ABSTRACT
Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.
ABSTRACT
Objective:To investigate the effects of different labeling conditions on the yield of Al 18F-labeled 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA)-prostate specific membrane antigen (PSMA)-137, and to determine the experimental condition for obtaining Al 18F-PSMA-137 probe in high yield. Methods:The effects of different pH values, buffer systems (acetic acid-sodium acetate buffer system and potassium hydrogen phthalate (KHP) buffer system), AlCl 3-ligand ratios, ligand amounts, ethanol volumes and reaction temperatures on the labeling rate were investigated in detail. Results:The pH value of the reaction solution had a significant effect on the labeling rate, and the optimal range was 4.0-4.5. When the pH value was higher than 4.5, the labeling rate decreased significantly. Both the acetic acid-sodium acetate buffer system and the KHP buffer system could be used to label NOTA-PSMA-137 with Al 18F, and the KHP buffer system obtained higher labeling rate. The ratio of AlCl 3-ligand affected the labeling rate, and the highest labeling rate could be obtained when the ratio of AlCl 3-ligand was 0.54-0.62. When the ratio of AlCl 3-ligand was fixed, increasing the amount of ligand could improve the labeling yield. Adding hydrophilic organic solvent ethanol to the reaction system could significantly increase yield, with the highest labeling rate being achieved at a volume of 100 μl ethanol. The most suitable reaction temperature was 100 ℃, and when the temperature raised to 110 ℃, the labeling rate decreased significantly. The most suitable labeling conditions for NOTA-PSMA-137 were as following: 25 μl KHP buffer (0.50 mol/L, pH=4.0), 7.0 μl AlCl 3 solution (20 mmol/L), 200 μl Na 18F solution (74-80 MBq) and 230 μg ligand NOTA-PSMA-137 were mixed in a vial, then stood for 5 min and 100 μl ethanol was added, and all reagents were heated at 100 ℃ for 10 min. The yield of Al 18F-PSMA-137 under above conditions were 85.7%-88.5%. Conclusion:Optimization of labeling condition can improve the yield of Al 18F-PSMA-137 and the stability of the labeling.
ABSTRACT
Hepatic fibrosis is present in most chronic liver disease processes, and there are no ideal anti-fibrotic drugs available. Astragalus has a long history of medicinal use, and its anti-fibrotic effects have been confirmed by modern studies. In this study we have searched the literature to identify the signaling pathways and mechanisms of action of Astragalus and its active ingredients on hepatic fibrosis in recent years, so as to provide the basis and ideas for the development of anti-fibrotic drugs and mechanisms of Astragalus. It is showed that the active ingredients of Astragalus act through regulating p38MAPK, TGF-pl/Smads,NF-
ABSTRACT
Tibet orbivirus (TIBOV) was identified as a novel orbivirus in 2014. Antibodies against TIBOV were detected in cattle, Asian buffalo, and goats, while all the sequenced TIBOV strains were isolated from mosquitos and Culicoides. The known TIBOV strains have been classified into four putative serotypes. In this study, two TIBOV strains isolated from Culicoides spp. in Shizong County of Yunnan Province, China, were fully sequenced. The phylogenetic analysis of outer capsid protein 2 (VP2) indicated that these two viral strains belong to two novel putative serotypes of TIBOV. The updated putative serotypes may help in an investigation of the distribution and virulence of TIBOV.
ABSTRACT
Objective@#To examine breakfast consumption among primary school students in grades 4 and 5 in Qinghai Province, China, and to provide evidence for nutrition education and intervention strategies.@*Methods@#We used a multistage stratified cluster random sampling method to select the participants. A total of 969 students were selected from 10 primary schools in four counties and districts of three cities, namely Haidong City, Hainan Prefecture and Haixi Prefecture in Qinghai Province. A self rated questionnaire was administered to investigate breakfast consumption.@*Results@#The proportion of students who consumed breakfast 5 to 7 times per week, 3 or 4 times per week, and 1 or 2 times per week were 82.0%, 9.7%, and 6.7%, respectively, while 1.5% never ate breakfast. In descending order, the breakfast food types consumed were cereals and tubers; milk, legumes and nuts; vegetables and fruits; fish and poultry; and meat and eggs (84.1%, 69.8%, 66.8%, and 37.7%, respectively). The proportion of vegetables and fruits in the breakfast of grade 5 students was higher than that of grade 4 students( χ 2=4.81, P = 0.03 ), the proportion of fish, poultry,meat and eggs in county urban areas was higher than that of students in rural( χ 2=6.94, P =0.03), while the proportion of vegetables and fruits in urban areas was lower than that of students in suburban areas( χ 2=53.33, P <0.01). The proportion of breakfast food containing fish,poultry,meat and eggs of boarding students was higher than that of non boarding students( χ 2=41.26, P <0.01), while the proportion of breakfast food containing vegetables and fruits, milk & legumens & nuts was lower than that of non-boarding students( χ 2=21.11, 4.41, P <0.01). A total of 44.8% of students had a poor quality breakfast, and only 16.3% had a good quality breakfast. Moreover, 47.5% of breakfasts were prepared by mothers, followed by the school canteen which prepared 29.9%. Except for students in different grades, there were statistically significant differences in the distribution of breakfast preparers in other groups( P <0.05).@*Conclusion@#In Qinghai Province,breakfast skipping is observed in some senior primary school students, and the quality of breakfast is poor. Diet and nutrition education should be provided for students, parents, and school canteen staff to improve the frequency and nutritional quality of children s breakfasts.
ABSTRACT
Objective@#To understand the current situation regarding snack food consumption among grade 4 and grade 5 primary school students in agricultural and pastoral areas of Qinghai Province, China, and to provide a scientific basis for nutrition education and intervention strategies.@*Methods@#Multistage stratified cluster random sampling was employed. The research included 969 fourth and fifth grade students were selected from 10 primary schools in four counties and districts of three cities in Haidong City, Hainan Prefecture and Haixi Prefecture in Qinghai Province. The self report questionnaire method was used to investigate the current status regarding snack food consumption in this population.@*Results@#The proportion of students who consumed snack food at home, school and elsewhere were 98.2%, 88.5% and 75.4%, respectively. Male students reported a lower rate of snack consumption at school than female students ( χ 2=9.66). The fifth grade students reported a higher rate of snack consumption at home and other places than the fourth grade students ( χ 2=10.31, 6.77). The reported rate of snack consumption of students in the rural was higher than that in the county( χ 2=6.03,100.53, 24.77). The reported rate of snack consumption of boarding students at home was lower than that of non-boarding students ( χ 2=7.22), while the reported rate of snack consumption at school was higher than that of non-boarding students ( χ 2=9.04）（ P <0.01). The most popular snacks consumed at home included fruits and vegetables, cereals and nuts (76.9%, 67.2%, 63.7%), while the most popular snacks consumed at school were fruits and vegetables, cereals and candies (45.1%, 36.9%, 24.4%). The most popular snacks consumed in other settings included ice cream, candies and beverages(54.7%, 51.6%, 42.9%). The top three reasons for snacking were that snacks were regarded as delicious, healthy/nutritious and clean (76.9%, 65.5% and 59.0%, respectively).@*Conclusion@#Snacking is popular among students, although many snacks are unhealthy. Therefore, there is a need to improve food environments and nutrition education, so as to help students to choose healthy beverages and adopt healthy eating behaviors.
ABSTRACT
Hepatic fibrosis is a pathological reparative response of the liver to chronic injury and a crucial step in the progression of chronic liver disease， characterized mainly by the activation of hepatic stellate cells and diffuse deposition of extracellular matrix. Currently， there is no ideal specific drug for the treatment of liver fibrosis in clinical practice. In recent years， with the development and progress of traditional Chinese medicine （TCM） in the treatment of liver fibrosis， TCM has been widely recognized for its significant therapeutic effect and fewer adverse reactions. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is an important pathway that affects the formation and development of liver fibrosis. It mainly plays a role in liver fibrosis by inhibiting the activation and proliferation of hepatic stellate cells， promoting their apoptosis， reducing oxidative stress in liver cells， decreasing the deposition of extracellular matrix， and enhancing liver cell autophagy. This article summarized the mechanisms by which Chinese medicinal monomers regulated the PI3K/Akt pathway to exert their effects on liver fibrosis and their synergistic effects with other signaling pathways， providing a theoretical basis and references for the development of new drugs for the treatment of liver fibrosis with TCM.
ABSTRACT
Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.
Subject(s)
Humans , Occupational Exposure/adverse effects , Health StatusABSTRACT
Hepatocellular carcinoma （HCC） is one of the common malignant tumors of the digestive tract and seriously threatens the life of patients due to a high incidence rate， a high degree of malignancy， strong invasion and metastasis， and poor prognosis. At present， the main methods for the prevention and treatment of HCC include drugs， surgery， and interventional treatment， but all of these methods have certain adverse reactions and side effects. As an important intracellular signal transduction pathway in the human body， the JAK/STAT signaling pathway mainly exerts an anti-HCC effect by regulating cell invasion， metastasis， proliferation， growth， apoptosis， autophagy， angiogenesis， inflammation/immune response， iron metabolism， and drug resistance. Therefore， targeting the JAK/STAT signaling pathway plays an important role in the prevention and treatment of the development and progression of HCC. Traditional Chinese medicine has attracted wide attention due to its advantages of multiple targets， pathways， components， and levels in the treatment of HCC， and many cell or animal experiments on traditional Chinese medicine in the treatment of HCC have shown that the JAK/STAT signaling pathway is an important target for the prevention and treatment of HCC， with the effects of improving liver function， reducing HCC recurrence， and improving immunity. Based on this， this article analyzes the mechanism of action of the JAK/STAT signaling pathway in HCC， as well as the intervention effect of traditional Chinese medicine monomers， traditional Chinese medicine extracts， and traditional Chinese medicine compounds on the JAK/STAT signaling pathway， in order to provide theoretical basis and reference for the prevention and treatment of HCC and the research and development of new traditional Chinese medicine drugs.
ABSTRACT
OBJECTIVES@#To investigate the differences in non-suicidal self-injury (NSSI) behaviors between only-child and non-only-child adolescents with mood disorders.@*METHODS@#A three-stage sampling method was used to perform a cross-sectional survey of 529 adolescents, aged 12-18 years, who had mood disorders and NSSI behaviors. These adolescents were sampled from the outpatient service of 20 mental hospitals in 9 provinces of China from August to November 2020. A self-made questionnaire was used to collect general demographic data. The Functional Assessment of Self-Mutilation, Beck Scale for Suicide Ideation, Kessler Psychological Distress Scale, Stress Mindset Measure-General, Multidimensional Scale of Perceived Social Support, Multidimensional Students' Life Satisfaction Scales, and Rosenberg Self-Esteem Scale were used to collect the information on self-injury behaviors and psychological factors in these adolescents.@*RESULTS@#A total of 529 adolescents with mood disorders and NSSI behaviors were surveyed, among whom 375 were only-child adolescents and 154 were non-only-child adolescents. Compared with the non-only-child group, the only-child group had a significantly higher total score of Functional Assessment of Self-Mutilation (P<0.05) .The type and frequency of self-injury in the only-child group were significantly higher than those in the non-only-child group (P<0.05). Psychological analysis showed that compared with the non-only-child group, the only-child group had a significantly lower score of self-esteem (P<0.05) and significantly higher scores of psychological distress and depressive symptoms (P<0.05). The multiple linear regression analysis showed that the score of suicidal ideation was positively correlated with the frequency of NSSI behaviors in both only-child and non-only-child adolescents with mood disorders (P<0.05); in the only-child adolescents, the level of self-esteem was negatively correlated with the frequency of NSSI behaviors (P<0.05), and the score of stress perception was positively correlated with the frequency of NSSI behaviors (P<0.05); in the non-only-child adolescents, the score of anxious emotion was positively correlated with the frequency of NSSI behaviors (P<0.05).@*CONCLUSIONS@#Among the adolescents with mood disorders and NSSI behaviors, the only-child adolescents tend to have a higher frequency of self-injury and poorer mental health, and therefore, the only-child adolescents with mood disorders and NSSI behaviors need more attention.
Subject(s)
Adolescent , Humans , Cross-Sectional Studies , Mood Disorders , Risk Factors , Self Mutilation , Self-Injurious Behavior/psychology , Suicide, Attempted/psychologyABSTRACT
Objective To investigate the prevalence of Spirometra mansoni infections in hosts in Jiangsu Province, so as to provide the scientific basis for the management of sparganosis mansoni. Methods From 2018 to 2019, nine counties (cities, districts) were randomly selected from Jiangsu Province as the survey sites, and 100 healthy individuals were randomly selected to perform the serological test of S. mansoni infections and the detection of S. mansoni eggs. The procercoids were detected in the intermediate host Cyclops, and the S. mansoni eggs were identified in the stool samples of the definitive hosts cats and dogs. Results The prevalence of S. mansoni human infections was 0 (0/900) in the 9 survey sites of Jiangsu Province, and the sero-prevalence of the specific IgG antibody against S. mansoni was 1.22% (11/900). The positive rate of procercoids was 0.33% (3/900) in Cyclops. In addition, the S. mansoni egg-positive rate was 1.48% (2/135) in cats and dogs. Conclusions Sparganosis mansoni is prevalent in Jiangsu Province. Health education pertaining to the damages of sparganosis mansoni and the route of S. mansoni infections should be improved.
ABSTRACT
Objective:To synthesize a 68Ga-labeled oxalyldiaminopropionic acid (ODAP)-urea based prostate specific membrane antigen (PSMA) targeting probe, and evaluate its properties in vitro and in vivo. Methods:Ligand P151 was synthesized by solid-phase synthesis and its Ki value was determined. The ligand P151 was added into the mixture of 68GaCl 3 and NaOAc solution and was reacted at 95 ℃ for 10 min. The labeling yield and in vitro stability of 68Ga-P151 were determined by high performance liquid chromatography (HPLC). The lipid-water partition coefficient (log P) and cell binding ability were determined. The biodistribution of 68Ga-P151 in normal KM mice was determined. MicroPET imaging of 68Ga-P151 was carried out in prostate cancer 22Rv1 tumor-bearing mice and compared with 68Ga-PSMA 617. Independent sample t test was used to analyze the data. Results:P151 was successfully synthesized with the Ki of 0.58 nmol/L, the labeling yield more than 95% and the radiochemical purity more than 95%. After placement in saline or human serum albumin (HSA) solution at 37 ℃ for 2 h, the radiochemical purity of 68Ga-P151 was still more than 95%, indicating a good stability in vitro. The lipid-water partition coefficient (log P) of 68Ga-P151 was -2.65±0.17, indicating a good hydrophilicity. 68Ga-P151 specifically bound to PSMA in prostate cancer LNCaP cells with the uptake value of (0.83±0.04) percentage injection activity (%IA)/10 5 cells. Biodistribution of normal mice showed that 68Ga-P151 was mainly excreted through kidneys and other organs showed low uptake. MicroPET imaging of tumor-bearing mice showed the maximum standardized uptake value (SUV max: 0.79±0.23 vs 0.54±0.05; t=2.12), tumor/kidney ratio (2.04±0.65 vs 1.88±0.33; t=0.44) and tumor/muscle ratio (12.83±5.18 vs 6.95±1.63; t=2.17) between 68Ga-P151 and 68Ga-PSMA 617 were not significantly different (all P>0.05). Conclusions:68Ga-P151 can be prepared simply and labeled in high yield and show improved pharmacokinetic properties in vivo. The imaging of 68Ga-P151 on PSMA positive tumor is comparable to that of 68Ga-PSMA 617, making it a potential radiopharmaceutical for the diagnosis of prostate cancer.
ABSTRACT
Objective:To investigate the prevalence and influencing factors of amnestic mild cognitive impairment of rural elderly in Guizhou province, which aims to provide scientific basis for the prevention and control of cognitive impairment in the elderly.Methods:Adopting a multi-stage cluster sampling method, a total of 1 535 rural Han and Bouyei elderly people aged 60 and above were selected from Guiyang city and Qiannan prefecture in Guizhou province as the survey subjects for the current situation survey, including demographic sociological characteristics, such as social was utilized behavior, social behavior disease history, height and weight and so on.Mini-mental state examination was utilized to measure cognitive function and SPSS 26.0 statistical software was used to perform χ 2 inspection and multivariate unconditional Logistics regression analysis to calculate odds ratio ( OR) and 95% confidence interval (95% CI). Results:A total of 242 elderly patients with aMCI were detected (15.8%). The results of univariate analysis showed that ethnicity(χ 2=4.333, P<0.05), gender(χ 2=18.367, P<0.01), marital status(χ 2=9.721, P<0.01), occupation(χ 2=7.786, P<0.01), annual family income(χ 2=28.085, P<0.01), current smoking(χ 2=11.873, P<0.01), specific hobbies(χ 2=25.968, P<0.01), physical exercise(χ 2=11.871, P<0.01), living style(χ 2=13.190, P<0.01), and activity participation(χ 2=13.004, P<0.01) all had an impact on aMCI. Multivariate Logistic regression analysis showed that Bouyei nationality( P<0.05, β=0.288, OR=1.333, 95% CI=1.002-1.775) and the women( P<0.05, β=0.516, OR=1.676, 95% CI=1.233-2.278)were risk factors for aMCI, and high annual family income( P<0.05, β=-0.839, OR=0.432, 95% CI=0.308-0.606), specific hobbies( P<0.05, β=-0.580, OR=0.560, 95% CI= 0.394-0.795), physical exercise( P<0.05, β=-0.410, OR=0.664, 95% CI=0.493-0.894), participation in activities( P<0.05, β=-0.424, OR=0.654, 95% CI=0.488-0.877), and non-living alone( P<0.05, β=-0.563, OR=0.569, 95% CI= 0.374-0.866) were the protective factors.Comparison of the prevalence of the disease between the Han and Bouyei nationalities, the detection rate of aMCI for the Bouyei elderly (18.0%) was higher than that of the Han (14.1%) (χ 2=4.333, P<0.05). After stratification according to gender, family annual income, specific hobbies, physical exercise, participation in activities and living style, the detection rate of elderly female subjects of Bouyei nationality was higher than that of Han nationality, whose difference was statistically significant (χ 2=5.562, P<0.05). The detection rate of Bouyei elderly was higher than that of Han when the annual household income was less than 30 000, and the difference was statistically significant (χ 2=8.570, P<0.01). Conclusion:The incidence of aMCI among the elderly of Bouyei nationality is higher, and the incidence of aMCI among females is higher than that of males, which should be paid more attention to.It is of vital importance to strengthen health education and publicity, guide the formation of knowledge-belief-behavior health-related behavior patterns, so as to improve the quality of life and reduce the risk of cognitive impairment.
ABSTRACT
Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
ABSTRACT
OBJECTIVE@#To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI).@*METHODS@#Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg@*RESULTS@#Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL.@*CONCLUSIONS@#TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.
ABSTRACT
Key requirements of successful animal behavior research in the laboratory are robustness, objectivity, and high throughput, which apply to both the recording and analysis of behavior. Many automatic methods of monitoring animal behavior meet these requirements. However, they usually depend on high-performing hardware and sophisticated software, which may be expensive. Here, we describe an automatic infrared behavior-monitor (AIBM) system based on an infrared touchscreen frame. Using this, animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events. This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms. The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient, unbiased, and low-cost manner.
ABSTRACT
Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
ABSTRACT
Objective:To explore the surgical technique and clinical effect of pressure boost in repairing soft tissue defects of limbs with thinned anterolateral thigh perforator flap (ALTP) .Methods:From January, 2015 to December, 2018, 18 cases with soft tissue defects of limbs with various damages of blood vessels and nerves with explosure of tendon and bone. There were 13 males and 5 females aged between 18 to 56 (averaged of 36.3) years, which were 6 defects in shank, 4 in foot and ankle, 5 in forearm, and 3 in hand. The soft tissue defect area was 7 cm ×12 cm to 13 cm ×30 cm. Thinned ALTP was used to repair the wound surface. The perforating vessels of the distal flap were anastomosed with one branch of the internal vessel pedicle flap to increase the pressure hence the blood supply of the distal region. The donor sites were sutured directly or covered by skin graft. Followed-up was conducted by 1-2 monthly clinic visits and telephone or on-line review to check the flap survival and recovery of functions.Results:All flaps survived without arterial or venous crisis. One flap had partial necrosis at the distal end, and healed after dressing change. One case had a swelling flap due to a congestion beneath the flap. The wound achieved primary healing after removal of sutures, ligation of subcutaneous vessels and drainage of hematoma. All patients were followed-up for 6 to 18 (average, 9.5) months. All flaps had good appearance and texture. After rehabilitation treatment, most of the joint activity had been recovered: extension and flexion of wrists joints ranged 60°-80°, 70°-80° for metacarpophalangeal joints and 40°-60° for ankle joints. One patient underwent ankle joint dorsiflexion function reconstruction and flap thinning at 6 months after operation due to the defects of most of the extensor tendon.Conclusion:During the use of free ALTP to repair soft tissue defect of limbs, application of the technique of pressure boost is able to increase blood supply to the distal region of flap. It helps to reduce the incidence of infection and necrosis at the edge of the flap.
ABSTRACT
Objective:To investigate the effects of combined exposure of fluorine, arsenic, and fluorine-arsenic on the signaling pathway related protein expression of tumor necrosis factor receptor-related factor 6 (TRAF-6)/nuclear factor κB1(NF-κB1) in a co-culture system of mouse osteoblasts MC3T3-E1 and mouse monocyte macrophage RAW264.7.Methods:MC3T3-E1 cells were co-cultured with RAW264.7 cells after induction with osteogenic inducers. The cells were cultured for 7 days in vitro, and different doses of sodium fluoride (0.0, 0.1, 0.4, 1.6 mmol/L NaF, F), sodium arsenite (0.0, 0.5, 2.5, 12.5 μmol/L NaAsO 2, As) and different doses of fluorine and arsenic were added to the culture medium and cultured for 24 h using factorial design. The expression levels of nuclear factor κB receptor activating factor (RANK), TRAF-6, NF-κB1, T cell activating factor (NFATc1), and tartrate-resistant acid phosphatase (TRAP) protein were detected by Western blotting. Results:When fluorine was used alone, compared with the control group (F 0.0As 0.0, 1.00 ± 0.00), the expressions of RANK, NF-κB1 and TRAP proteins (1.11 ± 0.04, 1.29 ± 0.05, 1.38 ± 0.04, 1.24 ± 0.04, 1.13 ± 0.03, 1.34 ± 0.05, 1.12 ± 0.03, 1.24 ± 0.04, 1.61 ± 0.06) were increased ( P < 0.05); TRAF-6 protein expressions in F 0.1 and F 1.6 groups (1.23 ± 0.04, 1.35 ± 0.03) were increased ( P < 0.05). When arsenic was used alone, compared with the control group (F 0.0As 0.0), the expressions of RANK, TRAF-6, NF-κB1 proteins were increased in As 0.5 group ( P < 0.05), the expressions of RANK and NFATc1 proteins were reduced in As 12.5 group ( P < 0.05). When fluorine was combined with arsenic, at the same dose of fluorine, RANK protein expression in F 0.1As 0.5 group and TRAF-6 protein expression in F 0.1As 12.5, F 0.4As 0.5, F 0.4As 2.5 groups, NF-κB1 protein expression in F 0.1As 0.5 F 0.4As 2.5, F 0.4As 12.5 groups, NFATc1 protein expression in F 0.1As 0.5 and F 0.4As 0.5 groups, TRAP protein expression in F 0.1As 12.5 group were higher than the corresponding fluorine groups alone (F 0.1, F 0.4, P < 0.05), but lower than the sum of fluorine and arsenic alone. At the same dose of arsenic, RANK protein expression in F 0.1As 12.5 group, TRAF-6 protein expression in F 0.1As 12.5 and F 0.4As 2.5 groups, and NF-κB1 protein expression in F 0.1As 12.5, F 0.4As 2.5, F 0.4As 12.5, and F 1.6As 2.5 groups, TRAP protein expression in F 1.6As 2.5 and F 1.6As 12.5 groups were higher than the corresponding arsenic groups alone (As 2.5, As 12.5, P < 0.05), but lower than the sum of fluorine and arsenic alone. Fluorine had a major effect on the expressions of RANK, TRAF-6, NF-κB1, NFATc1, and TRAP proteins ( F=3.41, 341.73, 66.01, 56.49, 147.40, P < 0.05); arsenic also had a main effect on all protein indicators ( F=686.71, 174.96, 107.32, 235.80, 331.37, P < 0.05); the combined effect of fluorine and arsenic had an interaction effect on each protein indicator ( F=50.39, 234.94, 116.72, 67.77, 36.56, P < 0.05). Conclusions:In the co-culture system of MC3T3-E1 and RAW264.7 cells, fluorine can activate TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins, thereby promoting osteoclast differentiation; the effects of arsenic on the expression of related proteins are not completely consistent. The interaction of fluorine and arsenic exposure on TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins is mainly antagonistic.
ABSTRACT
Objective To investigate the value of 68Ga-prostate specific membrane antigen (PSMA)-617 PET/CT in predicting high-risk prostate cancer.Methods From May 2016 to January 2017,30 patients (median age 67 years) with biopsy-proven prostate cancer were included.The 68Ga-PSMA-617 PET/CT images and clinical data of all patients were analyzed retrospectively.According to prostate cancer risk stratification criteria of National Comprehensive Cancer Network (NCCN) Guidelines (including Gleason scores,prostate specific antigen (PSA)),all patients were classified into low-moderate-risk group and high-riak group.PET images were analyzed semi-quantitatively and maximum standardized uptake value (SUVmax) of primary prostate cancer was measured.SUVmax of 68Ga-PSMA-617 PET/CT was used to establish logistic regression model for predicting high-risk prostate cancer,and the diagnostic efficiency of the model was evaluated by receiver operating characteristic (ROC) curve analysis.Results The median Gleason score of 30 patients was 7.5 (7,9),and the median PSA was 34.0 (19.4,119.1) μg/L,including 9 patients with PSA≤ 20 μg/L and 21 patients with PSA＞20 μg/L.According to the NCCN Guidelines,there were 24 patients with high-risk prostate cancer and 6 patients with low-moderate-risk prostate cancer.SUVmax was higher in high-risk group than that in low-moderate-risk group (14.2 (11.4,23.1) vs 7.9 (3.8,13.1);u =118,P＜ 0.05).Logistic regression model established with SUVmax could effectively predict high-risk prostate cancer with the area under ROC curve of 0.819.When the cut-off value was set as 0.73,the sensitivity and specificity of the model were 87.5％(21/24) and 4/6 respectively.Conclusion SUVmax of 68Ga-PSMA-617 PET/CT can be used as an imaging biomarker for predicting high-risk prostate cancer.