Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Objective:To investigate the influencing factors and survival prognosis of thyroid function abnormality (TFA) induced by immune checkpoint inhibitors (ICI) in advanced lung cancer patients.Methods:Clinical data of advanced lung cancer patients who received ICI treatment in the Department of Oncology, the Beijing Chaoyang Hospital, Capital Medical University from January 1, 2019 to December 31, 2020 were retrospectively analyzed, and the patients were divided into TFA group and non-TFA group according to whether thyroid function was abnormal after ICI treatment. The baseline characteristics of the two groups were compared to evaluate the risk factors of TFA. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each risk factor to TFA. The progression-free survival time (PFS) of patients with different lung cancer pathological types and different TFA subtypes were analyzed by Kaplan-Meier method. The influencing factors of PFS in lung cancer patients were evaluated by COX regression analysis.Results:The ratio of neutrophil to lymphocyte (NLR) in the TFA group was lower than that in the non-TFA group [2.55(1.64, 3.46) vs 3.47(2.27, 5.30), P=0.014]. The ratio of lymphocyte to monocyte (LMR) was higher than that of the non-TFA group [4.25(2.89, 6.40) vs 3.12(2.03, 5.33), P=0.037]. The lactate dehydrogenase (LDH) was lower than that in the non-TFA group [173(146, 215) U/L vs 196(177, 234)U/L, P=0.023]. The objective response rate (ORR) in the TFA group was better than that in the non-TFA group [75.8%(25/33) vs 39.5%(34/86), P=0.002]. ROC curve analysis results showed that low NLR (≤3.37), high LMR (>3.79) and low LDH (≤173 U/L) had certain predictive value for TFA in advanced lung cancer patients treated by ICI (all P<0.05). Survival analysis showed that PFS in the TFA group was better than that in the non-TFA group in patients with overall lung cancer ( P<0.001) and various pathological types [squamous cell carcinoma ( P=0.010), adenocarcinoma ( P=0.001) and small cell lung cancer ( P=0.045)]. There was no significant difference in PFS among different TFA subtypes ( P>0.05). COX regression analysis showed that TFA [ HR(95% CI): 0.439(0.278, 0.693)] and therapeutic effect [ HR(95% CI): 3.401(2.143, 5.399)] was an independent influencing factor for PFS in advanced lung cancer patients treated by ICI. Patients who developed TFA ( P<0.001) and responded to treatment ( P<0.001) indicated a good prognosis. Conclusions:Lung cancer patients with low NLR, low LDH, high LMR and effective treatment are more likely to develop TFA. Lung cancer patients with TFA have a better immunotherapy response and a better survival prognosis.

Objective To explore the effects of aberrant O-glycosylation modifications induced by the knockout of Cosmc or T-synthase genes on the expression profiles of miRNAs in exosomes derived from colorectal cancer cells and to reveal the molecular mechanisms of O-glycosylation in the development of colorectal cancer and identify potential biomarkers for early diagnosis and treatment.Methods This research specifically targets the Cosmc or T-synthase genes in the human colorectal cancer cell line HCT116 to create stable cell lines exhibiting abnormal O-glycosylation with CRISPR/Cas-9 gene editing technology.Exosomes originating from these colorectal cancer cells were isolated and authenticated.A microarray chip equipped with primer sequences for 16 miRNAs closely associated with colorectal cancer was employed to assess the differential expression of miRNAs within these exosomes with fluorescent quantitative polymerase chain reaction(PCR).And then,a cohort of miRNAs that exhibited significant and consistent changes in expression levels across the exosomes from both cell lines was selected.These miRNAs were further validated independently with traditional fluorescent quantitative PCR.Subsequently,data from The Cancer Genome Atlas Program(TCGA)database containing patient information on colorectal cancer was harnessed.Employing R programming language,Gene Set Enrichment Analysis(GSEA)was conducted on the upregulated miRNA to investigate the downstream pathways significantly impacted and the malignant biological behaviors they may influence.Results The absence of either Cosmc or T-synthase genes results in the dysregulation of O-glycosylation in colorectal cancer cells,leading to the exposure of Tn antigens.This,in turn,affects the expression levels of specific miRNAs in exosomes derived from these cells.Specifically,the expression of hsa-miR-125b-1-3p was downregulated,while that of hsa-miR-218-5p was upregulated.Notably,hsa-miR-218-5p were found to be closely associated with the epithelial-mesenchymal transition(EMT)process in tumor cells,which is a key mechanism in cancer progression.Conclusion It elucidates that the aberrant O-glycosylation mediated by the knockout of Cosmc or T-synthase genes significantly influences the expression of certain miRNAs in exosomes from colorectal cancer cells,potentially affect the EMT process in colorectal cancer and thereby promoting distant metastasis.Given the inherent stability and detectability advantages of colorectal cancer-derived exosomes,the altered expression levels of miRNAs within these exosomes may serve as indicators of the stated of abnormal O-glycosylation in colorectal cancer.These findings suggest that exosomal miRNAs have potential as biomarkers for monitoring disease progression and therapeutic efficacy.Consequently,this could pave the way for more personalized diagnostic and treatment strategies tailored to individual colorectal cancer patients,enhancing the precision and effectiveness of clinical management.

Objective To explore the effects of aberrant O-glycosylation modifications induced by the knockout of Cosmc or T-synthase genes on the expression profiles of miRNAs in exosomes derived from colorectal cancer cells and to reveal the molecular mechanisms of O-glycosylation in the development of colorectal cancer and identify potential biomarkers for early diagnosis and treatment.Methods This research specifically targets the Cosmc or T-synthase genes in the human colorectal cancer cell line HCT116 to create stable cell lines exhibiting abnormal O-glycosylation with CRISPR/Cas-9 gene editing technology.Exosomes originating from these colorectal cancer cells were isolated and authenticated.A microarray chip equipped with primer sequences for 16 miRNAs closely associated with colorectal cancer was employed to assess the differential expression of miRNAs within these exosomes with fluorescent quantitative polymerase chain reaction(PCR).And then,a cohort of miRNAs that exhibited significant and consistent changes in expression levels across the exosomes from both cell lines was selected.These miRNAs were further validated independently with traditional fluorescent quantitative PCR.Subsequently,data from The Cancer Genome Atlas Program(TCGA)database containing patient information on colorectal cancer was harnessed.Employing R programming language,Gene Set Enrichment Analysis(GSEA)was conducted on the upregulated miRNA to investigate the downstream pathways significantly impacted and the malignant biological behaviors they may influence.Results The absence of either Cosmc or T-synthase genes results in the dysregulation of O-glycosylation in colorectal cancer cells,leading to the exposure of Tn antigens.This,in turn,affects the expression levels of specific miRNAs in exosomes derived from these cells.Specifically,the expression of hsa-miR-125b-1-3p was downregulated,while that of hsa-miR-218-5p was upregulated.Notably,hsa-miR-218-5p were found to be closely associated with the epithelial-mesenchymal transition(EMT)process in tumor cells,which is a key mechanism in cancer progression.Conclusion It elucidates that the aberrant O-glycosylation mediated by the knockout of Cosmc or T-synthase genes significantly influences the expression of certain miRNAs in exosomes from colorectal cancer cells,potentially affect the EMT process in colorectal cancer and thereby promoting distant metastasis.Given the inherent stability and detectability advantages of colorectal cancer-derived exosomes,the altered expression levels of miRNAs within these exosomes may serve as indicators of the stated of abnormal O-glycosylation in colorectal cancer.These findings suggest that exosomal miRNAs have potential as biomarkers for monitoring disease progression and therapeutic efficacy.Consequently,this could pave the way for more personalized diagnostic and treatment strategies tailored to individual colorectal cancer patients,enhancing the precision and effectiveness of clinical management.

Objective:To investigate the influencing factors and survival prognosis of thyroid function abnormality (TFA) induced by immune checkpoint inhibitors (ICI) in advanced lung cancer patients.Methods:Clinical data of advanced lung cancer patients who received ICI treatment in the Department of Oncology, the Beijing Chaoyang Hospital, Capital Medical University from January 1, 2019 to December 31, 2020 were retrospectively analyzed, and the patients were divided into TFA group and non-TFA group according to whether thyroid function was abnormal after ICI treatment. The baseline characteristics of the two groups were compared to evaluate the risk factors of TFA. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each risk factor to TFA. The progression-free survival time (PFS) of patients with different lung cancer pathological types and different TFA subtypes were analyzed by Kaplan-Meier method. The influencing factors of PFS in lung cancer patients were evaluated by COX regression analysis.Results:The ratio of neutrophil to lymphocyte (NLR) in the TFA group was lower than that in the non-TFA group [2.55(1.64, 3.46) vs 3.47(2.27, 5.30), P=0.014]. The ratio of lymphocyte to monocyte (LMR) was higher than that of the non-TFA group [4.25(2.89, 6.40) vs 3.12(2.03, 5.33), P=0.037]. The lactate dehydrogenase (LDH) was lower than that in the non-TFA group [173(146, 215) U/L vs 196(177, 234)U/L, P=0.023]. The objective response rate (ORR) in the TFA group was better than that in the non-TFA group [75.8%(25/33) vs 39.5%(34/86), P=0.002]. ROC curve analysis results showed that low NLR (≤3.37), high LMR (>3.79) and low LDH (≤173 U/L) had certain predictive value for TFA in advanced lung cancer patients treated by ICI (all P<0.05). Survival analysis showed that PFS in the TFA group was better than that in the non-TFA group in patients with overall lung cancer ( P<0.001) and various pathological types [squamous cell carcinoma ( P=0.010), adenocarcinoma ( P=0.001) and small cell lung cancer ( P=0.045)]. There was no significant difference in PFS among different TFA subtypes ( P>0.05). COX regression analysis showed that TFA [ HR(95% CI): 0.439(0.278, 0.693)] and therapeutic effect [ HR(95% CI): 3.401(2.143, 5.399)] was an independent influencing factor for PFS in advanced lung cancer patients treated by ICI. Patients who developed TFA ( P<0.001) and responded to treatment ( P<0.001) indicated a good prognosis. Conclusions:Lung cancer patients with low NLR, low LDH, high LMR and effective treatment are more likely to develop TFA. Lung cancer patients with TFA have a better immunotherapy response and a better survival prognosis.

Objective To observe the clinical effect of hypomethylating agents (HMAs) in the treatment of patients with intermediate- and high-risk myelodysplastic syndrome (MDS). Methods A retrospective study was conducted in 58 patients with intermediate-and high-risk MDS. The study group(25 patients) received azacitidine or decitabine for hypomethylating treatment, while the control group(33 patients) received routine symptomatic supportive treatment. The clinical efficacy, hematologic parameters, quality of life, and adverse events were observed and compared between the two groups. Results After treatment, the complete remission rate, objective response rate, and disease control rate were higher in the study group than in the control group, while the disease progression rate was lower (P < 0.05). The 1-year survival rate was 92.00% in the study group, which was higher than 75.76% in the control group, but the difference showed no statistically significant (P>0.05). After treatment, hemoglobin, white blood cell, and platelet levels were higher in both groups than before treatment, and were higher in the study group than in the control group (P < 0.05). The total incidence of adverse events was lower in the study group than that in the control group (P < 0.05). After treatment, the quality of life scores (physical function, cognitive function, emotional function, role function, and social function) were higher in the study group than those in the control group (P < 0.05). Conclusion HMAs treatment is superior to routine symptomatic supportive treatment in patients with intermediate-and high-risk MDS, and not only improves the quality of life but also has good safety.

The incidence and mortality rates of gastrointestinal tumors account for 26%and 35%of global malignant tumors,respectively,and continue to rise annually.Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors,as well as establishing precise molecularly targeted intervention strategies,have become critical scientific challenges in oncology research.Doublecortin-like kinase 1(DCLK1),a type II transmembrane protein harboring serine/threonine kinase domains,is well-recognized as a specific molecular marker for cancer stem cells.DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells,while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment.In recent years,tissue-resident memory T cells(TRM),characterized by their sustained tissue residency and potent antitumor immune efficacy,have emerged as a novel avenue for cancer immunotherapy.This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors,with a focus on its potential association with TRM cell functional activation,aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.

Objective:To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) .Methods:The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups.Results:The baseline parameters were balanced between the two groups ( P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant ( P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups ( P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% ( P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) ( P=0.198) . Conclusion:The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.

Objective To study the occurrence of tinnitus in elderly population in the Chengqiao area of Chongming Island,Shanghai,and explore the influencing factors,so as to provide reference for prevention and treatment of tinnitus in special areas.Methods A combination of questionnaire surveys,scale assessments,and pure-tone audiometry test were employed in this study.The study involved 6 358 elderly individuals who underwent health examinations at the Chengqiao Town Community Health Service Center in Chongming,Shanghai,from June 2019 to December 2021.Single and multiple factor analysis methods were used to analyze the impact of 13 factors,including gender,age,hearing status,sleep quality,anxiety and depression status,history of alcohol consumption,smoking history,history of noise exposure,history of ototoxic drug use,hypertension,diabetes,hyperlipidemia,and coronary heart disease on tinnitus in the elderly population.Results ① Among the 6 358 elderly cases,there were 2 110 cases with tinnitus,and the incidence rate of tinnitus was 33.2％(2 110/6 358),and 1 712 cases were chronic tinnitus(81.1％),and 1 156 cases were bilateral tinnitus(54.8％).According to THI score,there were 1 012 patients(48％)were mild tinnitus,and 2 030 patients(96.2％)with average hearing threshold ≥25 dB HL.② Univariate analysis showed that age,hearing status,sleep quality,anxiety and depression,history of noise expo-sure,history of ototoxic drugs,and history of hypertension were related to the occurrence of tinnitus.Further bina-ry logistic regression analysis showed that increasing age(OR=1.10,95％CI 1.09～1.11,P＜0.001),hearing loss(OR=5.56,95％CI 4.31～7.18,P＜0.001),sleep disorder(OR=3.32,95％CI 2.82～3.91,P＜0.001),anxiety depression(OR=2.02,95％CI 1.71～2.39,P＜0.001),history of noise exposure(OR=3.67,95％CI 3.20～4.21,P＜0.001),history of ototoxic drugs(OR=2.20,95％CI 1.84～2.64,P＜0.001)and history of hy-pertension(OR=1.73,95％CI 1.53～1.95,P＜0.001)increased the risk of tinnitus.Conclusion The incidence of tinnitus in the elderly people in the Chengqiao area of Chongming is relatively high.Factors such as age,hearing status,sleep quality,anxiety and depression,history of noise exposure,history of ototoxic drugs,and history of hypertension are risk factors for the occurrence of tinnitus in the elderly population.