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Objective@#To investigate the incidence of road traffic injuries among online deliverymen and its influencing factors, so as to provide insights into prevention of road traffic injuries.@*Methods@#Online deliverymen who were registered on a takeaway platform and delivered within Baotou City, Inner Mongolia Autonomous Region were recruited using a convenience sampling method, and demographic information, delivery work conditions and road traffic injury data were collected through questionnaire surveys from June to September, 2023. Factors affecting the incidence of road traffic injuries were identified by a multivariable logistic regression model.@*Results@#A total of 603 questionnaires were allocated, and 584 were valid, with an effective rate of 96.85%. There were 467 men (79.97%) and 117 women (20.03%), 200 participants at ages of 31-40 years (34.25%), 215 crowdsourcing deliverymen (36.82%) and 510 full-time (87.33%). The incidence of road traffic injuries in the past one year was 14.90%, and 59 injuries were mild (67.82%). The parts of injuries were mainly upper limbs (31.03%) and lower limbs (45.98%). Multivariable logistic regression analysis showed that online deliverymen who did not wear a helmet at work (OR=2.591, 95%CI: 1.354-4.958) and worked as a crowdsourcing deliverymen (OR=2.232, 95%CI: 1.041-4.786) had higher risks of road traffic injuries, while online deliverymen who worked part-time (OR=0.154, 95%CI: 0.034-0.706) had lower risks of road traffic injuries.@*Conclusions@#The incidence of road traffic injuries among online deliverymen is associated with post, type of work and wearing helmets or not. The traffic safety education and management should be strengthened among online deliverymen.
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Objective@#To learn anxiety, depression, sleep quality and quality of life among patients with primary pruritus ani, and to analyze their correlation with anal itching symptom, so as to provide insights into the prevention and treatment of primary pruritus ani.@*Methods@#Patients with primary pruritus ani were selected from anorectal department of the First Affiliated Hospital of Zhejiang Chinese Medical University. The Visual Analogue Scale, pruritus frequency score, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index and Dermatology Life Quality Index (Chinese version) were used in the survey. Spearman rank correlation analysis was employed to analyze the correlation between the degree and frequency of pruritus ani with, anxiety, depression, sleep quality and quality of life.@*Results@#Sixty patients with primary pruritus ani were investigated, including of 7 males and 53 females, with an average age of (34.37±10.30) years. The patients with mild, moderate and severe pruritus accounted for 28.33%, 48.33% and 23.34%, respectively. The patients with pruritus frequency of grade 1, 2 and 3 accounted for 51.67%, 38.33% and 10.00%, respectively. The patients with anxiety, depression, and coexistence of anxiety and depression accounted for 18.33%, 13.33% and 10.00%, respectively. The patients with very good, good, average and poor sleep quality accounted for 15.00%, 46.66%, 30.00% and 8.34%, respectively. No, mild, moderate and severe impacts on quality of life among the patients accounted for 10.00%, 46.66%, 33.34% and 10.00%, respectively. The degree of pruritus was positively correlated with anxiety (rs=0.405, P=0.001), depression (rs=0.343, P=0.007), sleep quality (rs=0.293, P=0.037) and quality of life (rs=0.338, P=0.008). However, there was no significant correlation between the frequency of pruritus with the above factors (all P>0.05).@*Conclusion@#The degree of pruritus in patients with primary pruritus ani is related to anxiety, depression, sleep quality and quality of life.
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Abstract Objectives To investigate the impact of Three-Dimensional (3D) laparoscopy compared to traditional laparotomy on serum tumor markers and coagulation function in patients diagnosed with early-stage Endometrial Cancer (EC). Method The authors retrospectively analyzed the clinical data of 75 patients diagnosed with early-stage EC and categorized them into two groups based on the surgical techniques employed. The 3D group consisted of 36 patients who underwent 3D laparoscopic surgery, while the Laparotomy group comprised 39 patients who underwent traditional laparotomy. The authors then compared the alterations in serum tumor markers and coagulation function between the two groups. Results Postoperatively, serum levels of CA125, CA199, and HE4 were notably reduced in both groups on the third day, with the levels being more diminished in the 3D group than in the Laparotomy Group (p < 0.05). Conversely, FIB levels escalated significantly in both groups on the third-day post-surgery, with a more pronounced increase in the 3D group. Additionally, PT and APTT durations were reduced and were more so in the 3D group than in the laparotomy group (p < 0.05). Conclusions When juxtaposed with traditional laparotomy, 3D laparoscopic surgery for early-stage EC appears to be more efficacious, characterized by reduced complications, and expedited recovery. It can effectively mitigate serum tumor marker levels, attenuate the inflammatory response and damage to immune function, foster urinary function recovery, and enhance the quality of life. However, it exerts a more significant influence on the patient's coagulation parameters, necessitating meticulous prevention and treatment strategies for thromboembolic events in clinical settings.
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Microbial oil has been gaining considerable attention from researchers recently as renewable and ecofriendly oil and its potential as feedstock for food industry and biodiesel industry. In this context, we have earlier demonstrated production of microbial oil and exopolysaccharide (EPS) from the yeast Sporidiobolus pararoseus JD-2. In this study, we explored increasing its production by optimizing the culture condition and nutrition. As expected, culture temperature and dissolved oxygen (DO) are the contributing factors for co-producing microbial oil and EPS, in which 28? and lower quantum (i.e., 30 mL/500 mL) show the best conditions in shake-flasks fermentation. By contrast, the initial pH from 4 to 8 has no obvious effect on producing microbial oil and EPS. In addition, the culture nutrition (i.e., carbon/nitrogen source) were also discussed, and indicating that 20 g/L of corn steep liquor and 60 g/L of glucose are beneficial to produce microbial oil and EPS (i.e., 34.1±1.2 g/L and 11.5±0.2 g/L, respectively). Meanwhile, the residue glucose should be maintained at 20 g/L, in which the highest production of microbial oil and EPS was obtained (i.e., 34.6±1.7 g/L and 11.7±0.8 g/L, respectively). The biomass, microbial oil and EPS were further increased during optimizing the DO level, which reached to 67.8±2.1 g/L, 34.7±0.6 g/L and 11.8±0.5 g/L during maintaining DO level at 20-30%, respectively. The results suggest that appropriate culture condition and nutrition considerably improve the fermentation performance of S. pararoseus JD-2 and significantly increase co-production of microbial oil and EPS (by 11.2 and 8.3%, respectively) compared to the un-optimized fermentation.
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Objective@#To understand parents attitudes towards adolescent sexual education in Baoshan City of Yunnan Province, and to explore the correlation between attitudes and their proactive behavior in adolescent sexual education, so as to provide reference for improving parents initiative in adolescent sexual health education.@*Methods@#From November to December 2022, a stratified random cluster sampling method was used to select 7 389 parents of students from 35 primary, middle, and high schools in Baoshan City of Yunnan Province for a questionnaire survey on adolescent sexual health education in parents schools. Chi-square tests were conducted to compare the attitudes of parents towards sexual health education among different groups and their proactive behavior in providing sexual health education to their children. A multivariate Logistic regression model was used to analyze the correlation between parents attitudes towards sexual education and proactive sexual health education.@*Results@#Totally 43.17% ( 3 190 ) of parents had a more open attitude towards sex education for their children, with parents of girls, parents of elementary school students, mothers, <30 years old, junior high school education, workers, service personnel, married, harmonious relationships with their children and democratic parents had a higher rate of actively providing sex education for their children ( χ 2=4.65, 401.92, 23.53 , 197.50, 38.18, 13.65, 6.54, 8.07, 32.17, 96.58, P <0.05). Parents with a more conservative attitude towards sex education and parents of boys were negatively correlated with parents actively providing adolescent sexual health education to their children ( OR =0.86, 0.38, P <0.05). Parents who were <30, 30-<40, 40-50 years old, individuals/businesses, married, divorced, had a good and decent relationship with their children were positively correlated with their parents proactive adolescent sexual health education for their children ( OR =1.50, 1.90, 1.37, 1.22, 1.60, 1.32, 1.94, 1.53, P <0.05).@*Conclusion@#A more open attitude towards adolescent sexual health education can serve as a predictive factor for proactive adolescent sexual health education. In order to increase the rate of family sexual health education, it is recommended to enhance parents awareness of their responsibility for their children s sexual health education, promote harmonious parent-child relationships between parents and children, and communicate with their children with an open attitude.
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@#Diabetes mellitus can increase the risk and severity of periodontitis and may be associated with changes in the immune characteristics of periodontal tissues. In this paper, the morphological and immune characteristics of periodontal tissues in diabetic patients were reviewed in terms of the changes of morphology, structure and local immune cells in periodontal tissues caused by hyperglycemia and their regulatory mechanisms.
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@#[Abstract] Objective:To investigate the expression of ITGB2 (integrinβ2) in renal cell carcinoma (RCC) tissues and cells (ACHN cells) and its effects on the proliferation, migration, invasion and cell cycle of ACHN cells. Methods: The expression level of ITGB2 in RCC tissues and para-cancerous tissues was analyzed by GEPIA database. The tissue samples of 66 RCC patients retained in the biological specimen bank of the Fourth Hospital of Hebei Medical University from 2016 to 2020 were selected for this study. The expression level of ITGB2 in 66 cases of RCC tissues and para-cancerous tissues was detected by immunohistochemical SP and qPCR, and the relationship between ITGB2 and clinical parameters was analyzed. The shRNA with ITGB2 knockdown was constructed and transfected into ACHN cells for functional experiments to detect its effect on the malignant biological behaviors of ACHN cells, and its effect on the cell cycle was detected by flow cytometry. WB was used to detect the effect of ITGB2 knockdown on ITGB2 protein expression in ACHN cells. Results: The relative expression of ITGB2 in RCC tissues was significantly higher than that in para-cancerous tissue (P<0.01), and the expression was related to the clinical stage of RCC (P<0.05). Transfection of shITGB2 into ACHN cells could knock down the gene and protein expression of ITGB2 (all P<0.01). Knockdown of ITGB2 could significantly inhibit the proliferation (P<0.05), migration(P<0.01) and invasion (P<0.05) of ACHN cells but had no significant effect on cell cycle (P>0.05). Conclusion: ITGB2 is highly expressed in RCC tissues and cells and is associated with the clinical stage of RCC. Knockdown of ITGB2 can inhibit the malignant biological behaviors of ACHN cells.
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Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias%ranged from-12.2%to-5.2%,precision ranged from-12.4%to-1.4%,and the relative standard deviation(RSD)was less than 6.6%and 8.7%,respectively.The total error was less than 20.4%.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.
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Abstract Objective: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. Method: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. Results: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. Conclusion: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.
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Purpose: To explore the potential immunomodulatory effects of total extract and different polar parts from Blaps rynchopetera Fairmaire. Methods: Phagocytic activity was evaluated by neutral red assay, and the effect of the immune function was investigated by normal and immunocompromised mice models. Results: In vitro, total extract, as well as chloroform, ethyl acetate, n-butanol and water fractions could individually enhance the phagocytic ability of mouse peritoneal macrophages; in addition, chloroform and ethyl acetate fractions had an increasing tendency when combined stimulation with lipopolysaccharide (LPS). In vivo, ethyl acetate fraction (EAF) could enhance the immune organ index, increase the serum hemolysin level and peripheral blood immune cells of immunocompromised mice, while for normal mice, the effect was inconspicuous. Conclusions: Blaps rynchopetera extracts had noteworthy immunomodulatory effect, especially for individuals with immune disorders.
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Animales , Ratones , Escarabajos/química , Huésped Inmunocomprometido , Factores Inmunológicos/análisis , Medicina Tradicional China/métodos , MacrófagosRESUMEN
From providing funds for the global fight against infectious diseases,to actively participating in global health security actions,to strengthening mutual cooperation in the field of health,and providing medical treatment,training and scholarships to countries in need,China's foreign aid on global poverty alleviation is increasingly diversified and expanding in scale.Indeed,China is playing an increasingly important leading role in the global health agenda.It is worth mentioning that over the years,artemisinin compound have saved millions of lives all over the world,especially in poverty-stricken areas.China's work mode of malaria elimination has also been written into WHO's technical documents and recommended to other countries.Since 2007,Chinese medical staff has carried out the Artemisinin Compound Malaria Control Project in Comoros,bringing Chinese prevention and treatment programs to the local area.By 2014,Comoros had achieved zero deaths from malaria,and the number of cases had dropped by 98%.Now,this program is also extended to Togo,another African country.This article preliminarily summarizes the malaria profile in Togo and introduces China-Togo Cooperative Artemisinin Malaria Control Demonstration Project to provide a reference for better anti-malaria assistance in Togo,and also shows one of the substantive actions of China's participation in global health governance,which contributes Chinese wisdom and offers Chinese solutions to global poverty alleviation.
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OBJECTIVES: To investigate the clinical utility of serum microRNA levels (miR-9-5p and miR-128-3p) in the diagnosis and prognosis of early-stage acute ischemic stroke (AIS). METHODS: We compared the differences in serum miR-9-5p and miR-128-3p levels between patients with AIS and healthy individuals (controls). The serum levels of miR-9-5p and miR-128-3p were quantified using quantitative real-time PCR, and the association of each miRNA with AIS was determined using receiver operator characteristic curve analysis. The predictive value of these indices in the diagnosis of early-stage AIS was evaluated in conjunction with that of computed tomography findings and neuron-specific enolase levels. The prognosis of patients with AIS was evaluated three months after their discharge from hospital using the modified Rankin scale, which classifies the prognosis as either favorable or poor. Logistic regression analysis was used to analyze the correlation between miR-9-5p and miR-128-3p levels and patient prognosis. RESULTS: The serum levels of miR-9-5p and miR-128-3p were upregulated in patients with AIS relative to those in healthy individuals. A pronounced correlation was identified between serum miR-9-5p and miR-128-3p levels and patient prognosis, with high levels of both miRNAs being associated with poor patient outcomes. CONCLUSION: Assessment of serum miR-9-5p and miR-128-3p levels is important for the early diagnosis and prognosis of AIS.
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Humanos , Isquemia Encefálica/diagnóstico , MicroARNs/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Curva ROCRESUMEN
Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.
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Humanos , Malaria Falciparum/tratamiento farmacológico , Artemisininas/efectos adversos , Malaria/tratamiento farmacológico , Antimaláricos/efectos adversos , Quinolinas , Combinación de Medicamentos , Electrocardiografía , Arteméter/uso terapéutico , Combinación Arteméter y Lumefantrina/uso terapéuticoRESUMEN
@#Clinical trials are the key step in verifying the effectiveness, safety and usability of novel oral medical devices. With improvements in invention capability, the number of clinical trials of medical devices has steadily increased domestically, indicating the need for new requirements for quality management. Here, on the basis of summarizing the characteristics of clinical trials for oral medical devices in China, we proposed a whole-process quality-control model for good clinical practice (WQGCP). This model clarified the management specifications for oral medical device clinical trials in the new era. It indicates that the clinical trial design is the breakthrough point, while whole-process risk control is the key point. This suggests the need for the establishment of a quality management cooperation system, evaluation and postevaluation systems and the training of high-level personnel who conduct clinical trials. It also provides suggestions to promote the participation of oral clinicians in high-quality research and invention of novel clinical medical devices with the aim of accelerating the development of oral medical devices in China.
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@#Objective By summarizing the clinical characteristics of perioperative patients with cross infection of novel coronavirus in thoracic surgery ward, to guide the prevention and treatment of nosocomial infection during the anti-epidemic period. Methods The clinical data of 451 patients with chest diseases in the Department of Thoracic Surgery of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1st to 24th, 2020 were analyzed and followed up. There were 245 surgical patients and 206 non-surgical patients. Results In the department, 7 patients (7/451, 1.55%) were infected with the novel coronavirus and all of them were surgical patients, whose preoperative imaging data did not reveal the imaging changes of novel coronavirus. There were 5 males and 2 females, aged 56 to 68 years. The patients with old age, smoking, surgery, coronary heart disease, chronic liver disease and tumor history were more susceptible to infection. From the spatial distribution of patient beds, it was found that the distance among infected patients was greater than 1 m, and no cross infection was found in the other patients of the same ward. During follow-up, two family members of noninfected patients were found to be infected one week after discharge. However, there was no overlap of spatiotemporal distribution between the family members and the infected patients during the hospitalization period. Conclusion The novel coronavirus pneumonia rate in the department of thoracic surgery is low, which may be opportunistic infection. At the same time, a good control and prevention of epidemic disease can reduce the occurrence of cross infection in the department of thoracic surgery.
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@#[Abstract] Objective: To investigate the expression of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) in breast cancer tissues and its correlation with clinicopathological features and prognosis of patients. Methods:Atotal of 136 breast cancer tissue chips (purchased from Superchip Company), including 42 pairs of matched cancer and paracancerous tissues, were used for this study. The expression level of CMTM6 in cancer and paracancerous tissues was detected by immunohistochemistry. The comparison of CMTM6 expression between breast cancer and paracancerous tissues was conducted by paired χ2 test. The relationship between CMTM6 expression in breast cancer tissues and the clinicopathological characteristics of patients was analyzed by χ2 test. Kaplan-Meier and Log rank test analyses were used to analyze the relationship between CMTM6 expression and the survival of patients, and Cox model was used to evaluate the effect of different indicators on the prognosis of patients. Results: The expression of CMTM6 in breast cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The expression of CMTM6 was correlated with pathological type of breast cancer and HER2 positivity (P<0.05). The survival time of patients in CMTM6 high expression group was significantly shorter than that of patients in CMTM6 low expression group (P<0.05). Pathological type (HR=10.374, 95%CI: 3.529-30.497, P<0.01), TNM stage (HR=4.599, 95%CI: 1.784-11.856, P<0.01), triple-negative breast cancer (HR=3.370, 95%CI: 1.055-10.761, P<0.05) and high expression of CMTM6 (HR=0.195, 95%CI: 0.073-0.518, P<0.01) were independent risk factors for prognosis of breast cancer patients. Conclusion: CMTM6 is highly expressed in breast cancer tissues, which can be used as a risk factor for prognosis evaluation of breast cancer patients.
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Objective@#To analyze Internet behaviors of children and adolescents and their influencing factors, and to provide scientific basis for health education guidance and prevention measures.@*Methods@#A stratified cluster sampling method was used. From January to June 2019, 30 955 primary school students in 16 provinces (municipalities), from eastern, central, and western economic zones of China were selected to conduct a questionnaire survey, regarding general demographics, diet and exercise, tobacco, alcohol and sleep, Internet and electronics usage, etc.@*Results@#Among them, 43.1% of students had never been online with girls (44.7%) higher than boys (41.8%)(χ2=21.04, P<0.01); 1.3% of students reported online time for more than 4 hours a day, boys were significantly higher than girls(χ2=15.87, P<0.01); Internet addiction was detected in 2.4% of elementary school students, with boys (3.0%) higher than girls(1.7%)(χ2=331.77, P<0.01), and the trend increases with grade. With sixth grade (3.3%) were significantly higher than children from the first grade (0.8%) and other grades(χ2=163.96, P<0.01). Children’s tendency to Internet addiction was 11.9%, of which boys were 13.0% and girls were 10.6%, boys were significantly higher than girls(χ2=117.66, P<0.01). Pearson correlation analysis revealed that, after controlling gender age, boarding school, family relationship, single parents and regrouped families, smoking, drinking sugary drinks, eating fried foods, and left-behind were positively related to Intenet addiction(r=0.06, 0.07, 0.27, 0.44, 0.07, 0.11, 0.09, P<0.01), while medium and high intensity sports, effective physical education, health education in school, AIDS education and parental restrictions on TV and computer games, were negatively associated with internet addiction(r=-0.74, -0.65, -0.04, -0.05, -0.63, P<0.01).@*Conclusion@#The internet addiction of Chinese primary school students is common and increases by year. High-intensity, high-density sports, effective physical education, and health education could help prevent Internet addiction among children.
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BACKGROUND: Studies have shown that mesenchymal stem cells can reduce inflammation, promote wound healing, and reduce scar formation in wound healing. However, previous two-dimensional culture environment can lead to differences in gene expression, signal transduction, and morphology because of intracellular contact inhibition. OBJECTIVE: To investigate whether the ability of wound healing related factors secreted by human amniotic mesenchymal stem cells is affected by two-dimensional or three-dimensional culture environment. METHODS: The human amniotic mesenchymal stem cells cultured by traditional enzyme digestion method were inoculated in traditional cell culture flask (two-dimensional culture group) and ShakeGelTM 3D hydrogel (three-dimensional culture group) and induced to differentiate into adipocytes, osteoblasts, and chondrocytes, respectively. The direction of cell differentiation was determined by immunofluorescence staining. Human amniotic mesenchymal stem cells were fused to 70%-80% in two culture environments, and the growth characteristics and morphology of cells were observed under inverted phase contrast microscope and laser confocal microscope. After 24 hours of culture, relative mRNA expression of wound healing-related factors was detected by reverse transcription-quantitative polymerase chain reaction. After 48 hours of culture, the protein expression of wound healing-related factors was detected by the enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: (1) Human amniotic mesenchymal stem cells cultured in two-dimensional culture group were flat and spindle-shaped, which was a typical mesenchymal stem cell-like morphology. Human amniotic mesenchymal stem cells in the three-dimensional culture group were round and evenly dispersed in each layer of the hydrogel. (2) Human amniotic mesenchymal stem cells in the three-dimensional culture group exhibited the potential to differentiate into adipocytes, osteoblasts, and chondrocytes. (3) The mRNA expression of interleukin-6, interleukin-8, epidermal growth factor, basic fibroblast growth factor, hyaluronic acid, hepatocyte growth factor, and vascular endothelial growth factor in the three-dimensional culture group was significantly higher than that in the two-dimensional culture group (P 0.05). (4) The protein expression of interleukin-6, interleukin-8, interleukin-10, epidermal growth factor, basic fibroblast growth factor, hepatocyte growth factor, transforming growth factor β1 and vascular endothelial growth factor in the three-dimensional culture group was significantly higher than that in the two-dimensional culture (P 0.05). (5) These findings suggest that human amniotic mesenchymal stem cells cultured in three-dimensional hydrogel show better morphology and more encouraging paracrine effect of wound healing related factors than those cultured in traditional two-dimensional culture environment.
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T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers
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Humanos , Masculino , Femenino , Adolescente , Adulto , Seguridad , Voluntarios , Dosis Única/efectos de los fármacos , Etanercept/análogos & derivados , Examen Físico , Artritis Reumatoide/patología , Factor de Necrosis Tumoral alfa/clasificación , Técnicas de Laboratorio Clínico , Pueblo Asiatico/clasificación , Electrocardiografía , Reacción en el Punto de Inyección , Inyecciones Subcutáneas/clasificaciónRESUMEN
Abstract Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.