BACKGROUND Esophageal cancer patients had the highest intensive care unit(ICU)admitted rate in cancer patients.But their prognosis and evaluation methods were rarely studied.AIM To depict the short-term mortality outc...BACKGROUND Esophageal cancer patients had the highest intensive care unit(ICU)admitted rate in cancer patients.But their prognosis and evaluation methods were rarely studied.AIM To depict the short-term mortality outcome and identify the potential prognostic factors of esophageal cancer patients admitted into ICU.METHODS A multicenter cross-sectional study was performed from May 10,2021 to July 10,2021 at ICU departments of 37 cancer specialized hospitals in China.Patients aged≥14 years with ICU duration≥24 hours were included.Clinical records of patients with primary esophageal cancer diagnosis were reviewed.Patients were separated into groups according to the 90 days survival.Characteristics between groups were compared.Single and multi-variate regression tests were applied to analyze the correlated factors of ICU outcomes.Predictive values of disease severity scores were assessed using receiver operating characteristic curve analysis.RESULTS Total 180 esophageal cancer patients were included.The 90 days mortality was 22.2%.Patients with mortality outcome showed differences from those survived mostly in disease severity and unplanned transfer from clinical ward.The current evaluation tools,including Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores had low accuracy in prediction of short-term death.ICU admitted esophageal cancer patients have poor prognosis,especially those with acute illness.CONCLUSION The prognostic tools for these patients need to be further optimized.展开更多
As the most prevalent post-transcriptional modification in transfer RNAs(tRNAs),methylation dynamically and reversibly regulates the biosynthesis and maturation of tRNAs,exerting direct impacts on the abundance and fu...As the most prevalent post-transcriptional modification in transfer RNAs(tRNAs),methylation dynamically and reversibly regulates the biosynthesis and maturation of tRNAs,exerting direct impacts on the abundance and functions of tRNAs responsible for the accurate translation of messenger RNAs(mRNAs).Consequently,aberrant tRNA methylation can potentially lead to the production of abnormally expressed proteins and the dysregulation of cellular homeostasis,underscoring the significance of tRNA methylation in tumorigenesis.Recent research has highlighted the aberrant expression of its catalytic regulators and proposed mechanisms through which tRNA methylation directly or indirectly influences tumor biological characteristics.This review provides a comprehensive summary of current research on tRNA methylation and its role in cellular function,aiming to deepen our understanding of the biological significance of tRNA methylation in tumorigenesis and to explore the potential of targeting tRNA methylation and tRNA-derived small RNAs(tsRNAs)for cancer therapy.展开更多
Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)...Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)breast cancer.We conducted a large-scale real-world study(RWS)in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.Methods:This multicenter,retrospective-prospective,non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol(E2)levels in premenopausal and perimenopausal patients with HR+breast cancer.Eligible patients were identified,and their demographic and clinical data were obtained from hospital medical records.The observation period was 28 weeks.Propensity score matching(PSM)ensured baseline comparability.The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4.Difference in proportions and 95%CI was calculated by Newcombe-Wilson score method.The non-inferiority margin was-10%.Subgroup and sensitivity analyses assessed result robustness.Results:From 1st January,2015 to 15th December,2023,15,629 patients from 16 hospitals nationwide were screened,with 1,060 eligible patients included in the full analysis set(3.6-mg group:678;10.8-mg group:382).Post-PSM,the primary endpoint was analyzed in 590 patients(295 in each group).At Week 12±4,the proportion of patients with E2 suppression was 99.1%(95%CI:96.9%-99.8%)for goserelin 10.8-mg and 95.3%(95%CI:91.0%-97.6%)for goserelin 3.6-mg.The difference was 3.8%(95%CI:0.6%-8.1%)with the lower limit of 95%CI greater than the non-inferiority margin.All subgroup analyses,including those based on age(≤45 or>45 years)and previous chemotherapy(yes/no),and all sensitivity analyses on the primary endpoint were consistent with the main analysis.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common cancers and CRC patients are among the most common intensive care unit(ICU)admitted cancer patients.However,their prognosis and evaluation methods are rarely ...BACKGROUND Colorectal cancer(CRC)is one of the most common cancers and CRC patients are among the most common intensive care unit(ICU)admitted cancer patients.However,their prognosis and evaluation methods are rarely studied.AIM To determine the short-term mortality outcome and identify the potential prognostic factors of CRC cancer patients admitted to the ICU.METHODS A multicenter cross-sectional study was performed from May 10,2021 to July 10,2021 at the ICU departments of 37 cancer specialized hospitals in China,and included patients aged≥14 years with ICU duration≥24 hours.Clinical records of patients with a primary CRC diagnosis were reviewed.Patients were separated into groups according to 90-day survival.Characteristics between groups were compared.Univariate and multivariate regression tests were used to analyze the correlated factors of ICU outcomes.Predictive values of disease severity scores were assessed using receiver operating characteristic curve analysis.RESULTS In total,189 CRC patients were included in the study.The 90-day mortality was 12.2%.Patients who died showed differences compared to patients who survived mostly in terms of disease severity and ICU complications.It appears that patients admitted to the ICU from a clinical ward due to emergencies may have a higher risk of mortality while surgical management was associated with better survival.In multivariate analysis,only chemotherapy,elective surgery and conventional oxygen therapy were identified as independently correlated with 90-day mortality.Sequential organ failure assessment and acute physiology and chronic health evaluation II scores had moderate accuracy in predicting short-term mortality.CONCLUSION ICU admitted CRC patients appear to have low short-term mortality which requires further confirmation in prospective studies.The prognostic tools for these patients need further optimization.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Objective: The purpose of this qualitative study was to describe the experiences of pain acceptance in Chinese cancer patients with chronic pain.Methods: Twelve hospitalized cancer patients with chronic pain participa...Objective: The purpose of this qualitative study was to describe the experiences of pain acceptance in Chinese cancer patients with chronic pain.Methods: Twelve hospitalized cancer patients with chronic pain participated in this qualitative descriptive study from August to November 2017.In-person semi-structured interviews were conducted,recorded,transcribed,and analyzed using Colaizzi's seven-step method.Results: The following four main themes and 15 subthemes emerged.Theme 1 (adaptation): pain is overwhelming and pain relief is a top priority,avoidance of pain-inducing factors,and resignation;theme 2 (emotional reactions to pain): feeling misunderstood,hopelessness,frustration,irritability,and concern for loved ones;theme 3 (functional limitations): daily life activities,social communication,and work;theme 4 (coping strategies): pharmacological therapies,behavioral strategies,social support strategies,and spiritual strategies.Conclusions: This study provides a description of cancer patients' experiences related to the need for pain acceptance.These findings provide insight into the essential role of pain acceptance and underline the need to apply acceptance-based cognitive behavioral interventions as adjunctive non-pharmacological alternatives for chronic cancer pain.展开更多
Clinical phototheranostic agents suffer from low absorption in near-infrared(NIR)region,decreasing singlet oxygen quantum yield(^(1)O_(2)QY)caused by aggregation in water,and low photothermal conversion efficiency(PCE...Clinical phototheranostic agents suffer from low absorption in near-infrared(NIR)region,decreasing singlet oxygen quantum yield(^(1)O_(2)QY)caused by aggregation in water,and low photothermal conversion efficiency(PCE),all of which are factors weakening their phototheranostic efficacy.Herein,we designed and synthesized a donor-acceptor-donor(D-A-D)structured boron-dipyrromethene derivative(B-2TPA)which exhibited NIR absorption and fluorescence.After being encapsulated in amphiphilic distearoyl phosphoethanolamine polyethyleneglycol 2000(DSPE-PEG-2000),the water-soluble B-2TPA nanoparticles(NPs)had increasing^(1)O_(2)QY(6.7%)due to the intermolecular aggregation-induced decrease in the energy gap between singlet and triplet excited states.Moreover,the quenched fluorescence and stable twisted intramolecular charge transfer in aggregates further increased the PCE of B-2TPA NPs to 60.1%.In vitro and in vivo studies confirmed that B-2TPA NPs could be used in NIR fluorescence and photoacoustic imagingguided synergistic photodynamic and photothermal therapy in tumor treatment.展开更多
BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However...BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.展开更多
Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising i...Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.展开更多
Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cance...Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.展开更多
Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expen...Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.展开更多
Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies ...Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).展开更多
Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC...Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.展开更多
Purpose:The major limitation of tumor microwave ablation(MWA)operation is the lack of predictability of the ablation zone before surgery.Operators rely on their individual experience to select a treatment plan,which i...Purpose:The major limitation of tumor microwave ablation(MWA)operation is the lack of predictability of the ablation zone before surgery.Operators rely on their individual experience to select a treatment plan,which is prone to either inadequate or excessive ablation.This paper aims to establish an ablation prediction model that guides MWA tumor surgical planning.Methods:An MWA process was first simulated by incorporating electromagnetic radiation equations,thermal equations,and optimized biological tissue parameters(dynamic dielectric and thermophysical parameters).The temperature distributions(the short/long diameters,and the total volume of the ablation zone)were then generated and verified by 60 cases ex vivo porcine liver experiments.Subsequently,a series of data were obtained from the simulated temperature distributions and to further fit the novel ablation coagulated area prediction model(ACAPM),thus rendering the ablation-dose table for the guiding surgical plan.The MWA clinical patient data and clinical devices suggested data were used to validate the accuracy and practicability of the established predicted model.Results:The 60 cases ex vivo porcine liver experiments demonstrated the accuracy of the simulated temperature distributions.Compared to traditional simulation methods,our approach reduces the long-diameter error of the ablation zone from 1.1 cm to 0.29 cm,achieving a 74%reduction in error.Further,the clinical data including the patients'operation results and devices provided values were consistent well with our predicated data,indicating the great potential of ACAPM to assist preoperative planning.展开更多
The first example of Nd@C_(3)N_(4)-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed,which allows for the synthesis of various 4-alkylated cyclic sulfonyl k...The first example of Nd@C_(3)N_(4)-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed,which allows for the synthesis of various 4-alkylated cyclic sulfonyl ketimines.In this process,chlorine functions as both a redox and hydrogen atom transfer catalyst.The synergism of the reversible Nd^(2+)/Nd^(3+)and Cl^(ˉ)/Cl˙redox pairs significantly enhances overall photocatalytic efficiency.The in vitro anticancer activity of 4-alkylated products was evaluated by using the CCK8assay against both human choroidal melanoma(MUM-2B)and lung cancer(A549)cell.Compound 3da showed approximately triple the potency of 5-fluorouracil.展开更多
BACKGROUND Visceral adipose tissue(VAT)plays a role in the pathogenesis of Crohn's disease(CD)and is associated with treatment outcomes following infliximab(IFX)therapy.We developed and validated the first delta-r...BACKGROUND Visceral adipose tissue(VAT)plays a role in the pathogenesis of Crohn's disease(CD)and is associated with treatment outcomes following infliximab(IFX)therapy.We developed and validated the first delta-radiomics model to quantify VAT heterogeneity as a predictive biomarker for IFX response in patients with CD.AIM To develop a longitudinal computed tomography(CT)-based delta-radiomics model of VAT for predicting secondary loss of response(SLR)in patients with CD.METHODS This retrospective study included 161 patients with CD who achieved clinical remission following IFX induction therapy between 2015 and 2023.All patients underwent CT enterography before IFX initiation and after completing induction therapy.VAT volume was delineated by two radiologists in consensus.Radiomics features were extracted from pre-treatment and post-induction CT images,and delta-radiomics features were calculated as follows:Delta features=Feature-post-Feature-pre.A radiomics model was constructed using logistic regression.Model performance was assessed using discrimination,calibration,and decision curve analyses.RESULTS Nine significant delta-radiomics features were used to develop the delta-radiomics model,yielding an area under the receiver operating characteristic curve(AUC)of 0.816(95%CI:0.737-0.896)in the training cohort and 0.750(95%CI:0.605-0.895)in the validation cohort.Multivariable logistic regression identified platelet count,Montreal behavior classification,and the VAT/subcutaneous adipose tissue volume ratio prior to treatment as independent risk factors for SLR.The combined model integrating clinical predictors and delta-radiomics features achieved superior predictive performance,with an AUC of 0.853(95%CI:0.786-0.921)in the training cohort and 0.812(95%CI:0.677-0.948)in the validation cohort.CONCLUSION We developed a predictive model based on longitudinal changes in VAT,demonstrating significant potential for identifying patients with CD at high risk of SLR to IFX therapy.展开更多
Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to deg...Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.展开更多
Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role ...Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.展开更多
Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO...Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.展开更多
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiolog...A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.展开更多
文摘BACKGROUND Esophageal cancer patients had the highest intensive care unit(ICU)admitted rate in cancer patients.But their prognosis and evaluation methods were rarely studied.AIM To depict the short-term mortality outcome and identify the potential prognostic factors of esophageal cancer patients admitted into ICU.METHODS A multicenter cross-sectional study was performed from May 10,2021 to July 10,2021 at ICU departments of 37 cancer specialized hospitals in China.Patients aged≥14 years with ICU duration≥24 hours were included.Clinical records of patients with primary esophageal cancer diagnosis were reviewed.Patients were separated into groups according to the 90 days survival.Characteristics between groups were compared.Single and multi-variate regression tests were applied to analyze the correlated factors of ICU outcomes.Predictive values of disease severity scores were assessed using receiver operating characteristic curve analysis.RESULTS Total 180 esophageal cancer patients were included.The 90 days mortality was 22.2%.Patients with mortality outcome showed differences from those survived mostly in disease severity and unplanned transfer from clinical ward.The current evaluation tools,including Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores had low accuracy in prediction of short-term death.ICU admitted esophageal cancer patients have poor prognosis,especially those with acute illness.CONCLUSION The prognostic tools for these patients need to be further optimized.
基金supported by grants from the National Natural Science Foundation of China(82273174 and 82072374)the Key Research and Development Program of Hunan Province(2023DK2001,2023SK2004,and 2023ZK1122).
文摘As the most prevalent post-transcriptional modification in transfer RNAs(tRNAs),methylation dynamically and reversibly regulates the biosynthesis and maturation of tRNAs,exerting direct impacts on the abundance and functions of tRNAs responsible for the accurate translation of messenger RNAs(mRNAs).Consequently,aberrant tRNA methylation can potentially lead to the production of abnormally expressed proteins and the dysregulation of cellular homeostasis,underscoring the significance of tRNA methylation in tumorigenesis.Recent research has highlighted the aberrant expression of its catalytic regulators and proposed mechanisms through which tRNA methylation directly or indirectly influences tumor biological characteristics.This review provides a comprehensive summary of current research on tRNA methylation and its role in cellular function,aiming to deepen our understanding of the biological significance of tRNA methylation in tumorigenesis and to explore the potential of targeting tRNA methylation and tRNA-derived small RNAs(tsRNAs)for cancer therapy.
文摘Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)breast cancer.We conducted a large-scale real-world study(RWS)in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.Methods:This multicenter,retrospective-prospective,non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol(E2)levels in premenopausal and perimenopausal patients with HR+breast cancer.Eligible patients were identified,and their demographic and clinical data were obtained from hospital medical records.The observation period was 28 weeks.Propensity score matching(PSM)ensured baseline comparability.The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4.Difference in proportions and 95%CI was calculated by Newcombe-Wilson score method.The non-inferiority margin was-10%.Subgroup and sensitivity analyses assessed result robustness.Results:From 1st January,2015 to 15th December,2023,15,629 patients from 16 hospitals nationwide were screened,with 1,060 eligible patients included in the full analysis set(3.6-mg group:678;10.8-mg group:382).Post-PSM,the primary endpoint was analyzed in 590 patients(295 in each group).At Week 12±4,the proportion of patients with E2 suppression was 99.1%(95%CI:96.9%-99.8%)for goserelin 10.8-mg and 95.3%(95%CI:91.0%-97.6%)for goserelin 3.6-mg.The difference was 3.8%(95%CI:0.6%-8.1%)with the lower limit of 95%CI greater than the non-inferiority margin.All subgroup analyses,including those based on age(≤45 or>45 years)and previous chemotherapy(yes/no),and all sensitivity analyses on the primary endpoint were consistent with the main analysis.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common cancers and CRC patients are among the most common intensive care unit(ICU)admitted cancer patients.However,their prognosis and evaluation methods are rarely studied.AIM To determine the short-term mortality outcome and identify the potential prognostic factors of CRC cancer patients admitted to the ICU.METHODS A multicenter cross-sectional study was performed from May 10,2021 to July 10,2021 at the ICU departments of 37 cancer specialized hospitals in China,and included patients aged≥14 years with ICU duration≥24 hours.Clinical records of patients with a primary CRC diagnosis were reviewed.Patients were separated into groups according to 90-day survival.Characteristics between groups were compared.Univariate and multivariate regression tests were used to analyze the correlated factors of ICU outcomes.Predictive values of disease severity scores were assessed using receiver operating characteristic curve analysis.RESULTS In total,189 CRC patients were included in the study.The 90-day mortality was 12.2%.Patients who died showed differences compared to patients who survived mostly in terms of disease severity and ICU complications.It appears that patients admitted to the ICU from a clinical ward due to emergencies may have a higher risk of mortality while surgical management was associated with better survival.In multivariate analysis,only chemotherapy,elective surgery and conventional oxygen therapy were identified as independently correlated with 90-day mortality.Sequential organ failure assessment and acute physiology and chronic health evaluation II scores had moderate accuracy in predicting short-term mortality.CONCLUSION ICU admitted CRC patients appear to have low short-term mortality which requires further confirmation in prospective studies.The prognostic tools for these patients need further optimization.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金This study was supported by the Hunan Provincial Natural Science Fund,China,grant number 2018JJ6110
文摘Objective: The purpose of this qualitative study was to describe the experiences of pain acceptance in Chinese cancer patients with chronic pain.Methods: Twelve hospitalized cancer patients with chronic pain participated in this qualitative descriptive study from August to November 2017.In-person semi-structured interviews were conducted,recorded,transcribed,and analyzed using Colaizzi's seven-step method.Results: The following four main themes and 15 subthemes emerged.Theme 1 (adaptation): pain is overwhelming and pain relief is a top priority,avoidance of pain-inducing factors,and resignation;theme 2 (emotional reactions to pain): feeling misunderstood,hopelessness,frustration,irritability,and concern for loved ones;theme 3 (functional limitations): daily life activities,social communication,and work;theme 4 (coping strategies): pharmacological therapies,behavioral strategies,social support strategies,and spiritual strategies.Conclusions: This study provides a description of cancer patients' experiences related to the need for pain acceptance.These findings provide insight into the essential role of pain acceptance and underline the need to apply acceptance-based cognitive behavioral interventions as adjunctive non-pharmacological alternatives for chronic cancer pain.
基金supported by National Key Research and Development Program of China(No.2022YFA1207600)National Natural Science Foundation of China(Nos.62175262,62375289)+2 种基金The Science and Technology Innovation Program of Hunan Province(No.2022RC1201)The Climb Plan of Hunan Cancer Hospital(No.ZX2021005)The Hunan Provincial Natural Science Foundation of China(No.2023JJ60464)。
文摘Clinical phototheranostic agents suffer from low absorption in near-infrared(NIR)region,decreasing singlet oxygen quantum yield(^(1)O_(2)QY)caused by aggregation in water,and low photothermal conversion efficiency(PCE),all of which are factors weakening their phototheranostic efficacy.Herein,we designed and synthesized a donor-acceptor-donor(D-A-D)structured boron-dipyrromethene derivative(B-2TPA)which exhibited NIR absorption and fluorescence.After being encapsulated in amphiphilic distearoyl phosphoethanolamine polyethyleneglycol 2000(DSPE-PEG-2000),the water-soluble B-2TPA nanoparticles(NPs)had increasing^(1)O_(2)QY(6.7%)due to the intermolecular aggregation-induced decrease in the energy gap between singlet and triplet excited states.Moreover,the quenched fluorescence and stable twisted intramolecular charge transfer in aggregates further increased the PCE of B-2TPA NPs to 60.1%.In vitro and in vivo studies confirmed that B-2TPA NPs could be used in NIR fluorescence and photoacoustic imagingguided synergistic photodynamic and photothermal therapy in tumor treatment.
基金the National Natural Science Foundation of Hunan Province,No.2023JJ60039Natural Science Foundation of Hunan Province National Health Commission,No.B202303027655+3 种基金Natural Science Foundation of Changsha Science and Technology Bureau,No.Kq2208150Wu Jieping Foundation of China,No.320.6750.2022-22-59,320.6750.2022-17-41Guangdong Association of Clinical Trials(GACT)/Chinese Thoracic Oncology Group(CTONG)and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer,No.2017B030314120.
文摘BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.
基金funded by the Optimization Study of Treatment Regimen and Clinical Practice in Ovarian Cancer(grant number:2016YFC1303702).
文摘Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.
基金the Hunan Lung Cancer Clinical Medical Research Center(Grant No.2023SK4024 to LW)the Hunan Science and Technology Innovation Program(Grant No.2021SK51121 to LW)the Hunan Cancer Hospital Climb plan(Grant No.ZX2020005-5 to LW)。
文摘Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.
基金co-supported by the National Natural Science Foundation of China (No. 81773521)CAMS Innovation Fund for Medical Sciences (No. 2017-I2M-1006, No. 2016-12M-2-004)+4 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2018RC330001)the National Key Projects of Research and Development of China (No. 2018 YFC1315000)China Scholarship Council (No. 201908110180)the Sanming Project of Medicine in Shenzhen (No. SZSM201911015)the Cancer Screening Program in Urban China funded by National Health Commission of People’s Republic of China
文摘Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.
基金funded by Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)National Natural Science Foundation of China(Grant No.82103677)National Science and Technology Major Projects of China(Grant No.2019ZX09732-001)。
文摘Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).
基金supported by the grants from the Beijing Hope Run Special Fund(#LC2012YF44)National Natural Science Foundation of China(No.81402740)+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education(No.20131106120014)The National Health and Family Planning Committee of P.R.China
文摘Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.
基金supported by the National Major Scientific Instruments and Equipment Development Project Funded by the National Natural Science Foundation of China(81827803)the Jiangsu Province Key Research and Development Program(Social Development)Project(BE2020705).
文摘Purpose:The major limitation of tumor microwave ablation(MWA)operation is the lack of predictability of the ablation zone before surgery.Operators rely on their individual experience to select a treatment plan,which is prone to either inadequate or excessive ablation.This paper aims to establish an ablation prediction model that guides MWA tumor surgical planning.Methods:An MWA process was first simulated by incorporating electromagnetic radiation equations,thermal equations,and optimized biological tissue parameters(dynamic dielectric and thermophysical parameters).The temperature distributions(the short/long diameters,and the total volume of the ablation zone)were then generated and verified by 60 cases ex vivo porcine liver experiments.Subsequently,a series of data were obtained from the simulated temperature distributions and to further fit the novel ablation coagulated area prediction model(ACAPM),thus rendering the ablation-dose table for the guiding surgical plan.The MWA clinical patient data and clinical devices suggested data were used to validate the accuracy and practicability of the established predicted model.Results:The 60 cases ex vivo porcine liver experiments demonstrated the accuracy of the simulated temperature distributions.Compared to traditional simulation methods,our approach reduces the long-diameter error of the ablation zone from 1.1 cm to 0.29 cm,achieving a 74%reduction in error.Further,the clinical data including the patients'operation results and devices provided values were consistent well with our predicated data,indicating the great potential of ACAPM to assist preoperative planning.
基金supported by grants from the Provincial Natural Science Foundation of Hunan(No.2023JJ60335)。
文摘The first example of Nd@C_(3)N_(4)-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed,which allows for the synthesis of various 4-alkylated cyclic sulfonyl ketimines.In this process,chlorine functions as both a redox and hydrogen atom transfer catalyst.The synergism of the reversible Nd^(2+)/Nd^(3+)and Cl^(ˉ)/Cl˙redox pairs significantly enhances overall photocatalytic efficiency.The in vitro anticancer activity of 4-alkylated products was evaluated by using the CCK8assay against both human choroidal melanoma(MUM-2B)and lung cancer(A549)cell.Compound 3da showed approximately triple the potency of 5-fluorouracil.
基金Supported by the National Natural Science Foundation of China,No.82372072 and No.82071986.
文摘BACKGROUND Visceral adipose tissue(VAT)plays a role in the pathogenesis of Crohn's disease(CD)and is associated with treatment outcomes following infliximab(IFX)therapy.We developed and validated the first delta-radiomics model to quantify VAT heterogeneity as a predictive biomarker for IFX response in patients with CD.AIM To develop a longitudinal computed tomography(CT)-based delta-radiomics model of VAT for predicting secondary loss of response(SLR)in patients with CD.METHODS This retrospective study included 161 patients with CD who achieved clinical remission following IFX induction therapy between 2015 and 2023.All patients underwent CT enterography before IFX initiation and after completing induction therapy.VAT volume was delineated by two radiologists in consensus.Radiomics features were extracted from pre-treatment and post-induction CT images,and delta-radiomics features were calculated as follows:Delta features=Feature-post-Feature-pre.A radiomics model was constructed using logistic regression.Model performance was assessed using discrimination,calibration,and decision curve analyses.RESULTS Nine significant delta-radiomics features were used to develop the delta-radiomics model,yielding an area under the receiver operating characteristic curve(AUC)of 0.816(95%CI:0.737-0.896)in the training cohort and 0.750(95%CI:0.605-0.895)in the validation cohort.Multivariable logistic regression identified platelet count,Montreal behavior classification,and the VAT/subcutaneous adipose tissue volume ratio prior to treatment as independent risk factors for SLR.The combined model integrating clinical predictors and delta-radiomics features achieved superior predictive performance,with an AUC of 0.853(95%CI:0.786-0.921)in the training cohort and 0.812(95%CI:0.677-0.948)in the validation cohort.CONCLUSION We developed a predictive model based on longitudinal changes in VAT,demonstrating significant potential for identifying patients with CD at high risk of SLR to IFX therapy.
基金supported by the National Natural Science Foundation of China(82103298)Basic Research Project of Science and Technology Cooperation in Qiandongnan Prefecture(No.2023-16).
文摘Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.
基金supported by the Key Research and Development Program of Hunan Province of China(2020SK2102)the Hunan Provincial Natural Science Foundation of China(2023JJ40420)+5 种基金the Changsha Municipal Natural Science Foundation(kq2208154)the Scientific Research Project of Hunan Provincial Health Commission(B202304088074)the Scientific Research Project of Hunan Provincial Health Commission(202203105045)the National Natural Science Foundation of China(82301435,82201484)the Hunan Provincial Natural Science Foundation of China(2024JJ4083)the Graduate Research and Innovation Project of Hunan Education Department(CX20220528).
文摘Background:Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra(SN).Activation of the neuroinflammatory response has a pivotal role in PD.Mesenchymal stem cells(MSCs)have emerged as a promising therapeutic approach for various nerve injuries,but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa(hOM)-MSCs on neural functional recovery in both PD models and patients,as well as the preventive effects on mouse models of PD.To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure,we employed single-cell RNA sequencing(scRNA-seq),assay for transposase accessible chromatin with high-throughput sequencing(ATAC-seq)combined with full-length transcriptome isoform-sequencing(ISO-seq),and functional assay.Furthermore,we present the findings from an initial cohort of patients enrolled in a phaseⅠfirstinhuman clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1(TGF-β1),secreted from hOM-MSCs,played a critical role in modulating mitochondrial function recovery in dopaminergic neurons.This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN,which are closely associated with neuroinflammatory responses.Mechanistically,exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B(ALK/PI3K/Akt)signaling pathway in microglia located in the SN of PD patients.Furthermore,intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD.Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD.Additionally,TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.
基金supported by the following funds:The National Natural Science Foundation of China(Nos.52275393,51935014,and 82072084)Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)+2 种基金The Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performancethe National Key Research and Development Program of China(No.2023YFB4605800)the Independent Exploration and Innovation Project of Central South University(No.1053320221707).
文摘Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.
基金supported by the National Natural Science Foundation of China,Nos.82171347,82371362the Natural Science Foundation of Hunan Province,No.2022JJ30971the Scientific Research Project of Hunan Provincial Health Commission of China,No.202204040024(all to GX).
文摘A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation.This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus,one of the most common neurological conditions worldwide.In this review,we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.Then,we outline the definition,classification,and biological role of non-coding RNAs.Subsequently,we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail.Specifically,we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus,including glymphatic pathways,neuroinflammatory processes,and neurological dysplasia,on the basis of the existing evidence.Lastly,we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
