative polymerase chain reaction, and the relationship between the expression of miR-15a-5p and different clinical characteristics in patients with LAGC was analyzed. The pathological response was evaluated by Becker tumor regression grading, in which patients with grade 1a, 1b and 2 were sensitive group and patients with grade 3 were resistant group.Results:The patients with LAGC were divided into high expression (>1.038) and low expression (≤1.038) according to the median miR-15a-5p of 1.038 with 61 cases each. The expression level of serum miR-15a-5p was related to the preference for spicy food, endoscopic ultrasonography (EUS)-T stage and EUS-N stage ( P<0.01 or <0.05). According to the evaluation result of pathological reaction, there were 47 cases in resistance group and 74 cases in sensitive group. The serum miR-15a-5p in resistance group was significantly higher than that in sensitive group: 1.69 (1.39, 1.97) vs. 0.99 (0.96, 1.02), and there was statistical difference ( Z =-8.55, P<0.01). The receiver operating characteristic curve analysis result showed that the area under the curve of serum miR-15a-5p predicting NAC response was 0.959 (95% CI 0.929 to 0.990), the optimal cut-off value was 1.049, the sensitivity was 100.0%, and the specificity was 85.1%. Multivariate Logistic regression analysis result showed that miR-15a-5p was an independent risk factor for NAC response in patients with LAGC ( HR = 1 880.840, 95% CI 123.510 to 28 641.846, P<0.01). Kaplan-Meier survival curve analysis result showed that the median overall survival time and median progression free survival time in patients with high expression of miR-15a-5p were significantly shorter than those in patients with low expression of miR-15a-5p (19 months vs. 62 months and 12 months vs. 51 months), and there were statistical differences (log-rank χ2 = 41.99 and 61.97, P<0.01); the 10-year overall survival rate and 10-year progression free survival rate in patients with high expression of miR-15a-5p were significantly lower than those in patients with low expression of miR-15a-5p (4.9% vs. 52.5% and 24.6% vs. 85.2%), and there were statistical differences (log-rank χ2 = 33.70 and 45.32, P<0.01). Multivariate Cox regression analysis result showed that R 0 resection and miR-15a-5p were the independent risk factors affecting the overall survival time and progression free survival time in patients with LAGC (overall survival time: HR = 1.945 and 3.487, 95% CI 1.033 to 3.660 and 2.112 to 5.759, P<0.05 or <0.01; progression free survival time: HR = 2.427 and 6.335, 95% CI 1.069 to 5.510 and 3.341 to 12.013, P<0.05 or <0.01). Conclusions:The increase of serum miR-15a-5p level is related to NAC response and poor prognosis in patients with LAGC. It can be used as a reliable biomarker to predict the prognosis and NAC response of LAGC.