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ObjectiveTo investigate the current situation of health communication carried out by medical institutions in Shanghai through new media platforms such as WeChat, Weibo, Toutiao, Douyin, Kuaishou, Bilibili and WeChat Videos, and to propose targeted measures. MethodsBased on the systematic collection of new media accounts of medical institutions in Shanghai, and through the combination of keyword screening and manual audit, health communication data of medical institutions on new media platforms were determined. ResultsData from 1 117 new media accounts of 162 medical institutions in Shanghai were collected, including 610 WeChat official accounts, 105 WeChat video accounts, 89 Weibo accounts, 18 Bilibili accounts, 198 Douyin accounts, 37 Toutiao accounts, and 60 Kuaishou accounts, totaling 111 853 posts. After keyword sorting and manual screening, a total of 66 761 health science posts were collected, with WeChat Official Accounts, Douyin, and Weibo having the top three highest number of posts. Video-based new media such as Douyin, WeChat Videos, Kuaishou, and Bilibili had a better communication impact than text and image-based new media like WeChat Official Accounts, Weibo, and Toutiao. Among them, Douyin and Toutiao were the best platforms for video and text-image-based new media, respectively. ConclusionMedical institutions in Shanghai recognize the importance of new media in health communication and have made full use of various media platforms to carry out health communication,having a certain impact on health education. In the future, medical institutions should choose appropriate platforms based on target audiences and content characteristics, fully leverage the advantages of various platforms, explore innovative communication strategies, promote the dissemination of health knowledge, and enhance the health literacy of the public.
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In recent years, the incidence of cerebral small vessel disease (CSVD) has been increasing with the aging of the population, and the cognitive impairment caused by it has brought huge burden to patients and their families. As a novel inflammatory biomarker, lipoprotein-associated phospholipase A 2 (Lp-PLA 2) directly participates in the pathogenesis of cognitive impairment in patients with CSVD by regulating circulatory vascular injury and neuroinflammation, and is expected to become a predictive indicator and therapeutic target for CSVD.
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Objective:To construct a representative index system for evaluating pediatric orthopedic nursing quality, providing a basis for hospital pediatric orthopedic nursing quality assessment and monitoring.Methods:From April to July 2023, using the "structure-process-outcome" three-dimensional quality structure model as the theoretical framework, a literature review was conducted, and an item pool was formulated. Through two rounds of Delphi method expert consultations, the hierarchical analysis method was finally employed to determine the indicators and their weights at each level.Results:The effective recovery rates of the questionnaire of the two rounds of expert consultations were 100% (20/20), the authority coefficients of experts were 0.87 and 0.88, the coefficients of variation were 0.00 to 0.27 and 0.00 to 0.24. The Kendell harmony coefficients of the second and third indicators in the two rounds of inquiry were 0.140, 0.166 and 0.192, 0.161(all P<0.05). The final pediatric orthopedic nursing quality evaluation index system included 3 primary indicators, 21 secondary indicators and 83 tertiary indicators. Among the primary indicators, the weight of process quality was the highest at 0.493 4, followed by outcome quality at 0.310 8, and the lowest was structural quality at 0.195 8. In the secondary indicators, "assessment criteria of limb blood circulation" had the highest weight at 0.099 8. Conclusions:The constructed pediatric orthopedic nursing quality evaluation index system covers key aspects and is more operationally feasible. It provides better guidance for nursing interventions and quality control.
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Objective To explore the clinical characteristics and liver injury-related risk factors of thyroid-associated ophthalmopathy(TAO)patients with liver function impairment.Methods In this retrospective cohort study,the clinical data of 1 030 TAO patients who visited Henan Provincial People's Hospital from July 2017 to May 2023 was collected.These patients were divided into TAO patients with liver injury(Group A,132 patients)and TAO patients with normal liver func-tion(Group B,898 patients).The age,gender,smoking history,liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl transpeptidase(γ-GT),total bilirubin(TBil),direct bilirubin(DBil),and alkaline phosphatase(ALP)],thyroid function-related indicators[free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),thyrotropin receptor antibody(TRAb),thyroid peroxidase antibody(TPO-Ab),and thyroglobulin antibody],and eye signs[eye protrusion degree,intraocular pressure,absence or occurrence of upper eyelid retraction,NOSPECS grading,clinical activity score(CAS),and number of affected ocular muscles of both eyes]of two groups were collected and compared.Multivariate logistic regression analysis was used to identify the risk fac-tors for liver injury in TAO patients.Results The proportion of liver injury in patients who were initially diagnosed with TAO and received no treatment was 12.82%.There was no statistically significant difference in the gender distribution and the proportion of smokers between the two groups(both P>0.05).The age of patients in Group A[(44.63+13.64)years]was higher than that in Group B[(40.25±14.04)years],and the difference was statistically significant(t=3.718,P<0.05).The levels of ALT,AST,γ-GT,ALP,TBil and DBil in Group A were higher than those in Group B,and the differences were statistically significant(allP<0.01).The FT3,FT4,TPOAb and TRAb levels in Group A were higher than those in Group B,while the TSH level was lower than that in Group B(all P<0.01).The number of affected ocular mus-cles of both eyes and the proportion of patients with a CAS score≥3 in Group A were higher than those in Group B(both P<0.05).The regression analysis results showed that the higher the FT4 and TRAb levels,the older the age,and the lower the TSH level,the higher the risk of liver injury in TAO patients.Conclusion High levels of FT4 and TRAb,as well as low TSH level and advanced age,are independent risk factors for liver injury in TAO patients.The direct toxic effects of immune factors and high thyroxine level on the liver are jointly involved in the mechanism of liver injury in TAO patients.
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Objective:To investigate the effect of backfilling on the deformity of lacrimal sulcus and blepharobuccal sulcus after special treatment of the fat from orbital septum of the pouch in the lower intra-palpebral approach.Methods:From November 2019 to September 2022, a total of 42 patients (13 males and 29 females) aged 16-47(23.8±6.9) years with orbital septal fat swelling were treated by the surgical department of Beijing Huangsi Medical Cosmetic Clinic after the removal of orbital fat mass by the intraocular pouch approach. With mild, moderate, and severe lacrimal sulci and blepharobuccal depression deformity, the lower eyelid skin was not relaxed. The naturally herniated orbital septal adipose mass was cut off through the lower eyelid conjunctival incision approach, and then granulated into a 1 ml syringe, which was accurately filled into the depressed area of lacrimal sulci and blepharobuccal sulci according to the depressions marked before surgery.Results:The incisions of all 42 patients healed in the first stage without hematoma and infection, and the subcutaneous ecchymosis of 2 cases was observed by local hot compress 48 h later and the ecchymosis subsided 1 week. Follow-up was performed at 1 month, 2 months and 3 months, respectively. Among them, 35 patients underwent the operation of removing the lower eyelid bag and orbital septum cellulite and backfilling to correct the malformation of lacrimal sulci, and the postoperative effect was satisfactory. The symptoms of puffed eye bags, blepharobuccal sulci and lacrimal sulci depression disappeared, and the wound healed in one stage. 7 patients with eye bags accompanied by lacrimal sulci and blepharobuccal sulci were told before surgery that they might need two fat fillings due to insufficient fat content in the orbital septa and slight indentations. One month later, granular fat was taken from the legs to fill the lacrimal sulci and blepharobuccal sulci with satisfactory results.Conclusions:The treatment after the removal of orbital septum cellulite and the correction of lacrimal sulcus and blepharobuccal sulcus deformity are simple and satisfactory, and worthy of clinical application.
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Abstract Background The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. Objective and limitations of the study The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. Methods A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. Results Lower levels of serum GLA in rosacea patients were observed (p < 0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. Conclusion The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.
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OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.
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Humanos , Farmacología en Red , Quercetina , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Neoplasias Esofágicas , Medicamentos Herbarios ChinosRESUMEN
Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.
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@#Introduction: The ability to self-regulate eating can improve health. This study aimed to determine the relationship between eating self-regulatory skills, diet quantity, and diet quality among Malaysian university students. Methods: This cross-sectional study involved 132 university students. Eating self-regulatory skill was assessed using the Self-Regulation of Eating Behaviour Questionnaire (SREBQ). Dietary intakes from two 24-hour dietary recalls were used to assess diet quantity and quality. Diet quantity was measured as energy and macronutrient intakes, analysed using NutritionistPro. Diet quality was measured using the Malaysian Healthy Eating Index (M-HEI). The relationship between eating self-regulatory skills, diet quantity, and diet quality were evaluated using tests for differences between means and multiple linear regression. Results: Male participants (n=47) consumed more energy than female participants (n=85) (Male: 1850±570 kcal/day, Female: 1596±567 kcal/day, p=0.015). Participants from the Nutrition and Dietetics (N&D) course (n=49) had better M-HEI scores than participants from other health courses (n=83) (N&D course: 52.7±10.5, non-N&D course: 47.2±10.7, p=0.005). The predictors of energy intake were gender (β=-0.193, p=0.023) and SREBQ score (β=- 0.223, p=0.009). Being female and having higher eating self-regulatory skills were associated with lower energy intake. The predictors of diet quality were university course (β=0.240, p=0.005) and SREBQ score (β=0.181, p=0.033). Studying N&D and having higher eating self-regulatory skills were associated with higher M-HEI scores. Conclusion: Higher self-regulation of eating behaviour score is a factor that contributes to lower daily energy intake and higher diet quality score.
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Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.
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Humanos , Mieloma Múltiple/terapia , Estudios Retrospectivos , China , Trasplante de Células Madre Hematopoyéticas , Pronóstico , Trasplante AutólogoRESUMEN
The existing dentin bonding systems based on acid-etching technique lead to the loss of both extrafibrillar and intrafibrillar minerals from dentin collagen, causing excessive demineralization. Because resin monomers can not infiltrate the intrafibrillar spaces of demineralized collagen matrix, degradation of exposed collagen and resin hydrolysis subsequently occur within the hybrid layer, which seriously jeopardizing the longevity of resin-dentin bonding. Collagen extrafibrillar demineralization can effectively avoid the structural defects within the resin-dentin interface caused by acid-etching technique and improve the durability of resin-dentin bonding, by preserving intrafibrillar minerals and selectively demineralizing extrafibrillar dentin. The mechanism and research progress of collagen extrafibrillar demineralization in dentin bonding are reviewed in the paper.
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Humanos , Colágeno , Recubrimiento Dental Adhesivo , Dentina/química , Recubrimientos Dentinarios/química , Ensayo de Materiales , Minerales , Cementos de Resina/química , Desmineralización DentalRESUMEN
Objective To investigate the prevalence and risk factors of hookworm infections among vegetable growers in Anhui Province, so as to provide the evidence for formulating the control strategy and interventions for hookworm human infections.. Methods A total of 1 179 vegetable growers were randomly sampled from 7 counties in Anhui province according to the natural ecological function areas in 2018 and 2019, and the basic features and risk factors of hookworm infections were collected from all subjects using a self-designed questionnaire, including living environment, vegetable planting and fertilization, type of household crops, animal feeding, hygiene and labor habits. In addition, stool samples were collected from all participants, and each stool sample was subjected to twice tests with the Kato-Katz technique. The risk factors of hookworm infections were identified among vegetable growers with the Bayesian log-binomial regression model. Results The prevalence of hookworm infection was 3.90% among the 1 179 vegetable growers. The prevalence of hookworm infection was 10.07% (15/149) among unemployed subjects, 5.32% (31/583) among farmers, and 0 among full-time vegetable growers (0/377) and subjects with other occupations (0/70), and there was a significant difference among subjects in terms of occupation (χ2=36.37, P < 0.01). Bayesian log-binomial regression analysis showed that fertilization with human feces [relative risk (RR)=18.25, 95% confidence interval (CI): (4.31, 77.17)], barefoot labor in vegetable fields [RR=2.86, 95% CI: (1.43, 5.70)], and living in plain ecological areas along the middle and lower reaches of the Yangtze River [RR=4.19, 95% CI: (1.19, 14.81)] were independent risk factors of hookworm infections among vegetable growers. Stratified analysis showed that fertilization with human feces, barefoot labor in vegetable fields, drinking well water or mountain spring, and living in plain ecological areas along the middle and lower reaches of the Yangtze River were independent risk factors of hookw, orm infection among farmers, and living in plain ecological areas along the middle and lower reaches of the Yangtze River and growing rice were independent risk factors of hookw, orm infection among unemployed individuals. Conclusions The prevalence of hookworm infection is high among vegetable growers in Anhui Province, and fertilization with human feces, barefoot labor in vegetable fields and living in plain ecological areas along the middle and lower reaches of the Yangtze River are risk factors of hookw, orm infections among vegetable growers.
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Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations of the GLA gene, resulting in the decreased a-galactosidase A activity and the accumulation of its substrate globotriasylceramide (GL-3) in the heart, kidney and other organs. The main clinical manifestations of cardiac involvement in Fabry disease are left ventricular hypertrophy (LVH), myocardial fibrosis, heart failure and arrhythmia, which limit quality of life and represent the most common causes of death. Following the development of enzyme activity and genetics testing, diagnosis of Fabry disease is no longer difficult. The application of enzyme replacement therapy (ERT) has also significantly slow disease progression. Therefore, early diagnosis and treatment have become essential in the management of Fabry disease cardiac involvement. Electrocardiogram, echocardiography and cardiac magnetic resonance(CMR) allow early detection of suspected patients. In addition, with the approval of oral chaperone therapy and substrate reduction therapy, the Fabry disease specific treatment landscape is evolving. This article will review the general features, pathophysiology, diagnosis and treatment of Fabry disease with cardiac involvement.
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Light chain amyloidosis (AL) is a kind of rare disease. The misfolding of the light chain of monoclonal immunoglobulin forms amyloid substances and deposit in different tissues and organs, resulting in organ dysfunction. The heart involvement is represented as light chain cardiac amyloidosis (AL-CA), leading to heart failure, arrhythmia, myocardial infarction, valvular and pericardial diseases. Cardiac involvement is crucial for the risk stratification and prognosis prediction of patients with AL. The median survival time of AL-CA patients is 24 months and only 6 months for the heart failure patients. In recent years, the prognosis of patients with AL-CA has been significantly improved, thanks to the advancement in diagnosis & treatment strategies of cardiac amyloidosis, the milestone in the breakthroughs in targeted therapy of AL, and the improvement of coordinated multidisciplinary treatment. This paper focuses on the cardiovascular involvement of AL and briefly illustrates the pathogenesis, clinical manifestations, and the diagnosis and treatment of AL-CA.
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Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.
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Humanos , Inteligencia Artificial , Urotelio/patología , Citodiagnóstico , Células Epiteliales/patología , Sensibilidad y Especificidad , Neoplasias Urológicas/orinaRESUMEN
Cerebral small vessel disease (CSVD) is a series of clinical syndrome characterized by the damage of small blood vessels in the brain caused by a variety of causes. Although the pathophysiological mechanisms of CSVD are not fully understood, increasing evidence suggests that matrix metalloproteinase-9 plays an important role in the occurrence and development of CSVD.
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Iron is an essential metal element for human body. It is involved in many important biological metabolic processes. Iron metabolism in the central nervous system has a strict regulatory mechanism. Iron deposition occurs when the homeostasis of iron metabolism is disrupted, leading to an increase in neuronal iron uptake and a decrease in iron discharge. Aging cells develop specific iron deposition, and excessive iron produce reactive oxygen species, which can damage DNA. Highly reactive aldehydes result in irreversible modification of proteins. Stored proteins were stimulated to release iron, which in turn produces more reactive oxygen species, ultimately leading to iron-mediated cell death and neurological dysfunction. The widely used methods for assessing iron deposition include susceptibility weighted imaging and quantitative susceptibility mapping. Abnormally elevated brain iron deposition has been observed in a variety of central nervous system diseases, especially in Parkinson disease. Iron deposition plays an important role in early diagnosis, differential diagnosis, disease evaluation and monitoring and therapeutic effect evaluation of Parkinson disease. This article reviews the research progress of iron deposition in Parkinson disease.
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Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.
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OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
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Ratones , Animales , Receptores del Factor de Necrosis Tumoral/fisiología , Receptores OX40 , Glicoproteínas de Membrana , Ligandos , Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacologíaRESUMEN
Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.By summarizing the clinical manifestations and the electroencephalograhpy,MRI,and pathological features,we aimed to enrich the knowledge about the sCJD with slow progression.