Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

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 Pulmonary oxygen poisoning resulting from hyperbaric oxygen,frequently occurs in specialized operations,without any current effective prevention or treatment measures.To elucidate the impact and mechanism of neostigmine(NEO)in combination with anisodamine(ANI)(neoscopolamine)on pulmonary oxygen toxicity.Methods The animal model of pulmonary oxygen poisoning was established.C57BL/6 mice were exposed to 2.5 ATA 99.9%oxygen for 6 h.The control group mice were injected with normal saline ip,while the treatment group mice received injections of ANI(25 mg/kg,ip)and NEO(50 μg/kg,ip).Lung tissues were collected and stained with HE to observe any pathological injuries after exposure.Evans blue stain was utilized to identify lung permeability,wet/dry lung ratio,and protein concentration in the bronchoalveolar lavage fluid(BALF)to assess the lung injury's severity.The modifications in inflammatory factors,oxidative stress indicators,and iron content in lung tissue were assessed.Results The results showed that the 2.5 ATA 99.9%oxygen-exposed group experienced a significant worsening of lung injury,as well as increased lung permeability,lung wet/dry ratio,and protein content in alveolar lavage fluid when compared to the control group.Moreover,mRNA levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,and IFN-γ in the lung tissue of the model group were significantly elevated,while the levels of anti-inflammatory cytokines IL-4 and TGF-β were significantly reduced.The oxidative index MDA also significantly increased,while the antioxidant index GSH significantly decreased.Additionally,the expression of GPX4,a marker of ferroptosis,increased with an increase in iron content.Neoscopolamine treatment successfully reversed those effects.Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning.Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway,thereby reducing the content of free iron in lung tissue and finally inhibiting cell ferroptosis.

Objective:To discuss the clinical characteristics of autosomal recessive spinocerebellar ataxia type 16 patients caused by STUB1 gene mutation, in order to improve the clinical doctors′ understanding of the disease. Methods:The clinical manifestations, auxiliary examinations and genetic testing of 1 autosomal recessive spinocerebellar ataxia type 16 patient caused by STUB1 gene variants diagnosed in Qilu Hospital of Shandong University in May 2022 were collected, and the relevant literature was reviewed to summarize the clinical and genetic characteristics of this type of disease. Results:The proband was a 35-year-old male presenting with unsteady walk and dysarthria. Magnetic resonance imaging showed cerebellar atrophy. Next generation sequencing revealed compound heterozygous c.322dupG (p.Glu108Glyfs *4) and c.433A>C (p.Lys145Gln) variants in the STUB1 gene (according to the transcript NM_005861.4), and the c.322dupG (p.Glu108Glyfs *4) variant was a novel variant. Pedigree verification revealed the 2 variants were respectively inherited from the proband′s healthy parents. A total of 12 foreign literatures reported 32 autosomal recessive spinocerebellar ataxia type 16 patients. The main clinical manifestations were ataxia, dysarthria and tendon hyperreflexia. Besides, nystagmus, spasticity, action tremors, and myoclonus can be present. Magnetic resonance imaging predominantly showed cerebellar atrophy. Conclusions:The patient with autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant is rare in China. The main clinical manifestation is cerebellar ataxia, and brain imaging reveals remarkable cerebellar atrophy. Genetic testing is helpful for definite diagnosis.

Objective To investigate the effects of doublecortin-like kinase 1(DCLK1)on the malignant biological behaviors,such as proliferation,migration,and invasion,of A549 cell line and their corresponding mechanisms.Methods DCLK1-overexpressing A549 cell lines were established through lentiviral infection,and DCLK1 expression was validated by using RT-PCR and Western blot analysis.Proliferation ability was assessed with CCK-8 and plate cloning assays,and migration and invasion abilities were examined with Transwell assays.The pathway regulated by DCLK1 in lung adenocarcinoma was analyzed on the basis of the TCGA lung adenocarcinoma cohort with pathway enrichment analysis and verified through Western blot analysis.Results DCLK1 overexpression in A549 cells promoted cell proliferation,migration,and invasion.The inhibition of the FAK/PI3K/AKT/mTOR signaling pathway impaired the DCLK1-mediated malignant behavior of A549 cells.Conclusion DCLK1 promotes the malignant behavior of A549 cells through the activation of the FAK/PI3K/AKT/mTOR signaling pathway.

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.