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During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.
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ObjectiveAutonomic dysfunction is a common and serious complication in patients with early chronic kidney disease (CKD). Sweat gland dysfunction is an initial sign of autonomic dysfunction. Electrochemical skin conductance (ESC) measurement by reverse iontophoresis and chronoamperometry to assess sweat gland function may detect patients with mild renal insufficiency in healthy population for early intervention and treatment to delay further deterioration of renal function. MethodsAn EZSCAN score (0~100) was calculated using a proprietary algorithm based on the chronoamperometry analysis. A total of 6 661 subjects who received physical examination from the physical examination center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to October 2020 were enrolled, including 2 075 (31.15%) subjects with reduced renal function (eGFR < 90 mL·min-1·1.73 m-2) as the case group and 4 586 (68.85%) subjects with normal renal function (90 mL·min-1·1.73 m-2≤ eGFR ≤120 mL·min-1·1.73 m-2) as the control group. Lasso regression was used to screen covariates, and the relationship between the risk score and eGFR was analyzed by loess curve and logistic regression. ResultsAfter multivariate adjustment, the risk score was correlated with the risk of eGFR decline. Compared with the group with the lowest risk value (Q1<24), the OR(95%CI )of Q2 (25-27), Q3 (28-47), and Q4 (48-75) were 1.85 (1.55, 2.21), 2.53 (2.13, 3.00), 2.49 (2.13, 2.93), respectively. The maximum area under the ROC curve is 0.75(0.74,0.76), the sensitivity is 73.98%, the specificity is 63%, the positive predictive value is 47.49%, the negative predictive value is 84.25%, and the Youden index is 0.369 72, the optimal cutoff value is 25. ConclusionsEZSCAN could be a useful screening tool to identify healthy individuals at increased risk of renal function decline, and the one with an EZSCAN score of more than 25% should undergo diagnostic laboratory testing.
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Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.
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A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.
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AIM: To investigate the effect of the intravitreal injection of vascular endothelial growth factor-A165(VEGF-A165)on the scleral remodeling of guinea pigs with form-deprivation myopia(FDM).METHODS: A total of 120 tricolor guinea pigs, aged three weeks, were randomly divided into 6 groups, with 20 in each group. The blank group did not undergo any intervention. In the FDM group, only the FDM model was established. In the phosphate buffer saline(PBS)group, 2.5 μL of PBS was injected into the vitreous cavity before establishing the FDM model. In the 1ng group, 5ng group, and 10ng group, VEGF-A165 was injected into the vitreous cavity at concentrations of 1, 5 and 10ng, respectively, before the establishment of the FDM model. The FDM model was established by covering the right eyes of guinea pigs with translucent balloons for 14d. The diopter and axial length of the right eyes were measured before and after covering. After 14d, the content of dopamine(DA)in retina was measured by high performance liquid chromatography. Additionally, the mRNA and protein expression levels of matrix metalloproteinase-2(MMP-2), tissue inhibitor of matrix metalloproteinase-2(TIMP-2), transforming growth factor(TGF)-β1, TGF-β2 and α-smooth muscle actin(α-SMA)in sclera were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.RESULTS: Before covering, there were no significant differences in the diopter and axial length of the right eyes of guinea pigs in all groups(P>0.05). After 14d of modeling, when compared with the blank group, FDM group showed an increase in the degree of myopia in the right eye, a prolongation of the axial length, a decrease in the content of DA in the retina, and an increase in the expression of MMP-2, TGF-β2 and α-SMA in the sclera. Conversely, the expression of TIMP-2 and TGF-β1 were decreased(P<0.01). However, in comparison to the FDM group, the degree of myopia in the 1ng, 5ng, and 10ng groups of guinea pigs decreased, the growth trend of axial length slowed, the content of DA in the retina increased, and the expression of MMP-2, TGF-β2 and α-SMA in the sclera decreased. Furthermore, the expression of TIMP-2 and TGF-β1 in the sclera increased(P<0.01). As the concentration of intravitreal injection of VEGF-A165 increased, the degree of myopia in the right eye of guinea pigs gradually increased, and the axial length gradually prolonged. The content of DA in the retina gradually decreased, the expression of MMP-2, TGF-β2, and α-SMA in the sclera gradually increased, while the expression of TIMP-2 and TGF-β1 decreased gradually.CONCLUSION: Intravitreal injection of VEGF-A165 can increase the content of DA in the retina of FDM guinea pigs, affect the expression of MMP-2, TIMP-2, TGF-β1, TGF-β2 and α-SMA in the sclera, and inhibit scleral remodeling of guinea pigs. Notably, the VEGF-A165 at the concentration of 1ng showed the most significant efficacy.
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Objective:To study influencing factors of prognosis of patients with atrial fibrillation(AF)and heart fail-ure(HF)after rhythm control therapy.Methods:According to rhythm control methods,a total of 379 AF+HF patients treated in our hospital were divided into medication group(n=133)and surgery group(n=246,received catheter ablation of AF);according to AF type,patients were divided into paroxysmal AF group(n=208)and per-sistent AF group(n=171),and general clinical data and rhythm control effect were compared among all groups.According to NYHA cardiac function classification,patients were divided into NYHA classⅡ group(n=160),classⅢ group(n=188)and class Ⅳ group(n=31),and rhythm control effect was compared among above groups.Re-sults:Compared with medication,there were significant reductions in percentage of AF recurrence and LAD after treatment,and significant rise in percentage of heart function improvement in paroxysmal AF group,persistent AF group,NYHA class Ⅱ and Ⅲ group in those underwent surgery(P<0.05 or<0.01).Multivariate Logistic re-gression analysis indicated that medication,persistent AF were independent risk factors for AF recurrence and no cardiac function improvement after rhythm control therapy(OR=2.426~7.908,P=0.001 all),and NYHA classⅡ was an independent protective factor for AF recurrence after rhythm control therapy(OR=0.393,P=0.049).Conclusion:Atrial fibrillation catheter ablation can significantly improve prognosis of AF+HF patients.Persistent AF and antiarrhythmic medication are independent risk factors for poor prognosis after rhythm control therapy.
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Objective:To explore the differences in clinicopathological features, survival status and prognostic influencing factors of breast cancer patients with different molecular subtypes, and to provide bases for the prevention and treatment of breast cancer.Methods:The clinicopathological data of new-onset female breast cancer patients hospitalized in Shanxi Province Cancer Hospital from January 2015 to December 2016 were retrospectively analyzed, and patients were followed up. The clinicopathological features of patients with different molecular subtypes were compared. The follow-up was performed until June 30, 2021. Kaplan-Meier method was used to analyze the survival of patients, and Cox proportional hazards model was used to analyze the factors affecting overall survival (OS) of patients with different molecular subtypes.Results:There were 272 (14.9%), 1 005 (55.2%), 277 (15.2%) and 268 (14.7%) patients with subtypes of Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer (TNBC), respectively. The differences in the distribution of patients with age at diagnosis, age at menarche, menopausal status, age at menopause, pathological type, longest tumor diameter, T staging, N staging, histological grading, and TNM staging were statistically significant among the four groups (all P < 0.05). At a median follow-up of 60 months, the 5-year OS rates of Luminal A, Luminal B, HER2 overexpression and TNBC subtypes were 93.8%, 89.2%, 77.6% and 78.0%, respectively, and the difference was statistically significant ( χ2 = 58.76, P < 0.001). M staging was an independent influencing factor for OS in patients with Luminal A breast cancer ( HR = 16.789, 95% CI 4.972-56.690, P < 0.001); T staging ( HR = 2.721, 95% CI 1.715-4.319), N staging ( HR = 4.460, 95% CI 2.399-8.291) and M staging ( HR = 3.364, 95% CI 1.988-6.670) were independent influencing factors for OS in patients with Luminal B breast cancer (all P < 0.001); N staging ( HR = 4.428, 95% CI 1.836-10.677) and M staging ( HR = 13.489, 95% CI 6.043-30.107) were independent influencing factors for OS of patients with HER2 overexpression breast cancer (both P < 0.01); T staging ( HR = 3.052, 95% CI 1.575-5.915), N staging ( HR = 2.492, 95% CI 1.298-4.785) and M staging ( HR = 33.012, 95% CI 8.606-126.637) were independent influencing factors for OS of patients with TNBC (all P < 0.01). Conclusions:The clinicopathological features and prognostic influencing factors of breast cancer patients with different molecular subtypes are different, and the prognosis of HER2 overexpression and TNBC patients is poor. Clinicians should provide individualized treatment and follow-up programs for patients with different molecular subtypes of breast cancer.
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Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-
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Aim To clarify the regulatory effect of Artesunate(ART) on tumor cell function and cell cycle in the pathological process of esophageal squamous cell carcinoma(ESCC). Methods KYSE450 and TE14 cells were treated with different concentrations of ART. The cells treated with 0 mg •L
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AIM: To investigate the correlation between 25-hydroxyvitamin D and metabolically associated fatty liver disease in type 2 diabetes mellitus. METHODS: A total of 2 406 subjects in Standardized Metabolic Disease Control were recruited from the National Center for Standardized Metabolic Disease Control in The First Hospital of Lanzhou University. The population was divided into Q1, Q2, Q3 and Q4 according to 25(OH)D quartile. The prevalence of MAFLD and related clinical indicators among the four groups were compared, and the influencing factors of MAFLD were analyzed by Logistic regression. Restricted cubic spline (RCS) was used to explore the relationship between 25(OH)D and MAFLD. RESULTS: The prevalence of MAFLD was different with different vitamin D levels. The prevalence of MAFLD was lower in the group with high 25(OH)D level. The level of 25(OH)D in patients with MAFLD was lower than that in patients with T2DM alone, and the number of vitamin D deficiency was relatively higher. Multivariate regression analysis showed that 25(OH)D was not associated with the risk of MAFLD. RCS analysis also suggested that 25(OH)D was not associated with the risk of MAFLD. CONCLUSION: The prevalence of MAFLD is high in people with low vitamin D level, and vitamin D is not associated with the risk of MAFLD after multivariate adjustment.
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Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O
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This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.
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Ratas , Animales , Ratas Sprague-Dawley , Depresión/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/metabolismo , Proteómica , Hipocampo , Estrés Psicológico/metabolismo , Esfingolípidos/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios ChinosRESUMEN
Objective:To investigate the level of self-compassion among residents and related influencing factors, and to help them improve self-compassion ability, achieve learning goals, and increase the degree of satisfaction with learning.Methods:In July 2022, the random sampling method was used to select 330 residents (postgraduate students majoring in clinical medicine after national unified recruitment) from two grade A tertiary hospitals in Shenyang of Liaoning province in China, and Self-Compassion Scale was used for investigation. SPSS software was used to analyze the degree of satisfaction with industry, learning pressure, the balance between learning and life, and occupational burnout among residents and their association with the level of self-compassion through the chi-square test, the one-way analysis of variance, and the multilevel regression analysis.Results:The residents had a mean self-compassion score of (40.90±6.81), and the residents of the second grade had a lower level of self-compassion than those of the other grades. Major satisfaction and balance between learning and life were positively correlated with self-compassion, and occupational burnout was negatively correlated with self-compassion.Conclusion:There is a relatively insufficient level of self-compassion among residents, and improving self-compassion level may effectively regulate occupational burnout, professional satisfaction, and the balance between learning and life, thereby helping to improve learning and mental health.
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Objective:To analyze the mutation types and distribution characteristics of thalassemia gene among high-risk populations in Sanya City, and to evaluate the effectiveness of blood routine screening, in order to provide scientific basis for formulating measures for prevention and control of thalassemia in Sanya City.Methods:Retrospective analysis was used to collect detection results and clinical data from high-risk individuals who completed genetic screening for thalassemia at Sanya Materal and Child Health Hospital from January 2019 to August 2021. Mutation types and distribution characteristics of thalassemia gene were analyzed, and the missed detection rate and sensitivity of blood routine indicators [mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH)] were evaluated based on the results of genetic screening for thalassemia.Results:A total of 5 760 high-risk individuals were included in the screening results of thalassemia genes, and 3 868 samples of thalassemia gene mutations were detected, with a detection rate of 67.15%. Among them, there were 2 979 samples with α-thalassemia genetic mutations, with a detection rate of 51.72%; including 2 966 common genotype samples (99.56%), the main genotype was αα/-α 3.7 (20.14%, 600/2 979); 13 rare genotype samples (0.44%), 4 cases of αα/-- THAI, 3 cases of α CD40(AAG>AA-)α/αα, 2 cases of α PPα/αα, and 1 case of Fusion gene/αα, Fusion gene/α WSα, α WSα/α PPα, and α CD40(AAG>AA-)α/α WSα each. There were 340 samples with β-thalassemia gene mutations, with a detection rate of 5.90%; including 336 common genotype samples (98.82%). The β CD41/42/β N genotype was dominant (57.65%, 196/340); 4 rare genotype samples (1.18%), β CD5(-CT)/β N, β IVS-Ⅱ-2(-T)/β N, β IVS-Ⅱ-761(-T)/β N and β Initiation(ATG>AGG)/β N 1 case each. There were 549 samples of αβ-compound type thalassemia, with a detection rate of 9.53%. The α missing recombination β CD41/42 genotype was dominant (61.02%, 335/549). There were a total of 4 226 samples that could be traced back to MCV and MCH. Among them, 3 007 samples were found to have mutations in thalassemia genes through screening, 2 584 cases were found to have abnormalities in the combination of MCV and MCH indicators, and 423 samples were missed in blood routine screening, with a missed detection rate of 14.07% (423/3 007). The missed samples were mainly α static type, accounting for 89.13% (377/423) of the total missed samples. The screening sensitivity of MCV combined with MCH for α-, β- and αβ-compound type thalassemia was 82.65%, 98.07% and 98.15%, respectively. Conclusion:The types of genetic mutations in thalassemia in Sanya City are complex and diverse, and there are certain omissions in the blood routine screening of MCV combined with MCH.
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This study explored three molecular typing methods for Vibrio parahaemolyticus(VP)in Liaoning Province in 2020,to assess the correlation among the three methods and the genetic relationships among between strains;analyze the epi-demic trends and distribution patterns of VPin Liaoning Province;and provide reliable technical support for the prevention and control of foodborne diseases.Serum typing,PFGE,REP-PCR,and ERIC-PCR molecular typing and cluster analysis were performed on 44 VP isolates from Liaoning Province in 2020.A total of 44 isolated strains were divided into 15 serotypes,and 8 isolated strains could not be classified.The serotypes were primarily O3 group,O1 group,and O2 group.Clinical isolates had high molecular similarity,whereas food isolates had low molecular similarity.The resolution(DI)of PFGE was 0.986,that of REP-PCR was 0.947,and that of ERIC-PCR was 0.935.The molecular similarity between serotype O3 and O1 group strains was high.The epidemic serotypes of isolated VP strains in Liaoning Province in 2020 were consistent with those from the past 5 years.The resolution of the PFGE typing method was better than that of REP-PCR and ERIC-PCR;moreover,REP-PCR had better resolution than ERIC-PCR.These three typing methods showed good intercorrelation.The O3 group strains are likely to originate from the O1 group strains.When a foodborne disease outbreak is caused by VP,laboratories with conditions can apply these three methods to trace the source of the pathogenic bacteriaquickly and effectively.
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Objective@#Based on physical activity (PA) and sedentary behavior (SB) variables on weekdays and weekends, the study aims to cluster the physical activities inside and outside kindergartens and to explore the cluster characteristics of different children using physical fitness indicators, so as to provide new strategies and methods for early childhood education and health.@*Methods@#From March to June 2019, 291 children aged 3-6 years from 6 kindergartens in Nanchang were recruited by a stratified cluster random sampling method. The ActiGraph GT3X-BT triaxial accelerometer was used to measure and analyze the PA and SB levels inside and outside the kindergarten. A twostep clustering algorithm model was employed for cluster analysis. Physical fitness were measured and evaluated according to the "National Physical Fitness Measurement Standard Manual (Preschool Section)". Differences in physical fitness among different clusters of children were compared, and the cluster characteristics of different children were analyzed.@*Results@#The clustering algorithm model indicated that based on six indicators, including PA and SB inside the kindergarten on weekdays, and PA and SB outside the kindergarten on both weekdays and weekends, children could be divided into three categories:active inside (high PA, low SB inside), active outside (high PA outside), and inactive (low PA, high SB both inside and outside). The average silhouette coefficient of the model was 0.3, indicating good clustering results. Both the active inside and active outside children showed significantly higher PA inside on weekdays, PA outside on weekdays and weekends, daily low intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) than the inactive children ( F=157.91, 80.79 , 95.86, 95.52, 124.74, P <0.05). After adjusting for gender and age, the physical fitness scores of both active outside ( 19.03 ±0.47) and active inside (19.11±0.40) were significantly higher than those of the inactive children (17.94±0.31). Additionally, active inside children (3.91±0.14) also showed significantly better performance in continuous double-leg jumps, compared to inactive children (3.45±0.11) ( P <0.05).@*Conclusion@#Children active inside and those active outside perform well in PA. Future research should focus on the proportion of structured and unstructured PA time to enhance the overall physical fitness of children.
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Electronic sports (E-sports) are series of competitive activities different from the traditional physical sports, and E-sports athlete is becoming a new profession. Along with the fast development of E-sports industry, the number of E-sports athletes increased tremendously. The early retirement of some top-ranking athletes caused by occupational injuries has aroused the societal attentions on the health problems of E-sports athletes. Facing special occupational exposure, E-sports athletes encounter different health issues comparing to the counterparts of their ages. It is necessary to scientifically identify their health hazards and common health issues, in order to conduct effective health management for this particular professional group. This review summarized global literature on health issues and health management on E-sports athletes. The research on their health issues were mainly descriptive and there was a paucity on interventional research and health management. These provide references and directions on the future health services and research on E-sports athletes.
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Humanos , Atletas , Traumatismos en Atletas/prevención & control , Electrónica , Traumatismos Ocupacionales , DeportesRESUMEN
OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.
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Animales , Ratones , Ácido Aspártico/metabolismo , Corteza Cerebral , Espinas Dendríticas/metabolismo , Neuronas/metabolismo , Sinapsis , Triptófano/metabolismoRESUMEN
OBJECTIVE@#To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC).@*METHODS@#We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments.@*RESULTS@#MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05).@*CONCLUSION@#MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.
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Humanos , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Ciclina D1/genética , Neoplasias Renales/metabolismo , MicroARNs/metabolismoRESUMEN
OBJECTIVES@#To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring.@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD.@*RESULTS@#The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05).@*CONCLUSIONS@#Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.