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 investigate the application value of full-length lower extremity CT scans performed at different noise index(NI)in terms of image quality and radiation dose for robot-assisted total knee arthroplasty(RTKA).Methods Eighty patients who underwent RTKA were selected and randomly divided into four groups based on different NI:NI=8,NI=18,NI=28,and NI=38.Subjective scores were assigned to the full-length lower extremity CT images and the three-dimensional skeletal models generated by volume rendering(VR)post-processing.Objective evaluations were performed using three indicators:dose length product(DLP),volume CT dose index(CTDIvol),and hip-knee-ankle angle(HKA).The application value of full-length lower extremity CT scans in RTKA was analyzed.Results(1)As the NI value increased,the subjective scores of thin-slice images decreased.Images with NI between 8 and 18 met the imaging diagnostic standards,while those with NI higher than 18 were unacceptable.(2)As the NI value increased,all VR skeletal models met the acceptance criteria for RTKA.(3)As the NI value increased,DLP and CTDIvol gradually decreased,with statistically significant differences(P<0.05),However,in the comparison between the NI=28 and NI=38 groups,the difference was not statistically significant(P>0.05).Conclusion Performing full-length lower extremity CT scans with an NI of 28 not only meets the preoperative planning requirements for RTKA but also minimizes the radiation dose.

[Objective] To explore the incidence and risk factors of blood transfusion undergoing total knee revision (TKR) using a nationwide database. [Methods] A retrospective data analysis was conducted based on the Nationwide Inpatient Sample (NIS), enrolling patients who underwent TKR from 2015 to 2019 with complete information. Patients under 18 years old and those using anticoagulants, antiplatelets, antithrombotic and non-steroidal were excluded. The patients were divided into two groups based on whether they received blood transfusion or not. The demographic characteristics, length of stay (LOS), total charge of hospitalization, hospital characteristics, hospital mortality, comorbidities and perioperative complications by Wilcoxon rank test for continuous data and chi-square test for categorical data. Logistic regression was performed to identify risk factors of blood transfusion undergoing TKR. [Results] The NIS database included 63 359 patients who underwent TKR. Among them, 5 271 patients received blood transfusion, with an incidence of blood transfusion of 7.8%. There was a decrease in the incidence over the years from 2015 to 2019, dropping from 10.2% to 6.5%. TKR patients requiring transfusions had experienced longer LOS, incurred higher total medical expenses, utilized Medicare more frequently, and had increased in-hospital mortality rates (all P<0.001). Independent risk factors for blood transfusion included female gender, iron-deficiency anemia, rheumatoid disease, collagen vascular disease, chronic blood loss anemia, congestive heart failure, coagulopathy, diabetes with chronic complications, lymphoma, fluid and electrolyte disorders, peripheral vascular disorders, renal failure, valvular disease and weight loss (malnutrition). In addition, risk factors for transfusion in TKR surgery included sepsis, acute myocardial infarction, deep vein thrombosis, gastrointestinal bleeding, heart failure, pneumonia, urinary tract infection, acute renal failure, postoperative delirium, wound infection, lower limb nerve injury, hemorrhage, seroma, hematoma, wound rupture and non healing. [Conclusion] Our findings highlight the importance of recognizing the risk factors of blood transfusion in TKR and establishing corresponding clinical pathways and intervention measures to reduce the occurrence of adverse events.

BACKGROUND:Although obesity is associated with osteoarthritis,it remains unclear whether visceral adipose tissue has a causal relationship with osteoarthritis. OBJECTIVE:To investigate the causal relationship between visceral adipose tissue and osteoarthritis using two-sample Mendelian randomization methods. METHODS:A total of 221 single nucleotide polymorphisms strongly associated with visceral adipose tissue without linkage disequilibrium were screened from the genome-wide association study (GWAS). Pooled data for osteoarthritis were derived from a large genome-wide association analysis that included up to 826690 subjects (177517 osteoarthritis patients and 649173 controls) from nine different populations. We conducted two-sample Mendelian randomization analyses to assess the causal associations between visceral adipose tissue and early-onset any-site osteoarthritis (before age 45),any-site osteoarthritis,knee osteoarthritis,hip osteoarthritis,knee or hip osteoarthritis,spinal osteoarthritis,thumb osteoarthritis,and finger osteoarthritis. Inverse variance weighting was employed as the primary Mendelian randomization analysis method,with weighted median and MR-Egger methods used for supplementary clarification. RESULTS AND CONCLUSION:Inverse variance weighting results revealed a positive causal effect of visceral adipose tissue on eight types of osteoarthritis:early-onset any-site osteoarthritis[odds ratio (OR)=1.91,95％ confidence interval (CI):1.64-2.24,P=6.04×10-16],any-site osteoarthritis (OR=1.44,95％ CI:1.38-1.49,P=3.65×10-75),knee osteoarthritis (OR=1.87,95％ CI:1.75-2.00,P=1.29×10-79),hip osteoarthritis (OR=1.34,95％ CI:1.24-1.45,P=2.84×10-14),knee or hip osteoarthritis (OR=1.71,95％ CI:1.62-1.80,P=2.97×10-83),spinal osteoarthritis (OR=1.42,95％ CI:1.31-1.54,P=8.89×10-17),thumb osteoarthritis (OR=1.26,95％ CI:1.10-1.44,P=6.21×10-4),and finger osteoarthritis (OR=1.29,95％ CI:1.13-1.49,P=2.68×10-4). Sensitivity analyses showed no heterogeneity,pleiotropy,or outliers in the causal effects of visceral adipose tissue on the eight types of osteoarthritis. These findings indicate that visceral adipose tissue is a risk factor of osteoarthritis,and excessive visceral adipose tissue may increase the risk of osteoarthritis.

Objective To investigate the application value of full-length lower extremity CT scans performed at different noise index(NI)in terms of image quality and radiation dose for robot-assisted total knee arthroplasty(RTKA).Methods Eighty patients who underwent RTKA were selected and randomly divided into four groups based on different NI:NI=8,NI=18,NI=28,and NI=38.Subjective scores were assigned to the full-length lower extremity CT images and the three-dimensional skeletal models generated by volume rendering(VR)post-processing.Objective evaluations were performed using three indicators:dose length product(DLP),volume CT dose index(CTDIvol),and hip-knee-ankle angle(HKA).The application value of full-length lower extremity CT scans in RTKA was analyzed.Results(1)As the NI value increased,the subjective scores of thin-slice images decreased.Images with NI between 8 and 18 met the imaging diagnostic standards,while those with NI higher than 18 were unacceptable.(2)As the NI value increased,all VR skeletal models met the acceptance criteria for RTKA.(3)As the NI value increased,DLP and CTDIvol gradually decreased,with statistically significant differences(P<0.05),However,in the comparison between the NI=28 and NI=38 groups,the difference was not statistically significant(P>0.05).Conclusion Performing full-length lower extremity CT scans with an NI of 28 not only meets the preoperative planning requirements for RTKA but also minimizes the radiation dose.

BACKGROUND:Although obesity is associated with osteoarthritis,it remains unclear whether visceral adipose tissue has a causal relationship with osteoarthritis. OBJECTIVE:To investigate the causal relationship between visceral adipose tissue and osteoarthritis using two-sample Mendelian randomization methods. METHODS:A total of 221 single nucleotide polymorphisms strongly associated with visceral adipose tissue without linkage disequilibrium were screened from the genome-wide association study (GWAS). Pooled data for osteoarthritis were derived from a large genome-wide association analysis that included up to 826690 subjects (177517 osteoarthritis patients and 649173 controls) from nine different populations. We conducted two-sample Mendelian randomization analyses to assess the causal associations between visceral adipose tissue and early-onset any-site osteoarthritis (before age 45),any-site osteoarthritis,knee osteoarthritis,hip osteoarthritis,knee or hip osteoarthritis,spinal osteoarthritis,thumb osteoarthritis,and finger osteoarthritis. Inverse variance weighting was employed as the primary Mendelian randomization analysis method,with weighted median and MR-Egger methods used for supplementary clarification. RESULTS AND CONCLUSION:Inverse variance weighting results revealed a positive causal effect of visceral adipose tissue on eight types of osteoarthritis:early-onset any-site osteoarthritis[odds ratio (OR)=1.91,95％ confidence interval (CI):1.64-2.24,P=6.04×10-16],any-site osteoarthritis (OR=1.44,95％ CI:1.38-1.49,P=3.65×10-75),knee osteoarthritis (OR=1.87,95％ CI:1.75-2.00,P=1.29×10-79),hip osteoarthritis (OR=1.34,95％ CI:1.24-1.45,P=2.84×10-14),knee or hip osteoarthritis (OR=1.71,95％ CI:1.62-1.80,P=2.97×10-83),spinal osteoarthritis (OR=1.42,95％ CI:1.31-1.54,P=8.89×10-17),thumb osteoarthritis (OR=1.26,95％ CI:1.10-1.44,P=6.21×10-4),and finger osteoarthritis (OR=1.29,95％ CI:1.13-1.49,P=2.68×10-4). Sensitivity analyses showed no heterogeneity,pleiotropy,or outliers in the causal effects of visceral adipose tissue on the eight types of osteoarthritis. These findings indicate that visceral adipose tissue is a risk factor of osteoarthritis,and excessive visceral adipose tissue may increase the risk of osteoarthritis.

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.

Genicular nerve block is usually used for the treatment of chronic pain of knee osteoar-thritis,which can effectively relieve knee pain and preservemotor function.With the rapid development of ultrasound technology,ultrasound-guided genicular nerve block can improve the accuracy of nerve block and reduce block-related complications.This article reviews the research progress of ultrasound-guided genicular nerve block in three aspects:anatomy,operation methods and clinical application.

The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.

Mycoplasma capricolum subsp. capripneumoniae (Mccp) is the cause of contagious caprine pleuropneumonia (CCPP) in goats. Inactivated vaccines and capsular polysaccharide (CPS) indirect hemagglutination reagents are available for prevention and serological detection, but high culture costs and complex antigen quantification have been plagued by production staff. In order to solve these problems in production practice, a sugar fermentation medium with an initial pH value of 7.8, which could improve the production of two antigens simultaneously, was screened out by changing the initial pH value based on previous Mccp metabolomics analysis. Since phenol red can be identified by UV absorption spectrum and cetyltrimethylammonium bromide (CTAB) can bind to anionic capsular polysaccharide, a UV spectrum measurement method for analyzing the culture stage reached by Mccp and a CTAB precipitation test for relative quantification of capsular polysaccharide antigen content in the fermentation broth were established. The UV spectrum observation method can guide the production of Mccp according to the growth curve of Mccp, which greatly reduces the monitoring time of the traditional CCU method and improves the accuracy of the original eye-observation method. The established CTAB precipitation test can complete the monitoring of CPS content within 5 hours, which greatly reduces the time required compared with the traditional differential technique, and its accuracy was verified by the phenol-sulfuric acid method. The optimized culture medium and the two correlation comparison methods established in this study can effectively reduce the production cost of Mccp and improve the production efficiency. The two assays have been used in the research at our laboratory, which provides experimental data for further improvement of the production process of CCPP inactivated vaccine and capsular polysaccharide as well as rapid quantification.
Humans ; Animals ; Goats ; Cetrimonium ; Mycoplasma ; Polysaccharides