Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Ac...Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.展开更多
Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated ...Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).展开更多
Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,...Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.展开更多
Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation ...Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.展开更多
Objective To investigate the spatial patterns of the prevalence,awareness,treatment,and control rates of dyslipidemia at the provincial level in China.Methods A national and provincial representative cross-sectional s...Objective To investigate the spatial patterns of the prevalence,awareness,treatment,and control rates of dyslipidemia at the provincial level in China.Methods A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in China's Mainland in 2018–2019,using a multi-stage,stratified,cluster-randomized sampling design.Subjects,as households,were selected,followed by a home visit to collect information.Both descriptive and linear regression procedures were applied in the analyses.Results The overall prevalence of dyslipidemia was 35.6%,and wide geographic variations of prevalence,treatment,and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1±13.8 years.The highest-lowest difference regarding the provincial level prevalence rates were 19.7%vs.2.1%for high low-density lipoprotein cholesterol,16.7%vs.2.5%for high total cholesterol,35.9%vs.5.4%for high triglycerides,and 31.4%vs.10.5%for low high-density lipoprotein cholesterol.The treatment rate of dyslipidemia was correlated with the socio-demographic index(P<0.001),urbanization rate(P=0.01),and affordable basic technologies and essential medicines(P<0.001).Conclusion Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence,treatment,and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.展开更多
Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,Br...Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.展开更多
Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactiv...Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.展开更多
Purpose:To reveal the typical features of text duplication in papers from four medical fields:basic medicine,health management,pharmacology and pharmacy,and public health and preventive medicine.To analyze the reasons...Purpose:To reveal the typical features of text duplication in papers from four medical fields:basic medicine,health management,pharmacology and pharmacy,and public health and preventive medicine.To analyze the reasons for duplication and provide suggestions for the management of medical academic misconduct.Design/methodology/approach:In total,2,469 representative Chinese journal papers were included in our research,which were submitted by researchers in 2020 and 2021.A plagiarism check was carried out using the Academic Misconduct Literature Check System(AMLC).We generated a corrected similarity index based on the AMLC general similarity index for further analysis.We compared the similarity indices of papers in four medical fields and revealed their trends over time;differences in similarity index between review and research articles were also analyzed according to the different fields.Further analysis of 143 papers suspected of plagiarism was also performed from the perspective of sections containing duplication and according to the field of research.Findings:Papers in the field of pharmacology and pharmacy had the highest similarity index(8.67±5.92%),which was significantly higher than that in other fields,except health management.The similarity index of review articles(9.77±10.28%)was significantly higher than that of research articles(7.41±6.26%).In total,143 papers were suspected of plagiarism(5.80%)with similarity indices≥15%;most were papers on health management(78,54.55%),followed by public health and preventive medicine(38,26.58%);90.21%of the 143 papers had duplication in multiple sections,while only 9.79%had duplication in a single section.The distribution of sections with duplication varied among different fields;papers in pharmacology and pharmacy were more likely to have duplication in the data/methods and introduction/background sections,however,papers in health management were more likely to contain duplication in the introduction/background or results/discussion sections.Different structures for papers in different fields may have caused these differences.Research limitations:There were three limitations to our research.Firstly,we observed that a small number of papers have been checked early.It is unknown who conducted the plagiarism check as this can be included in other evaluations,such as applications for Science and technology projects or awards.If the authors carried out the check,text with high similarity indices may have been excluded before submission,meaning the similarity index in our research may have been lower than the original value.Secondly,there were only four medical fields included in our research.Additional analysis on a wider scale is required in the future.Thirdly,only a general similarity index was calculated in our study;other similarity indices were not tested.Practical implications:A comprehensive analysis of similarity indices in four medical fields was performed.We made several recommendations for the supervision of medical academic misconduct and the formation of criteria for defining suspected plagiarism for medical papers,as well as for the improved accuracy of text duplication checks.Originality/value:We quantified the differences between the AMLC general similarity index and the corrected index,described the situation around text duplication and plagiarism in papers from four medical fields,and revealed differences in similarity indices between different article types.We also revealed differences in the sections containing duplication for papers with suspected plagiarism among different fields.展开更多
Objective To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction(STEMI)treated with different reperfusion strategies in Chinese county-level hospitals Methods A total of 2,514 ...Objective To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction(STEMI)treated with different reperfusion strategies in Chinese county-level hospitals Methods A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014.The success of fibrinolysis was assessed according to indirect measures of vascular recanalization.The primary outcome was 2-year mortality.Results Reperfusion therapy was used in 1,080 patients(42.9%):fibrinolysis(n=664,61.5%)and primary percutaneous coronary intervention(PCI)(n=416,38.5%).The most common reason for missing reperfusion therapy was a prehospital delay>12 h(43%).Fibrinolysis[14.5%,hazard ratio(HR):0.59,95%confidence interval(CI)0.44–0.80]and primary PCI(6.8%,HR=0.32,95%CI:0.22–0.48)were associated with lower 2-year mortality than those with no reperfusion(28.5%).Among fibrinolysistreated patients,510(76.8%)achieved successful clinical reperfusion;only 17.0%of those with failed fibrinolysis underwent rescue PCI.There was no difference in 2-year mortality between successful fibrinolysis and primary PCI(8.8%vs.6.8%,HR=1.53,95%CI:0.85–2.73).Failed fibrinolysis predicted a similar mortality(33.1%)to no reperfusion(33.1%vs.28.5%,HR=1.30,95%CI:0.93–1.81).Conclusion In Chinese county-level hospitals,only approximately 2/5 of patients with STEMI underwent reperfusion therapy,largely due to prehospital delay.Approximately 30%of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years.Quality improvement initiatives are warranted,especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.展开更多
Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co...Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co-stimulator(ICOS)could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.Methods:We selected 54 formalin-fixed,paraffin-embedded tumor tissues from cases with stage I–III lung adenocarcinoma cancer.Immunohistochemical expression of ICOS and ICOSL was evaluated.The correlation with clinical parameters in Chinese patients was also compared with TCGA results.Results:The positive rates of ICOS and ICOSL were 68%and 81.5%,respectively,in lung tumor tissues.Of these,9 cases had a low expression of ICOS,and 22 cases had a high expression of ICOS;ICOSL expression was low in 20 cases and high in 24 cases.According to the International Association for the Study of Lung Cancer(8th edition),phase I lesions were detected in 21 cases,phase II lesions in 15 cases,and phase III lesions in 18 cases.The median survival time of all patients was 44.5 months,and the median disease-free survival was 32 months.Univariate analysis showed that the factors significantly associated with overall survival were tumor size,regional lymph node involvement,stage,and expression level of ICOS/ICOSL.Survival analysis using log-rank test indicated that the lower ICOS+cell infiltration may predict poor prognosis,whereas lower ICOSL protein expression may be associated with better prognosis,but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.Conclusion:ICOS/ICOSL might be associated with prognosis of lung cancer,and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer.展开更多
Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and re...Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.展开更多
BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.ME...BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.METHODS:A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study.The pregnancy physical activity questionnaire(PPAQ)was used to assess PA,including household/caregiving,occupational,sports/exercise,and transportation activities in the first trimester of pregnancy.The diagnosis of HDP was collected,including gestational hypertension(GH)and preeclampsia(PE).Data were analyzed by unconditional multivariate logistic regression,and the odds ratio(OR)and 95%confi dence interval(CI)were calculated.RESULTS:A total of 178(2.6%)of the 6,820 women were diagnosed with HDP,of which 126(1.8%)were GH and 52(0.8%)were PE.Overall,we found no association between PA in early pregnancy and PE.A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity(MVPA)(adjusted OR 0.54,95%CI 0.31–0.96).No association was observed between PA and HDP in early pregnancy,regardless of diff erent intensities or types of PA.CONCLUSION:MVPA in the first trimester is an influencing factor of HDP.Encouraging pregnant women to engage in MVPA in the fi rst trimester may help to prevent GH.展开更多
Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We establi...Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.展开更多
Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTE...Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.展开更多
Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Altho...Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.展开更多
Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional ce...Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.展开更多
Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation...Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.展开更多
Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(...AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.展开更多
Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effec...Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.展开更多
基金supported by grants of 81530093 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of China+26 种基金supported by grants of 31390431 from the National Natural Science Foundation of Chinasupported by grants of Natural Sciences Foundation of China(31301007 and 81272525)supported by grants of 81622010 from the National Natural Science Foundation of Chinasupported by grants of 81472717 and 81673474 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of Chinasupported by grants of 81400286 and 81530093 from the National Natural Science Foundation of Chinasupported by grants of 81400140 from the National Natural Science Foundation of Chinasupported by grants of 81503128 from the National Natural Science Foundation of China2016I2M-1-008 from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciencessupported by grants of 2014CB542103 from National Basic Research Program of China81502473 from National Natural Science Fund for Young Scholars of Chinasupported by US National Institutes of Health grants (CA217510, CA123088, CA099985, CA193136 and CA152470)supported by grants from the Canadian Institutes of Health Research(FRN 123516 and 152954)the Ontario Institute for Cancer Research(ORBiT)supported by NIH grant GM072744Ministry of Science and Technology of China grant 2016YFA0101100the Fundamental Research Fund for the Central University(No. 2017KFQWJX002) from Huazhong University of Science and TechnologyCore fund (Wang2016) for Development of Cell and Gene Therapy Centre of Academy of Medical Sciences,Zhengzhou UniversityThe MRC (MR/M015696/1)2017YFA0205400 from Ministry of Science and Technology of China2016ZX310190 and 2016ZX320014 from Central Public-interest Scientific Institution Basal Research Fund7162133 from Beijing Natural Science Foundation2016-I2M-4-001 from CAMS Innovation Fund for Medical Sciences2016-I2M-1-007 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1010 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1011 from the CAMS Innovation Fund for Medical Sciences2016-I2M-1008 from CAMS Innovation Fund for Medical Sciences
文摘Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.
文摘Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).
基金National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020013)CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B-049)。
文摘Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.
文摘Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.
基金supported by National Key R&D Program of China[2018YFC1311702,2018YFC1311706]the Chinese central government[key project of public health program]+2 种基金the Fund of"Sanming"Project of Medicine in Shenzhen[SZSM201811096]Young Talent Program of the Academician FundFuwai Hospital Chinese Academy of Medical Sciences,Shenzhen[YS-2020-006]。
文摘Objective To investigate the spatial patterns of the prevalence,awareness,treatment,and control rates of dyslipidemia at the provincial level in China.Methods A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in China's Mainland in 2018–2019,using a multi-stage,stratified,cluster-randomized sampling design.Subjects,as households,were selected,followed by a home visit to collect information.Both descriptive and linear regression procedures were applied in the analyses.Results The overall prevalence of dyslipidemia was 35.6%,and wide geographic variations of prevalence,treatment,and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1±13.8 years.The highest-lowest difference regarding the provincial level prevalence rates were 19.7%vs.2.1%for high low-density lipoprotein cholesterol,16.7%vs.2.5%for high total cholesterol,35.9%vs.5.4%for high triglycerides,and 31.4%vs.10.5%for low high-density lipoprotein cholesterol.The treatment rate of dyslipidemia was correlated with the socio-demographic index(P<0.001),urbanization rate(P=0.01),and affordable basic technologies and essential medicines(P<0.001).Conclusion Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence,treatment,and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.
基金supported by the National Natural Science Foundation of China(82203185,82230058,82172875 and 82073094)the National Key Research and Development Program of China(2021YFF1201300 and 2022YFE0103600)+3 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-014,2021-I2M-1-022,and 2022-I2M-2-001)the Open Issue of State Key Laboratory of Molecular Oncology(SKL-KF-2021-16)the Independent Issue of State Key Laboratory of Molecular Oncology(SKL-2021-16)the Beijing Hope Marathon Special Fund of Chinese Cancer Foundation(LC2020B14).
文摘Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.
基金supported by the National Natural Science Foundation of China,Nos.81941011(to XL),31771053(to HD),31730030(to XL),31971279(to ZY),31900749(to PH),31650001(to XL),31320103903(to XL),31670988(to ZY)the Natural Science Foundation of Beijing,Nos.7222004(to HD)+1 种基金a grant from Ministry of Science and Technology of China,Nos.2017YFC1104002(to ZY),2017YFC1104001(to XL)a grant from Beihang University,No.JKF-YG-22-B001(to FH)。
文摘Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.
基金supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant No.2021-I2M-1-033)。
文摘Purpose:To reveal the typical features of text duplication in papers from four medical fields:basic medicine,health management,pharmacology and pharmacy,and public health and preventive medicine.To analyze the reasons for duplication and provide suggestions for the management of medical academic misconduct.Design/methodology/approach:In total,2,469 representative Chinese journal papers were included in our research,which were submitted by researchers in 2020 and 2021.A plagiarism check was carried out using the Academic Misconduct Literature Check System(AMLC).We generated a corrected similarity index based on the AMLC general similarity index for further analysis.We compared the similarity indices of papers in four medical fields and revealed their trends over time;differences in similarity index between review and research articles were also analyzed according to the different fields.Further analysis of 143 papers suspected of plagiarism was also performed from the perspective of sections containing duplication and according to the field of research.Findings:Papers in the field of pharmacology and pharmacy had the highest similarity index(8.67±5.92%),which was significantly higher than that in other fields,except health management.The similarity index of review articles(9.77±10.28%)was significantly higher than that of research articles(7.41±6.26%).In total,143 papers were suspected of plagiarism(5.80%)with similarity indices≥15%;most were papers on health management(78,54.55%),followed by public health and preventive medicine(38,26.58%);90.21%of the 143 papers had duplication in multiple sections,while only 9.79%had duplication in a single section.The distribution of sections with duplication varied among different fields;papers in pharmacology and pharmacy were more likely to have duplication in the data/methods and introduction/background sections,however,papers in health management were more likely to contain duplication in the introduction/background or results/discussion sections.Different structures for papers in different fields may have caused these differences.Research limitations:There were three limitations to our research.Firstly,we observed that a small number of papers have been checked early.It is unknown who conducted the plagiarism check as this can be included in other evaluations,such as applications for Science and technology projects or awards.If the authors carried out the check,text with high similarity indices may have been excluded before submission,meaning the similarity index in our research may have been lower than the original value.Secondly,there were only four medical fields included in our research.Additional analysis on a wider scale is required in the future.Thirdly,only a general similarity index was calculated in our study;other similarity indices were not tested.Practical implications:A comprehensive analysis of similarity indices in four medical fields was performed.We made several recommendations for the supervision of medical academic misconduct and the formation of criteria for defining suspected plagiarism for medical papers,as well as for the improved accuracy of text duplication checks.Originality/value:We quantified the differences between the AMLC general similarity index and the corrected index,described the situation around text duplication and plagiarism in papers from four medical fields,and revealed differences in similarity indices between different article types.We also revealed differences in the sections containing duplication for papers with suspected plagiarism among different fields.
基金supported by the Twelfth Five-Year Planning Project of the Scientific and Technological Department of China [2011BAI11B02]2014 special fund for scientific research in the public interest by the National Health and Family Planning Commission of the People's Republic of China [No.201402001]CAMS Innovation Fund for Medical Sciences (CIFMS) [2020-I2M-C&T-B-050]。
文摘Objective To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction(STEMI)treated with different reperfusion strategies in Chinese county-level hospitals Methods A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014.The success of fibrinolysis was assessed according to indirect measures of vascular recanalization.The primary outcome was 2-year mortality.Results Reperfusion therapy was used in 1,080 patients(42.9%):fibrinolysis(n=664,61.5%)and primary percutaneous coronary intervention(PCI)(n=416,38.5%).The most common reason for missing reperfusion therapy was a prehospital delay>12 h(43%).Fibrinolysis[14.5%,hazard ratio(HR):0.59,95%confidence interval(CI)0.44–0.80]and primary PCI(6.8%,HR=0.32,95%CI:0.22–0.48)were associated with lower 2-year mortality than those with no reperfusion(28.5%).Among fibrinolysistreated patients,510(76.8%)achieved successful clinical reperfusion;only 17.0%of those with failed fibrinolysis underwent rescue PCI.There was no difference in 2-year mortality between successful fibrinolysis and primary PCI(8.8%vs.6.8%,HR=1.53,95%CI:0.85–2.73).Failed fibrinolysis predicted a similar mortality(33.1%)to no reperfusion(33.1%vs.28.5%,HR=1.30,95%CI:0.93–1.81).Conclusion In Chinese county-level hospitals,only approximately 2/5 of patients with STEMI underwent reperfusion therapy,largely due to prehospital delay.Approximately 30%of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years.Quality improvement initiatives are warranted,especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS,nos:2022-I2M-JB-011,2022-I2M-1-014)the National Natural Science Foundation of China(82293684)the National Key R&D Program of China(2022YFA0806400).
文摘Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co-stimulator(ICOS)could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.Methods:We selected 54 formalin-fixed,paraffin-embedded tumor tissues from cases with stage I–III lung adenocarcinoma cancer.Immunohistochemical expression of ICOS and ICOSL was evaluated.The correlation with clinical parameters in Chinese patients was also compared with TCGA results.Results:The positive rates of ICOS and ICOSL were 68%and 81.5%,respectively,in lung tumor tissues.Of these,9 cases had a low expression of ICOS,and 22 cases had a high expression of ICOS;ICOSL expression was low in 20 cases and high in 24 cases.According to the International Association for the Study of Lung Cancer(8th edition),phase I lesions were detected in 21 cases,phase II lesions in 15 cases,and phase III lesions in 18 cases.The median survival time of all patients was 44.5 months,and the median disease-free survival was 32 months.Univariate analysis showed that the factors significantly associated with overall survival were tumor size,regional lymph node involvement,stage,and expression level of ICOS/ICOSL.Survival analysis using log-rank test indicated that the lower ICOS+cell infiltration may predict poor prognosis,whereas lower ICOSL protein expression may be associated with better prognosis,but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.Conclusion:ICOS/ICOSL might be associated with prognosis of lung cancer,and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer.
基金supported by the National Key R&D Program of China(Grant No.:2017YFC1702003)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant No.:2019e12M-5-078).
文摘Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.
基金supported by Hainan Provincial Natural Science Foundation of China(821QN414,822RC845,821RC557)the Central Guidance on Local Science and Technology Development Fund of Hainan Province(ZY2021HN19)Hainan Clinical Medical Research Center Project(LCYX202205).
文摘BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.METHODS:A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study.The pregnancy physical activity questionnaire(PPAQ)was used to assess PA,including household/caregiving,occupational,sports/exercise,and transportation activities in the first trimester of pregnancy.The diagnosis of HDP was collected,including gestational hypertension(GH)and preeclampsia(PE).Data were analyzed by unconditional multivariate logistic regression,and the odds ratio(OR)and 95%confi dence interval(CI)were calculated.RESULTS:A total of 178(2.6%)of the 6,820 women were diagnosed with HDP,of which 126(1.8%)were GH and 52(0.8%)were PE.Overall,we found no association between PA in early pregnancy and PE.A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity(MVPA)(adjusted OR 0.54,95%CI 0.31–0.96).No association was observed between PA and HDP in early pregnancy,regardless of diff erent intensities or types of PA.CONCLUSION:MVPA in the first trimester is an influencing factor of HDP.Encouraging pregnant women to engage in MVPA in the fi rst trimester may help to prevent GH.
基金National Key Research and Development Program of China(No.2018YFC1705503).
文摘Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.
基金National High Level Hospital Clinical Research Funding(BJ-2018-204,BJ-2023-112)。
文摘Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB).
文摘Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.
基金supported by the National Natural Science Foundation of China(No.81573957,No.81874461 and No.82070307).
文摘Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.
基金supported by grants from the Beijing Nova Program (No. Z201100006820069)CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021-I2M-1-023, 2021-I2M-1-010)Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star)。
文摘Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
基金Supported by Peking Union Medical College Hospital Deposit Integration Commission Funds(No.ZC201904168).
文摘AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.
基金supported by the National Natural Science Foundation of China,No.82171270 (to ZL)Public Service Platform for Artificial In telligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People's Republic of China,No.2020-0103-3-1 (to ZL)+3 种基金the Natural Science Foundation of Beijing,No.Z200016 (to ZL)Beijing Talents Project,No.2018000021223ZK03 (to ZL)Beijing Municipal Committee of Science and Technology,No.Z201 100005620010 (to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029 (to YongW)。
文摘Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.