Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective To observe the effects of postoperative complications, anal exhaust time, immune function and fatigue index of parenteral and enteral nutrition support after abdominal surgery in elderly patients with malnutrition diagnosed by GLIM criteria. Methods Ninty elderly abdominal surgery patients (more than 70 years old) who diagnosed as malnutrition by GLIM 2-step method were divided into enteral nutrition(EN) group and parenteral nutrition (PN) group randomly. The corresponding immune and fatigue indexes were tested on day 1 and day 7 of postoperation. Postoperative complications, anal exhaust time and mean time of hospitalization were observed and analyzed. Results The incidence of malnutritional risk was 61.0% (122/200) in elderly abdominal surgery patients and malnutrition incidence was 45.0% (90/200). IgA, IgM, IgG, CD3, CD4 and CD4/CD8 on postoperative day 7 increased significantly in EN group than those in PN group (P<0.05). The postoperative complications in EN group significantly lower than that in PN group (P<0.05). Anus exhaust time and hospitalization days of EN group were shorter than that of PN group (P<0.05). Fatigue index on postoperative day 7 of EN group was significantly better than that of PN group (P<0.05). Conclusions The malnutrition diagnosis of elderly patients based on GLIM crteria is a necessary prerequisite for nutritional intervention. Early EN support can reduce postoperative complications and hospitalization days in elderly patients, improve postoperative fatigue syndrome and immune status, and improve the patients with malnutrition recover from surgery.

Objective:To investigate the value of serum vascular endothelial growth factors (VEGF), pepsinogen ratio (PGR) combined with magnifying chromoendoscopy in the diagnosis of Epstein-Barr virus associated gastric carcinoma (EBVaGC).Methods:A retrospective case control study was conducted. The clinical data of 314 patients with gastric cancer who were confirmed by pathological examination in Baoji Central Hospital from January 2018 to January 2023 were retrospectively collected. All patients were divided into EBVaGC group (34 cases) and EB virus negative gastric cancer (EBVnGC) group (280 cases) according to the result of EB virus quantitative real time polymerase chain reaction in serum before treatment, while 50 healthy volunteers who underwent the physical examination in the same period were selected as the control group. The level of VEGF was detected by using enzyme-linked immunosorbent assay (ELISA), and serum levels of pepsinogen (PG) Ⅰ and PGⅡ were detected by using fluorescence immunochromatography. PGR was calculated by PGⅠ-to-PGⅡ ratio. Electronic magnification gastroscopy was performed, suspicious lesions were stained and the pathological state of gastric tissues was observed. Taking the pathological results of living tissues as the gold standard, the diagnostic efficacy of each index alone and the combination detection for EBVaGC was calculated. Multivariate logistic regression model was used to analyze the independent risk factors of the incidence of EBVaGC.Results:The age of patients in EBVaGC group, EBVnGC group and the healthy control group was (61±10) years, (63±12) years and (61±12) years, respectively; and there were 28 males (82.4%), 228 males (81.4%) and 41 males (82.0%), respectively. There were no statistically significant differences in age and gender among the 3 groups (all P>0.05). The serum VEGF level and the proportion of positive patients detected by endochromatography in EBVaGC group were higher than those in the EBVnGC group and the healthy control group [VEGF: (253±48) pg/ml vs. (183±38) pg/ml, (92±25) pg/ml; positive proportion: 94.1% (32/34) vs. 77.9% (218/280), 2.0% (1/50)], and the PGR in EBVaGC group was lower than that in EBVnGC group and the healthy control group (2.1±1.0 vs. 3.1±1.1, 14.1±1.9), and the differences were statistically significant (all P<0.05). The sensitivity of serum VEGF in the diagnosis of EBVaGC was higher than that of PGR [73.5% (25/34) vs. 66.9% (22/34)]. The diagnostic specificity of PGR [78.2% (219/280) vs. 69.3% (194/280)] and accuracy [76.8% (241/314) vs. 69.8% (219/314)] were higher than those of VEGF. The sensitivity [85.3% (29/34)], specificity [82.9% (232/280)] and accuracy [83.1% (261/314)] of magnifying chromoendoscopy in the diagnosis of EBVaGC were higher than those of VEGF and PGR. The sensitivity [94.1% (32/34)], specificity [95.7% (268/280)] and accuracy [95.5% (300/314)] of the 3 combined detection were higher than those of single and pairwise detection. Multivariate logistic regression analysis showed that the independent risk factors for the incidence of EBVaGC included alcoholism ( OR = 2.310, 95% CI: 1.243-3.581, P = 0.007), spicy food preference ( OR = 1.516, 95% CI: 1.084-2.142, P = 0.026), irregular diet ( OR = 1.448, 95% CI: 1.013-2.104, P = 0.043), family history of gastric cancer ( OR = 2.732, 95% CI: 1.312-4.894, P = 0.001). Conclusions:Serum VEGF and PGR combined with magnifying chromoendoscopy can improve the diagnostic efficiency of EBVaGC, and developing good eating will be helpful to prevent or slow down the progression of stomach diseases.

Single-cell multi-Omics(SCM-Omics)and spatial multi-Omics(SM-Omics)technologies provide state-of-the-art methods for exploring the composition and function of cell types in tissues/organs.Since its emergence in 2009,single-cell RNA sequencing(scRNA-seq)has yielded many groundbreaking new discoveries.The combination of this method with the emergence and development of SM-Omics tech-niques has been a pioneering strategy in neuroscience,developmental biology,and cancer research,especially for assessing tumor heterogeneity and T-cell infiltration.In recent years,the application of these methods in the study of metabolic diseases has also increased.The emerging SCM-Omics and SM-Omics approaches allow the molecular and spatial analysis of cells to explore regulatory states and determine cell fate,and thus provide promising tools for unraveling heterogeneous metabolic processes and making them amenable to intervention.Here,we review the evolution of SCM-Omics and SM-Omics technologies,and describe the progress in the application of SCM-Omics and SM-Omics in metabolism-related diseases,including obesity,diabetes,nonalcoholic fatty liver disease(NAFLD)and cardiovascular disease(CVD).We also conclude that the application of SCM-Omics and SM-Omics approaches can help resolve the molecular mechanisms underlying the pathogenesis of metabolic diseases in the body and facilitate therapeutic measures for metabolism-related diseases.This review concludes with an overview of the current status of this emerging field and the outlook for its future.

Objective:To analyze the correlation between 21-gene recurrence score (RS) and clinicopathological characteristics of patients with Lumina type breast cancer, and to explore its significance in individualized treatment.Methods:The clinicopathological data of 59 patients with surgical resection and pathological diagnosis of Lumina type breast cancer in Shanxi Provincial Cancer Hospital from May 2018 to May 2019 were retrospectively analyzed. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of 21 gene and RS was calculated. According to the 21-gene RS, the patients were divided into low recurrence risk group (RS < 18 points), intermediate recurrence risk group (RS 18-31 points) and high recurrence risk group (RS > 31 points). Univariate and multivariate logistic regression analyses were made to evaluate the correlations between different recurrence risk and clinicopathological characteristics of patients and their influence on the choice of adjuvant chemotherapy.Results:Based on the 21-gene RS, 29 patients were in low recurrence risk group, 22 cases were in intermediate recurrence risk group, and 8 cases were in high recurrence risk group. Single-factor analysis showed that age ( P = 0.012), maximum mass diameter ( P = 0.031), histological grade ( P = 0.036), progesterone receptor (PR) level ( P = 0.015), Ki-67 positive index ( P = 0.049) and molecular typing ( P = 0.010) were influencing factors of 21-gene RS recurrence risk. Multivariate logistic regression analysis showed that the age and Ki-67 positive index were negatively correlated with 21-gene RS recurrence risk (both P < 0.05). After grouping according to the 21-gene RS, 17 patients in the intermediate recurrence risk group (according to the traditional postoperative recurrence risk grouping method for breast cancer) were classified as low recurrence risk group, and 4 patients in the low recurrence risk group were classified as intermediate recurrence risk group ( χ2 = 4.535, P = 0.033). After grouping based on 21-gene RS, the number of patients who needed chemotherapy in individualized treatment decreased. Of the 17 cases, 11 cases did not undergo postoperative chemotherapy, and the remaining patients received chemotherapy. The postoperative follow-up period was 11-22 months. As of March 2020, there was no recurrence or disease progress. Conclusion:The 21-gene RS can provide objective basis for the individualized precise treatment and prognosis prediction for patients with early-stage Lumina type breast cancer.

Objective To detect the expression of miR-26a/b in the aorta and serum of mice so as to explore the role of miR-26a/b in vascular remodeling of hypertension.Methods C576L/BJ male mice were randomly divided into AngⅡ group and control group.Mini-osmotic pump was implanted subcutaneously into the back of mice, and the model of blood vessel remodeling in mice was established by continuous infusion of AngⅡ(2.0mg/kg·d).The mice in control group were injected with saline.Blood pressure was taken before the intervention and at 3, 5, 7, 10 and 14 days after the intervention.After 2 weeks, the mice were killed, the serum and aorta tissues were collected, and the expression of miR-26a/b was determined by RT-PCR.HE staining, Masson staining and immunohistochemistry were performed to observe changes in vascular morphology, fibrosis and protein expression.Results After the intervention, systolic blood pressure and diastolic blood pressure were significantly higher in AngⅡ group than in control group (P<0.05).HE staining showed that the vessel wall of AngⅡ group was thicker than that of control group.Masson staining showed more blue collagen deposition in the middle of aorta in AngⅡ group but no obvious collagen deposition in control group.RT-PCR showed that the expression of miRNA-26a/b in the serum and aorta of AngⅡ group was significantly lower than in control group (P<0.05).Immunohistochemistry indicated that the expressions of CTGF, collagen Ⅰ and collagen Ⅲ all increased after AngⅡ infusion (P<0.05).Conclusion MiR-26a/b, CTGF, collagen Ⅰ and collagen Ⅲ may be involved in AngⅡ-induced vascular remodeling in hypertension.MiR-26a/b may be a new therapeutic target of vascular remodeling in hypertension.

Objective To study the effect of dexmedetomidine in the functional endoscopic sinus surgery (FESS) on the recovery period of general anesthesia. Methods Fifteen min before the end of surgery, 40 FESS patients were treated with intravenous infusion of dexmedetomidine at 0.6μg/kg. The occurrence of cough response, degree of pain and agitation in patients were observed. Result The response score of choking cough of the patients with intravenous infusion of dexmedetomiindine was (1.2 ± 0.5), the score of VSA was (1.9 ± 0.5), and the degree of agitation was (1.2 ± 0.4). Conclusion For those undergoing FESS, postoperative use of dexmedetomidine 15 min before the end of surgery, can not only have an effective effect for reducing the incidence of choking cough and agitation and but also decrease the pain degree so that the patients can live through the general anesthesia recovery period.

1 1 patients with moderate or severe crowding in the anterior arch were treated with 4 premolar extraction.After canine distaliza-tion first approach,the teeth were aligned and leveled.The results of the study suggest that,with strict implementation of indication,this method may be a viable treatment for the moderate or severe crowding anterior.

Heart Failure ; genetics ; Humans ; Hypertrophy ; genetics ; MicroRNAs ; genetics