Background and Objective Patients with glioma experience a high symptom burden and have diverse palliative care needs.However,the assessment scales used in palliative care remain non-standardized and highly heterogene...Background and Objective Patients with glioma experience a high symptom burden and have diverse palliative care needs.However,the assessment scales used in palliative care remain non-standardized and highly heterogeneous.To evaluate the application patterns of the current scales used in palliative care for glioma,we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care.Methods We conducted a systematic search of five databases including PubMed,Web of Science,Medline,EMBASE,and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care.We extracted data on scale characteristics,domains,frequency,and psychometric properties.Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools.Results Of the 3,405 records initially identified,72 studies were included.These studies contained 75 distinct scales that were used 193 times.Mood(21.7%),quality of life(24.4%),and supportive care needs(5.2%)assessments were the most frequently assessed items,exceeding half of all scale applications.Among the various assessment dimensions,the Distress Thermometer(DT)was the most frequently used tool for assessing mood,while the Short Form-36 Health Survey Questionnaire(SF-36)was the most frequently used tool for assessing quality of life.The Mini Mental Status Examination(MMSE)was the most common tool for cognitive assessment.Performance status(5.2%)and social support(6.8%)were underrepresented.Only three brain tumor-specific scales were identified.Caregiver-focused scales were limited and predominantly burden-oriented.Conclusions There are significant heterogeneity,domain imbalances,and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care.The scale selected for use should be comprehensive and user-friendly.展开更多
Objective:Gemcitabine plus nab-paclitaxel(GnP)is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma(PDAC).S-1,an oral fluoropyrimidine derivative,as compared with gemcitabine,is non-inferior...Objective:Gemcitabine plus nab-paclitaxel(GnP)is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma(PDAC).S-1,an oral fluoropyrimidine derivative,as compared with gemcitabine,is non-inferior in terms of overall survival(OS)and is associated with lower hematologic toxicity.Accordingly,S-1 is a convenient oral alternative treatment for advanced PDAC.This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1(GS)vs.GnP as first-line chemotherapy for advanced PDAC.Methods:Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated.Results:A total of 300 patients were assessed,of whom 84 received GS and 216 received GnP.The chemotherapy completion rate was higher with GS than GnP(50.0%vs.30.3%,P=0.0028).The objective response rate(ORR)was slightly higher(14.3%vs.9.7%,P=0.35),and the median OS was significantly longer(17.9 months vs.13.3 months,P=0.0078),in the GS group than the GnP group.However,the median progression-free survival(PFS)did not significantly differ between groups.Leukopenia risk was significantly lower in the GS group than the GnP group(14.9%vs.28.1%,P=0.049).Conclusions:As first-line chemotherapy for advanced PDAC,the GS regimen led to a significantly longer OS than the GnP regimen.The PFS,ORR,and incidence of severe adverse events were comparable between the GS and GnP groups.展开更多
There is great heterogeneity among inflammatory bowel disease(IBD)patients in terms of pathogenesis,clinical manifestation,response to treatment,and prognosis,which requires the individualized and precision management...There is great heterogeneity among inflammatory bowel disease(IBD)patients in terms of pathogenesis,clinical manifestation,response to treatment,and prognosis,which requires the individualized and precision management of patients.Many studies have focused on prediction biomarkers and models for assessing IBD disease type,activity,severity,and prognosis.During the era of biologics,how to predict the response and side effects of patients to different treatments and how to quickly recognize the loss of response have also become important topics.Multiomics is a promising area for investigating the complex network of IBD pathogenesis.Integrating numerous amounts of data requires the use of artificial intelligence.展开更多
Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,an...Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September 2023.Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified.We estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the curve.Results Four studies were included.The pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for IBS.However,limited high-quality data make the results'validity and applicability questionable.There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.展开更多
Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were deri...Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.POAG data were sourced from the largest FinnGen study,comprising 8,530 DR cases and 391,275 European controls.A two-sample MR analysis,supplemented by bidirectional MR,Bayesian co-localization analysis,and phenotype scanning,was conducted to examine the causal relationships between plasma proteins and POAG.The analysis was validated by identifying associations between plasma proteins and POAG-related traits,including intraocular pressure(IOP),retinal nerve fibre layer(RNFL),and ganglion cell and inner plexiform layer(GCIPL).By searching druggable gene lists,the ChEMBL database,and the ClinicalTrials.gov database,the druggability and clinical development activity of the identified proteins were systematically evaluated.Results:Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments.The ORs per standard deviation increase in protein levels ranged from 0.39(95%CI:0.24–0.62;P=7.70×10^(-5))for phospholipase C gamma 1(PLCG1)to 1.29(95%CI:1.16–1.44;P=6.72×10^(-6))for nidogen-1(NID1).Bidirectional MR indicated that reverse causality did not interfere with the results of the main MR analyses.Five proteins exhibited strong co-localization evidence(PH4≥0.8):protein sel-1 homolog 1(SEL1L),tyrosine-protein kinase receptor UFO(AXL),nidogen-1(NID1)and FAD-linked sulfhydryl oxidase ALR(GFER)were negatively associated with POAG risk,while roundabout homolog 1(ROBO1)showed a positive association.The phenotype scanning did not reveal any confounding factors between pQTLs and POAG.Further,validation analyses identified nine proteins causally related to POAG traits,with five proteins including interleukin-18 receptor 1(IL18R1),interleukin-1 receptor type 1(IL1R1),phospholipase C gamma 1(PLCG1),ribonuclease pancreatic(RNASE1),serine protease inhibitor Kazal-type 6(SPINK6)revealing consistent directional associations.In addition,18 causal proteins were highlighted for their druggability,of which 5 proteins are either already approved drugs or in clinical trials and 13 proteins are novel drug targets.Conclusions:This study identifies 18 plasma proteins as potential therapeutic targets for POAG,particularly emphasizing the role of genomic and proteomic integration in drug discovery.Future experimental and clinical studies should be conducted to validate the efficacy of these proteins and to conduct more comprehensive proteomic explorations,thus taking a significant leap toward innovative POAG treatments.展开更多
Objective: Erectile dysfunction (ED) is a condition of insufficient penile erection, consistently or recurrently, for sexual activity. Tumor necrosis factor-alpha (TNF-α) induces transforming growth factor-beta (TGF-...Objective: Erectile dysfunction (ED) is a condition of insufficient penile erection, consistently or recurrently, for sexual activity. Tumor necrosis factor-alpha (TNF-α) induces transforming growth factor-beta (TGF-β), which causes the transition of epithelial cells into mesenchymal cells that affect ED. This study aimed to evaluate the roles of TNF-α, TGF-β, degree of lower urinary tract symptoms, and prostatic volume for the presence of ED in benign prostatic hyperplasia (BPH) patients.Methods: Our study performed an analytic observational retrospective cohort study using secondary data from four hospitals in Bali, Indonesia, including medical records and other administrative data. The sample was BPH patients with several history qualifications.Results: Our sample was 83 respondents, ranging from 50 years to 80 years, 61 respondents with ED and 22 with non-ED. The International Prostate Symptom Score showed a significant result, which indicates that ED is more common in patients with higher International Prostate Symptom Score (p=0.002). Moreover, the TNF-α of ≥43.9 pg/mg and TGF-β of ≥175.8 pg/mL were significantly associated with the presence of ED in BPH patients (p<0.0001). Despite these results, prostate volume is not significant with ED (p=0.947).Conclusion: TNF-α, TGF-β, and lower urinary tract symptoms severity can predict the occurrence of ED in BPH, while prostatic volume was not significant.展开更多
Atopic dermatitis(AD)is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching.The colonization of Staphylococcus aureus(S.aureus)is correlated with the se...Atopic dermatitis(AD)is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching.The colonization of Staphylococcus aureus(S.aureus)is correlated with the severity of the disease,but its role in AD development remains elusive.Using single-cell RNA sequencing,we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S.aureus(MRSA).Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology.Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march.Mechanistically,IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33,which in turn aggravated type 2 immunity and AD-like skin conditions.Overall,these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.展开更多
Diabetic wounds are characterized by chronic inflammation,vascular insufficiency,and peripheral neuropathy,which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration.Ho...Diabetic wounds are characterized by chronic inflammation,vascular insufficiency,and peripheral neuropathy,which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration.However,strategies targeting neurovascular regeneration remain limited.Here,we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modifiedε-poly-L-lysine(S-GPL),cofunctionalized with VEGF-mimetic peptide(KLT)and BDNF-mimetic peptide(RGI).The sprayable format con-forms to irregular wound geometries,while the pneumatic spraying technique generates high-pressure micro-bubbles that create a porous structure,thereby enhancing exudate absorption and sustained peptide release as a sponge dressing.Additionally,the incorporation of KLT and RGI facilitates the reconstruction of the neuro-vascular microenvironment.In vitro,KLT promoted endothelial cell maturation and cytokine secretion,whereas RGI enhanced Schwann cell activity.Notably,S-GPL^(KLT/RGI) facilitated intercellular interactions between RSCs and HUVECs,highlighting the cellular mechanisms underlying neurovascular communication.In a full-thickness diabetic wound model in rats,the hydrogel accelerated wound closure,re-epithelialization,and matrix remodeling.These effects were accompanied by enhanced neovascularization and axonal regeneration,along with the formation of a spatially organized neurovascular niche,as evidenced by CD31^(+)capillaries closely aligned with PGP9.5^(+)nerve fibers.Building upon the intrinsic anti-inflammatory properties of S-GPL,tran-scriptomic and immunohistochemical analyses further revealed that S-GPL^(KLT/RGI) treatment suppressed the IL-17 signaling pathway.However,the relationship between immunomodulation and neurovascular reconstruction warrants further investigation.Collectively,this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation,offering a clinically translatable strategy for diabetic wound management.展开更多
To the Editor:Diagnosing Alzheimer’s disease(AD)remains challenging,as clinical diagnostic accuracy is often inferior to neuropathological confirmation.The AT(N)system,introduced by the National Institute on Aging-Al...To the Editor:Diagnosing Alzheimer’s disease(AD)remains challenging,as clinical diagnostic accuracy is often inferior to neuropathological confirmation.The AT(N)system,introduced by the National Institute on Aging-Alzheimer’s Association(NIA-AA),provides a biomarker framework to increase diagnostic precision in AD research.[1]Recent technological innovations,such as ultrasensitive assays like Single Molecule Array(Simoa),have enabled precise evaluation of blood biomarkers,offering potential for noninvasive diagnostics.展开更多
To the Editor:Thrombotic microangiopathy(TMA)is an uncommon hematological involvement in systemic lupus erythematosus(SLE)patients with an estimated incidence of 0.5–1.0%,including but not limited to thrombotic throm...To the Editor:Thrombotic microangiopathy(TMA)is an uncommon hematological involvement in systemic lupus erythematosus(SLE)patients with an estimated incidence of 0.5–1.0%,including but not limited to thrombotic thrombocytopenic purpura(TTP),hemolytic uremic syndrome(HUS),and other secondary conditions.SLE-TMA has a rapid onset and poor prognosis,manifesting as microvascular thrombosis,thrombocytopenia,and microangiopathic hemolytic anemia.[1]Based on the Chinese SLE Treatment and Research Group(CSTAR)registry,we aimed to summarize clinical characteristics and explore prognostic risk factors in SLE-TMA patients through a retrospective multicenter study.展开更多
Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study ai...Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.展开更多
Background:Uterine fibroids(UFs),the most common tumors in women worldwide,may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients,causing significant s...Background:Uterine fibroids(UFs),the most common tumors in women worldwide,may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients,causing significant societal health and financial burdens.The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods:Data on the incidence,prevalence,disability-adjusted life years(DALYs),age-standardized incidence rates(ASIRs),age-standardized prevalence rates(ASPRs),and age-standardized DALY rates for UFs were collected,and the associations with the Human Development Index(HDI)and fertility were evaluated.The age trends in the average annual percent change(AAPC)of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis.The associations between lifestyle,metabolic,and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results:The worldwide incidence and prevalence of UFs have been increasing in the past decade,with AAPCs of 0.27%in the incidence rate and 0.078%in the prevalence rate.During 2010–2019,significant increasing trends in UF ASIR were observed in 52 of 88 countries.The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45–54-year-old women which showed no significant trend.Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility.The incidence of UFs was positively correlated with alcohol intake,hypertension,overweight,and obesity and negatively correlated with smoking.Conclusion:With the increasing incidence and prevalence worldwide,effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.展开更多
Introduction Primary hyperparathyroidism(PHPT)is caused by hyperfunctioning parathyroid adenoma,hyperplasia,or carcinoma.Parathyroid carcinoma is a rare disease affecting<1%of PHPT patients and is associated with c...Introduction Primary hyperparathyroidism(PHPT)is caused by hyperfunctioning parathyroid adenoma,hyperplasia,or carcinoma.Parathyroid carcinoma is a rare disease affecting<1%of PHPT patients and is associated with complications such as acute pancreatitis(AP),which can be complicated by pregnancy[1].Currently,pregnant patients with AP or PHPT can only be treated empirically as there is no consensus approach.Here,we report a rare case of parathyroid carcinoma with adenomarelated AP during pregnancy.The detailed diagnosis and treatment process are described,and clinical features of similar cases are summarized.We hope to improve the diagnosis and treatment of PHPT-related pancreatitis during pregnancy.展开更多
Dear Editor,Mayer-Rokitansky-Küster-Hauser(MRKH)syndrome is a rare congenital disease characterized by the hypoplastic uterus and vagina in women with a normal female karyotype(46,XX)and phenotype.Although some g...Dear Editor,Mayer-Rokitansky-Küster-Hauser(MRKH)syndrome is a rare congenital disease characterized by the hypoplastic uterus and vagina in women with a normal female karyotype(46,XX)and phenotype.Although some genes and mutations,such as WNT4.展开更多
Patient‐centered care(PCC)is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients'experience during the management of their disease.However,despite growing interest,th...Patient‐centered care(PCC)is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients'experience during the management of their disease.However,despite growing interest,the concept and specifics of PCC remain unclear.This consensus document addresses this gap by providing a literature review and a clear definition of PCC and outlines its main components as observed in real‐world practice.These components include daytime diagnostic and treatment procedures,in‐hospital and community‐based infusion centers,home‐based diagnostic and treatment services,smart healthcare solutions,and integration of traditional Chinese medicine.This document delves into the implementation of PCC and explores its potential benefits.展开更多
Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitatio...Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.展开更多
Secondary sclerosing cholangitis(SSC)is a chronic biliary disease characterized by inflammatory responses,fibrous occlusion,strictures,and progressive destruction of intrahepatic and/or extrahepatic bile ducts,which m...Secondary sclerosing cholangitis(SSC)is a chronic biliary disease characterized by inflammatory responses,fibrous occlusion,strictures,and progressive destruction of intrahepatic and/or extrahepatic bile ducts,which may lead to cholestasis and cirrhosis(1).Well-described causes of SSC include infectious,ischemic,toxic,immunologic,congenital disorders and so on(2,3).Here,we presented a rare case of sclerosing cholangitis secondary to acute severe biliary pancreatitis.展开更多
Alternative polyadenylation(APA)is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites(PASs).APA is involved in lymphocyte activation;however,i...Alternative polyadenylation(APA)is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites(PASs).APA is involved in lymphocyte activation;however,its role throughout the entire differentiation trajectory remains elusive.Here,we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells(HSPCs)to terminally differentiated lymphocytes.This analysis covered 19973 cells of 12 clusters from five lineages(B cells,CD4^(+)T cells,CD8^(+)T cells,natural killer cells,and plasmacytoid dendritic cells).A total of 2364 genes exhibited differential 3'-untranslated region(3'UTR)PAS usage,and 3021 genes displayed differential intronic cleavage during lymphoid differentiation.We observed a global trend of 3'UTR shortening during lymphoid differentiation.Nevertheless,specific events of both 3'UTR shortening and lengthening were also identified within each cluster.The APA patterns delineated three differentiation stages:HSPCs,precursor cells,and mature cells.Moreover,we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes(TCF7 and NFATC2IP),immune function-related genes(BCL2,CD5,CD28,GOLT1B,and TMEM59),and protein ubiquitination-related genes(UBE2G1,YPEL5,and SUMO3).These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.展开更多
Background:The optimal regimen of infliximab salvage in acute severe ulcerative colitis(ASUC)patients remains controversial.This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC pat...Background:The optimal regimen of infliximab salvage in acute severe ulcerative colitis(ASUC)patients remains controversial.This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients,and to explore risk factors and concrete accelerated regimens for them.Methods:Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China.Outcomes including colectomy and clinical remission(Mayo score≤2 and every subscore≤1 at Day 14)rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjust-ment for potential confounders.The dose-response relationship was explored by plotting restricted cubic splines.Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes.A systematic re-view and meta-analysis was also performed.Results:A total of 76 patients were analysed:29 received standard and 47 received accelerated induction.The accelerated group had a higher 90-day colectomy rate(17.8%vs 0%,P=0.019)and lower clinical remission rate(27.7%vs 65.5%,P=0.001).After adjust-ing for propensity score and institution,there was no significant difference in colectomy or clinical remission rates(both P>0.05).Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days,with no improve-ment observed for increasing cumulative infliximab dosage within 28 days.Multivariate logistic regression analyses revealed C-reac-tive protein of>10 mg/L at infliximab initiation(odds ratio?5.00,95%confidence interval:1.27-24.34)as an independent risk factor for no clinical remission.Meta-analysis also revealed no significant difference in colectomy rates at 3 months(P=0.54).Conclusions:After adjusting for confounders,there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients.Early administration of an intensified dosage within 5 days may be beneficial.Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.展开更多
Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supporte...Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supported by high-quality evidence.However,the TB indications and strategies are controversial.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,invited a panel of recognized urology experts in PCa to address these topics at the Panjiayuan Consensus Conference 2022.The conference results on prostate TB are presented herein.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences identified 10 key areas of prostate biopsy:(1)selection of imaging examination;(2)indications of TB;(3)transperineal and transrectal prostate biopsy;(4)TB pathways;(5)TB and SB;(6)three techniques of TB;(7)the number of TB cores needed for one lesion;(8)core number for SB;(9)free-hand TB;(10)future development of TB/prostate diagnosis.Thus,a panel of 25 recognized urologists and 2 radiologists from China were invited to attend this conference.The panel voted anonymously on 14 predetermined questions.Voting was based on the panelists'clinical practice and opinion,rather than high-level evidence.The voting outcomes were supported by the panel unequally,and details of the voting results were reported.The voting results can help clinicians to decide on biopsy timing and proper strategies,for which guidelines are sparse.We also focused on the future development of TB and SB,such as the combined pathway of TB and SB,techniques of TB,biopsy cores,free-hand TB,and prostate-specific membrane antigen positron emission tomography/computed tomography.展开更多
文摘Background and Objective Patients with glioma experience a high symptom burden and have diverse palliative care needs.However,the assessment scales used in palliative care remain non-standardized and highly heterogeneous.To evaluate the application patterns of the current scales used in palliative care for glioma,we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care.Methods We conducted a systematic search of five databases including PubMed,Web of Science,Medline,EMBASE,and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care.We extracted data on scale characteristics,domains,frequency,and psychometric properties.Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools.Results Of the 3,405 records initially identified,72 studies were included.These studies contained 75 distinct scales that were used 193 times.Mood(21.7%),quality of life(24.4%),and supportive care needs(5.2%)assessments were the most frequently assessed items,exceeding half of all scale applications.Among the various assessment dimensions,the Distress Thermometer(DT)was the most frequently used tool for assessing mood,while the Short Form-36 Health Survey Questionnaire(SF-36)was the most frequently used tool for assessing quality of life.The Mini Mental Status Examination(MMSE)was the most common tool for cognitive assessment.Performance status(5.2%)and social support(6.8%)were underrepresented.Only three brain tumor-specific scales were identified.Caregiver-focused scales were limited and predominantly burden-oriented.Conclusions There are significant heterogeneity,domain imbalances,and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care.The scale selected for use should be comprehensive and user-friendly.
基金supported by grants from National High Level Hospital Clinical Research Funding(Grant Nos.2022-PUMCH-D-001 and 2022-PUMCH-A-213)。
文摘Objective:Gemcitabine plus nab-paclitaxel(GnP)is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma(PDAC).S-1,an oral fluoropyrimidine derivative,as compared with gemcitabine,is non-inferior in terms of overall survival(OS)and is associated with lower hematologic toxicity.Accordingly,S-1 is a convenient oral alternative treatment for advanced PDAC.This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1(GS)vs.GnP as first-line chemotherapy for advanced PDAC.Methods:Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated.Results:A total of 300 patients were assessed,of whom 84 received GS and 216 received GnP.The chemotherapy completion rate was higher with GS than GnP(50.0%vs.30.3%,P=0.0028).The objective response rate(ORR)was slightly higher(14.3%vs.9.7%,P=0.35),and the median OS was significantly longer(17.9 months vs.13.3 months,P=0.0078),in the GS group than the GnP group.However,the median progression-free survival(PFS)did not significantly differ between groups.Leukopenia risk was significantly lower in the GS group than the GnP group(14.9%vs.28.1%,P=0.049).Conclusions:As first-line chemotherapy for advanced PDAC,the GS regimen led to a significantly longer OS than the GnP regimen.The PFS,ORR,and incidence of severe adverse events were comparable between the GS and GnP groups.
基金the Youth Program of National Natural Science Foundation of China,No.82000526the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-A-072the National College Students’Innovation and Entrepreneurship Training Program,No.2022zglc06083.
文摘There is great heterogeneity among inflammatory bowel disease(IBD)patients in terms of pathogenesis,clinical manifestation,response to treatment,and prognosis,which requires the individualized and precision management of patients.Many studies have focused on prediction biomarkers and models for assessing IBD disease type,activity,severity,and prognosis.During the era of biologics,how to predict the response and side effects of patients to different treatments and how to quickly recognize the loss of response have also become important topics.Multiomics is a promising area for investigating the complex network of IBD pathogenesis.Integrating numerous amounts of data requires the use of artificial intelligence.
基金funded by the National Natural Science Foundation of China(No.32170788)National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-023)Beijing Natural Science Foundation(No.7232123).
文摘Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September 2023.Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified.We estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the curve.Results Four studies were included.The pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for IBS.However,limited high-quality data make the results'validity and applicability questionable.There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.
基金supported by the Hainan Province Clinical Medical Center,the National Natural Science Foundation of China(82171084,82371086).
文摘Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.POAG data were sourced from the largest FinnGen study,comprising 8,530 DR cases and 391,275 European controls.A two-sample MR analysis,supplemented by bidirectional MR,Bayesian co-localization analysis,and phenotype scanning,was conducted to examine the causal relationships between plasma proteins and POAG.The analysis was validated by identifying associations between plasma proteins and POAG-related traits,including intraocular pressure(IOP),retinal nerve fibre layer(RNFL),and ganglion cell and inner plexiform layer(GCIPL).By searching druggable gene lists,the ChEMBL database,and the ClinicalTrials.gov database,the druggability and clinical development activity of the identified proteins were systematically evaluated.Results:Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments.The ORs per standard deviation increase in protein levels ranged from 0.39(95%CI:0.24–0.62;P=7.70×10^(-5))for phospholipase C gamma 1(PLCG1)to 1.29(95%CI:1.16–1.44;P=6.72×10^(-6))for nidogen-1(NID1).Bidirectional MR indicated that reverse causality did not interfere with the results of the main MR analyses.Five proteins exhibited strong co-localization evidence(PH4≥0.8):protein sel-1 homolog 1(SEL1L),tyrosine-protein kinase receptor UFO(AXL),nidogen-1(NID1)and FAD-linked sulfhydryl oxidase ALR(GFER)were negatively associated with POAG risk,while roundabout homolog 1(ROBO1)showed a positive association.The phenotype scanning did not reveal any confounding factors between pQTLs and POAG.Further,validation analyses identified nine proteins causally related to POAG traits,with five proteins including interleukin-18 receptor 1(IL18R1),interleukin-1 receptor type 1(IL1R1),phospholipase C gamma 1(PLCG1),ribonuclease pancreatic(RNASE1),serine protease inhibitor Kazal-type 6(SPINK6)revealing consistent directional associations.In addition,18 causal proteins were highlighted for their druggability,of which 5 proteins are either already approved drugs or in clinical trials and 13 proteins are novel drug targets.Conclusions:This study identifies 18 plasma proteins as potential therapeutic targets for POAG,particularly emphasizing the role of genomic and proteomic integration in drug discovery.Future experimental and clinical studies should be conducted to validate the efficacy of these proteins and to conduct more comprehensive proteomic explorations,thus taking a significant leap toward innovative POAG treatments.
文摘Objective: Erectile dysfunction (ED) is a condition of insufficient penile erection, consistently or recurrently, for sexual activity. Tumor necrosis factor-alpha (TNF-α) induces transforming growth factor-beta (TGF-β), which causes the transition of epithelial cells into mesenchymal cells that affect ED. This study aimed to evaluate the roles of TNF-α, TGF-β, degree of lower urinary tract symptoms, and prostatic volume for the presence of ED in benign prostatic hyperplasia (BPH) patients.Methods: Our study performed an analytic observational retrospective cohort study using secondary data from four hospitals in Bali, Indonesia, including medical records and other administrative data. The sample was BPH patients with several history qualifications.Results: Our sample was 83 respondents, ranging from 50 years to 80 years, 61 respondents with ED and 22 with non-ED. The International Prostate Symptom Score showed a significant result, which indicates that ED is more common in patients with higher International Prostate Symptom Score (p=0.002). Moreover, the TNF-α of ≥43.9 pg/mg and TGF-β of ≥175.8 pg/mL were significantly associated with the presence of ED in BPH patients (p<0.0001). Despite these results, prostate volume is not significant with ED (p=0.947).Conclusion: TNF-α, TGF-β, and lower urinary tract symptoms severity can predict the occurrence of ED in BPH, while prostatic volume was not significant.
基金supported by the National Key R&D Program of China(2023YFC2306300)the National Natural Science Foundation of China(Grant Nos.32225019,92357304,and 32394003)supported by the Center for Life Sciences,the Institute for Immunology,and School of Basic Medical Sciences at Tsinghua University.
文摘Atopic dermatitis(AD)is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching.The colonization of Staphylococcus aureus(S.aureus)is correlated with the severity of the disease,but its role in AD development remains elusive.Using single-cell RNA sequencing,we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S.aureus(MRSA).Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology.Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march.Mechanistically,IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33,which in turn aggravated type 2 immunity and AD-like skin conditions.Overall,these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
基金supported by Beijing Natural Science Foundation of China(L254044,L244061,L244062,L234075)National Natural Sci-ence Foundation of China(82472565,82302828,32401140,32271414)+3 种基金Plastic Medicine Research Fund of Chinese Academy of Medical Sciences(2024-ZX-1-02,2024-ZX-1-03)National High Level Hospital Clinical Research Funding(2025-PUMCH-D-001,2022-PUMCH-C-025,2022-PUMCH-B-041,2022-PUMCH-A-025,2022-PUMCH-A-210)National Key R&D Program of China(2024YFC3405800,2024YFC3405801)Peking Union Medical Col-lege Hospital Talent Cultivation Program(Category C)No.UBJ11557.
文摘Diabetic wounds are characterized by chronic inflammation,vascular insufficiency,and peripheral neuropathy,which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration.However,strategies targeting neurovascular regeneration remain limited.Here,we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modifiedε-poly-L-lysine(S-GPL),cofunctionalized with VEGF-mimetic peptide(KLT)and BDNF-mimetic peptide(RGI).The sprayable format con-forms to irregular wound geometries,while the pneumatic spraying technique generates high-pressure micro-bubbles that create a porous structure,thereby enhancing exudate absorption and sustained peptide release as a sponge dressing.Additionally,the incorporation of KLT and RGI facilitates the reconstruction of the neuro-vascular microenvironment.In vitro,KLT promoted endothelial cell maturation and cytokine secretion,whereas RGI enhanced Schwann cell activity.Notably,S-GPL^(KLT/RGI) facilitated intercellular interactions between RSCs and HUVECs,highlighting the cellular mechanisms underlying neurovascular communication.In a full-thickness diabetic wound model in rats,the hydrogel accelerated wound closure,re-epithelialization,and matrix remodeling.These effects were accompanied by enhanced neovascularization and axonal regeneration,along with the formation of a spatially organized neurovascular niche,as evidenced by CD31^(+)capillaries closely aligned with PGP9.5^(+)nerve fibers.Building upon the intrinsic anti-inflammatory properties of S-GPL,tran-scriptomic and immunohistochemical analyses further revealed that S-GPL^(KLT/RGI) treatment suppressed the IL-17 signaling pathway.However,the relationship between immunomodulation and neurovascular reconstruction warrants further investigation.Collectively,this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation,offering a clinically translatable strategy for diabetic wound management.
基金This study was supported by grants from the National Key Research and Development Program of China(Nos.2020YFA0804500 and 2020YFA0804501)CAMS Innovation fund for medical sciences(CIFMS)(Nos.2021-I2M-1-020 and 2020-I2M-C&T-B-010)+1 种基金National Natural Science Foundation of China(Nos.81550021 and 30470618)National High Level Hospital Clinical Research Funding(Nos.2022-PUMCH-D-007 and 2022-PUMCH-A-254).
文摘To the Editor:Diagnosing Alzheimer’s disease(AD)remains challenging,as clinical diagnostic accuracy is often inferior to neuropathological confirmation.The AT(N)system,introduced by the National Institute on Aging-Alzheimer’s Association(NIA-AA),provides a biomarker framework to increase diagnostic precision in AD research.[1]Recent technological innovations,such as ultrasensitive assays like Single Molecule Array(Simoa),have enabled precise evaluation of blood biomarkers,offering potential for noninvasive diagnostics.
基金supported by the Chinese National Key Technology R&D Program,Ministry of Science and Technology(No.2021YFC2501300)Beijing Municipal Science&Technology Commission(Nos.Z201100005520022,Z201100005520023,Z201100005520025,Z201100005520026,and Z201100005520027)+2 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-I2M-1-005,2022-I2M-1-004,and 2023-I2M-2-005)National High-Level Hospital Clinical Research Funding(Nos.2022-PUMCH-B-013,2022-PUMCH-C-002,and 2022-PUMCH-D-009)Peking Union Medical College Student Innovation Training Project(No.2023zg1c06017).
文摘To the Editor:Thrombotic microangiopathy(TMA)is an uncommon hematological involvement in systemic lupus erythematosus(SLE)patients with an estimated incidence of 0.5–1.0%,including but not limited to thrombotic thrombocytopenic purpura(TTP),hemolytic uremic syndrome(HUS),and other secondary conditions.SLE-TMA has a rapid onset and poor prognosis,manifesting as microvascular thrombosis,thrombocytopenia,and microangiopathic hemolytic anemia.[1]Based on the Chinese SLE Treatment and Research Group(CSTAR)registry,we aimed to summarize clinical characteristics and explore prognostic risk factors in SLE-TMA patients through a retrospective multicenter study.
基金supported by the National Natural Science Foundation of China(81830043,81771561)the National High Level Hospital Clinical Research Funding(2022-PUMCH-A-113,2022-PUMCH-C-031)+1 种基金the National Key Research and Development Program of China(2018YFC2002201)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT320-003)。
文摘Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.
基金supported by grants from the National High level Hospital Clinical Research Funding(No.2022-PUMCH-A-067)National Natural Science Foundation of China(No.82272724)Beijing Municipal Natural Science Foundation(No.Z220013).
文摘Background:Uterine fibroids(UFs),the most common tumors in women worldwide,may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients,causing significant societal health and financial burdens.The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods:Data on the incidence,prevalence,disability-adjusted life years(DALYs),age-standardized incidence rates(ASIRs),age-standardized prevalence rates(ASPRs),and age-standardized DALY rates for UFs were collected,and the associations with the Human Development Index(HDI)and fertility were evaluated.The age trends in the average annual percent change(AAPC)of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis.The associations between lifestyle,metabolic,and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results:The worldwide incidence and prevalence of UFs have been increasing in the past decade,with AAPCs of 0.27%in the incidence rate and 0.078%in the prevalence rate.During 2010–2019,significant increasing trends in UF ASIR were observed in 52 of 88 countries.The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45–54-year-old women which showed no significant trend.Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility.The incidence of UFs was positively correlated with alcohol intake,hypertension,overweight,and obesity and negatively correlated with smoking.Conclusion:With the increasing incidence and prevalence worldwide,effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.
基金supported by National High-Level Hospital Clinical Research Funding(2022-PUMCH-A-020)the Undergraduate Teaching Reform and Innovation Project(2022zlgc0108)Beijing’s Key Construction of First-class Majors(2021zlgc1106).
文摘Introduction Primary hyperparathyroidism(PHPT)is caused by hyperfunctioning parathyroid adenoma,hyperplasia,or carcinoma.Parathyroid carcinoma is a rare disease affecting<1%of PHPT patients and is associated with complications such as acute pancreatitis(AP),which can be complicated by pregnancy[1].Currently,pregnant patients with AP or PHPT can only be treated empirically as there is no consensus approach.Here,we report a rare case of parathyroid carcinoma with adenomarelated AP during pregnancy.The detailed diagnosis and treatment process are described,and clinical features of similar cases are summarized.We hope to improve the diagnosis and treatment of PHPT-related pancreatitis during pregnancy.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020PT320-003,2021-PT320-001)the National Natural Science Foundation of China(81830043)。
文摘Dear Editor,Mayer-Rokitansky-Küster-Hauser(MRKH)syndrome is a rare congenital disease characterized by the hypoplastic uterus and vagina in women with a normal female karyotype(46,XX)and phenotype.Although some genes and mutations,such as WNT4.
基金CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2021‐I2M‐1‐014。
文摘Patient‐centered care(PCC)is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients'experience during the management of their disease.However,despite growing interest,the concept and specifics of PCC remain unclear.This consensus document addresses this gap by providing a literature review and a clear definition of PCC and outlines its main components as observed in real‐world practice.These components include daytime diagnostic and treatment procedures,in‐hospital and community‐based infusion centers,home‐based diagnostic and treatment services,smart healthcare solutions,and integration of traditional Chinese medicine.This document delves into the implementation of PCC and explores its potential benefits.
基金supported by the Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(No.XDB39040000)CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-003 and 2021-I2M-1-034)+2 种基金National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-017)Beijing Natural Science Foundation(No.7202158)National Natural Science Foundation of China(No.81971293).
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.
基金funded by the National Natural Science Foundation of China(No.32170788)National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-023)Beijing Natural Science Foundation(No.7232123).
文摘Secondary sclerosing cholangitis(SSC)is a chronic biliary disease characterized by inflammatory responses,fibrous occlusion,strictures,and progressive destruction of intrahepatic and/or extrahepatic bile ducts,which may lead to cholestasis and cirrhosis(1).Well-described causes of SSC include infectious,ischemic,toxic,immunologic,congenital disorders and so on(2,3).Here,we presented a rare case of sclerosing cholangitis secondary to acute severe biliary pancreatitis.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-040 to F.W.)the National Key Research and Development Program of China(2021YFA1102400 to F.W.,2019YFA0111700 to X.W.)the National Natural Science Foundation of China(82022001 and 81970103 to F.W.,82070111 to Y.Z.).
文摘Alternative polyadenylation(APA)is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites(PASs).APA is involved in lymphocyte activation;however,its role throughout the entire differentiation trajectory remains elusive.Here,we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells(HSPCs)to terminally differentiated lymphocytes.This analysis covered 19973 cells of 12 clusters from five lineages(B cells,CD4^(+)T cells,CD8^(+)T cells,natural killer cells,and plasmacytoid dendritic cells).A total of 2364 genes exhibited differential 3'-untranslated region(3'UTR)PAS usage,and 3021 genes displayed differential intronic cleavage during lymphoid differentiation.We observed a global trend of 3'UTR shortening during lymphoid differentiation.Nevertheless,specific events of both 3'UTR shortening and lengthening were also identified within each cluster.The APA patterns delineated three differentiation stages:HSPCs,precursor cells,and mature cells.Moreover,we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes(TCF7 and NFATC2IP),immune function-related genes(BCL2,CD5,CD28,GOLT1B,and TMEM59),and protein ubiquitination-related genes(UBE2G1,YPEL5,and SUMO3).These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.
基金supported by National High Level Hospital Clinical Research Funding[grant number 2022-PUMCH-B-022]CAMS Innovation Fund for Medical Sciences(CIFMS)from Chinese Academy of Medical Sciences[grant number 2021-I2M-1-062].
文摘Background:The optimal regimen of infliximab salvage in acute severe ulcerative colitis(ASUC)patients remains controversial.This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients,and to explore risk factors and concrete accelerated regimens for them.Methods:Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China.Outcomes including colectomy and clinical remission(Mayo score≤2 and every subscore≤1 at Day 14)rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjust-ment for potential confounders.The dose-response relationship was explored by plotting restricted cubic splines.Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes.A systematic re-view and meta-analysis was also performed.Results:A total of 76 patients were analysed:29 received standard and 47 received accelerated induction.The accelerated group had a higher 90-day colectomy rate(17.8%vs 0%,P=0.019)and lower clinical remission rate(27.7%vs 65.5%,P=0.001).After adjust-ing for propensity score and institution,there was no significant difference in colectomy or clinical remission rates(both P>0.05).Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days,with no improve-ment observed for increasing cumulative infliximab dosage within 28 days.Multivariate logistic regression analyses revealed C-reac-tive protein of>10 mg/L at infliximab initiation(odds ratio?5.00,95%confidence interval:1.27-24.34)as an independent risk factor for no clinical remission.Meta-analysis also revealed no significant difference in colectomy rates at 3 months(P=0.54).Conclusions:After adjusting for confounders,there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients.Early administration of an intensified dosage within 5 days may be beneficial.Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.
基金Capital's Funds for Health Improvement and Research,Grant/Award Number:2022-3-40714。
文摘Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supported by high-quality evidence.However,the TB indications and strategies are controversial.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,invited a panel of recognized urology experts in PCa to address these topics at the Panjiayuan Consensus Conference 2022.The conference results on prostate TB are presented herein.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences identified 10 key areas of prostate biopsy:(1)selection of imaging examination;(2)indications of TB;(3)transperineal and transrectal prostate biopsy;(4)TB pathways;(5)TB and SB;(6)three techniques of TB;(7)the number of TB cores needed for one lesion;(8)core number for SB;(9)free-hand TB;(10)future development of TB/prostate diagnosis.Thus,a panel of 25 recognized urologists and 2 radiologists from China were invited to attend this conference.The panel voted anonymously on 14 predetermined questions.Voting was based on the panelists'clinical practice and opinion,rather than high-level evidence.The voting outcomes were supported by the panel unequally,and details of the voting results were reported.The voting results can help clinicians to decide on biopsy timing and proper strategies,for which guidelines are sparse.We also focused on the future development of TB and SB,such as the combined pathway of TB and SB,techniques of TB,biopsy cores,free-hand TB,and prostate-specific membrane antigen positron emission tomography/computed tomography.
