Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL...Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods: The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30) was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, and pancreatic cancer). A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results: The average QoL score was 50.4 ± 10.8. The tumor type, age, sex, and TNM stage al had an impact on QoL ratings. Colorectal cancer patients had a better total QoL score(49.3 ± 10.3) and scores in the domains of functioning, with milder symptoms, except for diarrhea. Patients with biliary tract cancer(54.2 ± 12.3) and pancreatic cancer(54.2 ± 12.3) reported a poorer QoL, significant functional impairment, and more pronounced symptoms. Patients with esophageal cancer experienced the most severe financial difficulties(35.2 ± 27.5). Patients aged ≥65 years, women, and those with TNM stage Ⅲ/Ⅳ reported lower QoL. In addition, the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors, and based on ethnicity, educational level, occupation, treatment(s) received, and place of residence.Conclusions: There is a need to focus on elderly individuals, those with low educational levels, and patients with progressive malignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.展开更多
Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment opt...Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment options.Dysregulated microRNAs(miRNAs)are involved in various cellular processes in TNBC.Moreover,variations in the miRNA levels in TNBC may act as a dependable indicator for predicting the effectiveness and specificity of treatments.Currently,the application of miRNAs for breast cancer therapy is primarily in the preclinical stage,with a focus on identifying highly specific and sensitive miRNAs that could offer new possibilities for early diagnosis,clinical treat-ment,and prognostic monitoring of TNBC.展开更多
AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This...AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.展开更多
DNA2,a multifunctional enzyme with structure-specific nuclease,5'-to-3'helicase,and DNA-dependent ATPase activities,plays a pivotal role in the cellular response to DNA damage.However,its involvement in cerebr...DNA2,a multifunctional enzyme with structure-specific nuclease,5'-to-3'helicase,and DNA-dependent ATPase activities,plays a pivotal role in the cellular response to DNA damage.However,its involvement in cerebral ischemia/reperfusion(I/R)injury remains to be elucidated.This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout(cKO)mice(Nestin-Cre)subjected to middle cerebral artery occlusion(MCAO),an established model of cerebral I/R.Results demonstrated a gradual up-regulation of DNA2 expression,peaking at 72 h post-MCAO.Notably,DNA2 cKO mice exhibited more pronounced brain injury,neurological deficits,and neuronal apoptosis within the penumbra following MCAO.Additionally,DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation(OGD/R)cell culture model,and DNA2 knockdown(KD)exacerbated neuronal apoptosis and oxidative stress.Transcriptome analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of Homer1 in DNA2 cKO mice.Furthermore,in vitro experiments demonstrated that overexpression of Homer1a ameliorated DNA2 KD-induced neuronal apoptosis.Collectively,these findings demonstrate that DNA2 deficiency exacerbates cerebral I/R injury through the down-regulation of Homer1a,highlighting a novel regulatory axis in ischemic neuroprotection.展开更多
BACKGROUND Primary renal synovial sarcoma(PRSS)is extremely rare in clinical practice,and most cases are associated with SYT-SSX gene fusion.The PRSS with specific MDM2 gene amplification has not been reported so far....BACKGROUND Primary renal synovial sarcoma(PRSS)is extremely rare in clinical practice,and most cases are associated with SYT-SSX gene fusion.The PRSS with specific MDM2 gene amplification has not been reported so far.Therefore,there is no practical experience regarding the clinical,pathological features and diagnosis and treatment plans for patients of this type.This article reports a case of PRSS with specific MDM2 gene amplification.CASE SUMMARY The patient was preoperatively diagnosed with a malignant tumor of the left kidney(with a high probability of clear cell carcinoma).During the operation,a radical left nephrectomy was performed.The postoperative pathological examination report confirmed synovial sarcoma,and the gene test suggested PRSS with specific MDM2 gene amplification.Forty-eight days after the operation,the patient presented with"abdominal distension and diarrhea"and was found to have a huge metastatic tumor in the original left renal area.The patient died clinically 17 hours after admission due to"multiple organ failure".CONCLUSION PRSS with MDM2 gene amplification has a poorer prognosis,a higher degree of malignancy,and a faster progression,and clinicians need to be highly vigilant.展开更多
BACKGROUND Diabetic retinopathy(DR)is one of the major eye diseases contributing to blindness worldwide.Endoplasmic reticulum(ER)stress in retinal cells is a key factor leading to retinal inflammation and vascular lea...BACKGROUND Diabetic retinopathy(DR)is one of the major eye diseases contributing to blindness worldwide.Endoplasmic reticulum(ER)stress in retinal cells is a key factor leading to retinal inflammation and vascular leakage in DR,but its mechanism is still unclear.AIM To investigate the potential mechanism of LEF1 and related RNAs in DR.METHODS ARPE-19 cells were exposed to high levels of glucose for 24 hours to simulate a diabetic environment.Intraperitoneally injected streptozotocin was used to induce the rat model of DR.The expression levels of genes and related proteins were measured by RT-qPCR and Western blotting;lnc-MGC and miR-495-3p were detected by fluorescent in situ hybridization;CCK-8 and TUNEL assays were used to detect cell viability and apoptosis;enzyme-linked immunosorbent assay was used to detect inflammatory factors;dual-luciferase gene assays were used to verify the targeting relationship;and the retina was observed by HE staining.RESULTS LEF1 and lnc-MGC have binding sites,and lnc-MGC can regulate the miR-495-3p/GRP78 molecular axis.In high glucose-treated cells,inflammation was aggravated,the intracellular reactive oxygen species concentration was increased,cell viability was reduced,apoptosis was increased,the ER response was intensified,and ferroptosis was increased.As an ER molecular chaperone,GRP78 regulates the ER and ferroptosis under the targeting of miR-495-3p,whereas inhibiting LEF1 can further downregulate the expression of lnc-MGC,increase the level of miR-495-3p,and sequentially regulate the level of GRP78 to alleviate the occurrence and development of DR.Animal experiments indicated that the knockdown of LEF1 can affect the lnc-MGC/miR-495-3p/GRP78 signaling axis to restrain the progression of DR.CONCLUSION LEF1 knockdown can regulate the miR-495-3p/GRP78 molecular axis through lnc-MGC,which affects ER stress and restrains the progression of DR and ferroptosis in retinal pigment epithelial cells.展开更多
BACKGROUND The role of cerebral microvascular dysfunction in early cognitive impairment and dementia has become increasingly recognized.Furthermore,pathological changes in both Alzheimer’s disease and vascular dement...BACKGROUND The role of cerebral microvascular dysfunction in early cognitive impairment and dementia has become increasingly recognized.Furthermore,pathological changes in both Alzheimer’s disease and vascular dementia are almost always associated with cerebral hemodynamic deficits.AIM To investigate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)assessment of the blood-brain barrier(BBB)in combination with relevant plasma biomarkers for mild cognitive impairment(MCI).METHODS This study selected 50 patients with non-amnestic MCI(na-MCI group),52 patients with amnestic MCI(a-MCI group),and 55 healthy elderly controls(control group).The Chinese version of the Montreal cognitive assessment(MoCA),auditory verbal learning test(AVLT),Hamilton anxiety/depression scale(HAMA/HAMD),and activity of daily living(ADL)scales were used to analyze the characteristics of mental and behavioral symptoms of patients with MCI.The DCE-MRI technique was used to assess the contrast enhancement kinetics.The Patlak model was utilized to analyze the BBB permeability(volume transfer constants).Further,fasting blood was was used to quantify plasma homocysteine(Hcy),β-amyloid protein(Aβ)40,Aβ42,human phosphorylated tau-181 protein(p-tau181),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),and plasminogen activator inhibitor-1(PAI-1)levels,as well as serum neurofilament light chain(NFL)and glial fibrillary acidic protein(GFAP)concentrations.RESULTS The na-MCI and a-MCI groups demonstrated significantly lower MoCA and AVLT-Huashan version scores,and statistically higher HAMA,HAMD,and ADL scores compared to the control group.Moreover,the a-MCI group showed notably higher HAMA,HAMD,and ADL scores compared to the na-MCI group.Cranial MRI results revealed significant disparities in cerebral blood flow in the left and right frontal lobes,temporal lobes,hippocampi,cuneus,precuneus,parietal lobes,basal ganglia,and occipital lobes between the a-MCI and na-MCI groups.Compared to healthy controls,patients with MCI demonstrated a smaller amplitude of hippocampal contrast enhancement kinetics and a slower decay rate,indicating smaller vascular volume and increased BBB permeability.Further,Hcy,p-tau181,ICAM-1,VCAM-1,PAI-1,and NFL levels were substantially higher in the a-MCI group than in the na-MCI group,whereas the Aβ42 level was significantly lower.We did not observe any significant differences in Aβ40 and GFAP levels.CONCLUSION Patients with MCI may have experienced cerebrovascular system changes in the hippocampal region.Disorders associated with changes in cerebral blood supply may begin before pathophysiological changes are visible by imaging,which provides references for the assessment and treatment of patients with cognitive disorders.Further,DCE-MRI provides a noninvasive approach to diagnose subtle BBB leakage associated with cerebrovascular pathology.展开更多
BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare.Most reported cases of metastatic invasive mole are diagnosed after surgery,and lack rich illustrations,wh...BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare.Most reported cases of metastatic invasive mole are diagnosed after surgery,and lack rich illustrations,which leads to insufficient understanding by clinicians,misdiagnosis,and unnecessary surgeries.CASE SUMMARY A 22-year-old female patient presented with bloody stool and elevated human chorionic gonadotropin.The transvaginal gynecological ultrasound ruled out pregnancy.Upper gastrointestinal endoscopy and colonoscopy were performed,but no bleeding focus was detected.The contrast-enhanced computed tomography was unremarkable.The capsule endoscopy suggested jejunal protuberant lesions with dark red blood clots.Therefore,oral single-balloon enteroscopy was performed,and two connected protuberant lesions were detected,with blood clot traces and local ulceration.The enteroscopic biopsy revealed trophoblastic cells with a probable diagnosis of trophoblastic tumor.The patient underwent surgical resection of the diseased jejunum.Intraoperative endoscopy was performed,and the findings were the same as those of the small intestine endoscopy.The postoperative pathology confirmed the preoperative diagnosis of invasive mole.CONCLUSION In non-pregnant women with elevated human chorionic gonadotropin and gastrointestinal bleeding,metastatic trophoblastic neoplasia should be considered.展开更多
Objective:To evaluate the value of real-time two-dimensional shear wave elastography(SWE)in predicting liver parenchymal stiffness in non-alcoholic fatty liver disease(NAFLD).Methods:A total of 200 NAFLD patients(70 i...Objective:To evaluate the value of real-time two-dimensional shear wave elastography(SWE)in predicting liver parenchymal stiffness in non-alcoholic fatty liver disease(NAFLD).Methods:A total of 200 NAFLD patients(70 in the mild group,70 in the moderate group,and 60 in the severe group)and 60 healthy individuals(control group)who visited the hospital from December 2023 to December 2024 underwent real-time two-dimensional SWE examinations.Results:Except for high-density lipoprotein,comparisons of body mass index and biochemical indicators showed that the severe group>moderate group>mild group>control group,with P<0.05.Comparisons of liver stiffness values also showed that the severe group>moderate group>mild group>control group,with P<0.05.Pearson correlation analysis revealed a positive correlation between liver stiffness values and body mass index,triglycerides,total cholesterol,low-density lipoprotein,fasting blood glucose,and glycosylated hemoglobin.Analysis of the ROC curve indicated that the AUC,standard deviation,and P-value for liver stiffness values were 0.901,0.025,and 0.01,respectively,suggesting that liver stiffness values can predict the severity of NAFLD.Conclusion:The real-time two-dimensional shear wave elastography(SWE)technique for diagnosing NAFLD can differentiate between NAFLD patients and healthy individuals,as well as determine liver parenchymal stiffness,thereby assisting physicians in quantifying the degree of fatty liver.展开更多
Background:To investigate adverse event(AE)signals associated with six proton pump inhibitors(PPIs),enhance drug labeling information,and provide guidance for their safe clinical use.Methods:Adverse reaction data for ...Background:To investigate adverse event(AE)signals associated with six proton pump inhibitors(PPIs),enhance drug labeling information,and provide guidance for their safe clinical use.Methods:Adverse reaction data for musculoskeletal and connective tissue disorders related to six PPI formulations—omeprazole,pantoprazole,lansoprazole,esomeprazole,rabeprazole,and dexlansoprazole—from Q12004 to Q42023 were collected from the FDA Adverse Event Reporting System(FAERS).Signal detection was performed using the Reporting Odds Ratio(ROR),Proportional Reporting Ratio(PRR),Bayesian Confidence Propagation Neural Network(BCPNN),and Empirical Bayesian Geometric Mean(EBGM).Data processing and statistical analysis were conducted using R Studio 4.40.Results:A total of 6,635,3,853,1,792,15,731,483,and 534 adverse events were identified for the six PPIs,respectively.The four algorithms(ROR,PRR,BCPNN,and EBGM)generated 17,19,8,27,5,and 2 positive signals.Notably,signals for renal osteodystrophy and osteoporosis were more frequent,with stronger signals for lumbar flexion syndrome and renal osteodystrophy.Conclusion:Patients with chronic kidney disease,a high risk of osteoporosis and fractures,or those using statins should select PPIs with a lower risk of adverse musculoskeletal and connective tissue reactions to minimize these adverse effects and ensure standardized clinical use of PPIs.展开更多
BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with gluco...BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with glucocorticoid(GCs)shock be-fore surgery,followed by surgical treatment,all of whom achieved good results.The effect of GCs on thymomas is related mainly to the action on GC receptors in thymic lymphocytes and epithelial cells.GC receptor expression has been asso-ciated with a better prognosis in patients with thymomas,including those with surgically removed thymomas.CASE SUMMARY We report a case of a patient with thymoma who had a significant response to preoperative low-dose GC therapy.A mediastinal tumor was detected in the patient via computerized tomography upon admission.The tumor was initially suspected to be a thymic tumor,but lymphoma could not be ruled out.The tumor shrank significantly after low-dose(5 mg/day)GC therapy.Thoracoscopic thy-moma resection was performed after puncture pathology was confirmed.The patient recovered well after the operation and is currently performing well with no recurrence of the tumor.CONCLUSION This case highlights that low-dose GCs are effective in the treatment of thymomas,and we believe that GCs should be applied more frequently and studied more thoroughly in the treatment of thymomas.展开更多
BACKGROUND Gastrointestinal dual-contrast ultrasonography(DCUS)is characterized by its high resolution,sensitivity,and specificity.AIM To determine the accuracy of DCUS in predicting lymph node metastasis in middle-ag...BACKGROUND Gastrointestinal dual-contrast ultrasonography(DCUS)is characterized by its high resolution,sensitivity,and specificity.AIM To determine the accuracy of DCUS in predicting lymph node metastasis in middle-aged and elderly patients with gastric cancer(GC).METHODS A total of 100 middle-aged and elderly patients with GC admitted to the Fourth Affiliated Hospital of Soochow University(Dushu Lake Hospital,Suzhou,China)between April 2022 and April 2024 were selected.The baseline data and lymph node metastasis status were collected.DCUS combined with intravenous contrast technology was used to calculate the enhancement time(ET),time to peak(TTP),and slope of the ascending branch wash-in rate(WIR).These indicators were used in assessing lymph node metastasis in patients with GC.RESULTS Among 100 middle-aged and elderly patients with GC,35(35.00%)had lymph node metastases.GC patients with lymph node metastasis had a higher propor-tion of stage II TNM classification and higher WIR values than those without lymph node metastasis.The ET and TTP values were lower in patients with lymph node metastases,and all differences were statistically significant(P<0.05).The area under the curve values for ET,TTP,WIR,and combined diagnosis of GC lymph node metastasis using DCUS were all>0.7.Optimal assessment was achieved when the cutoff values for ET,TTP,and WIR were set at 16.32 seconds,10.67 seconds,and 7.02,res-pectively.CONCLUSION DCUS-mediated assessment of ET,TTP,and WIR can effectively predict and evaluate lymph node metastasis status in patients with GC,with higher sensitivity when used in combination.展开更多
BACKGROUND Accurate preoperative differentiation of benign and malignant thyroid nodules is critical for optimal patient management.However,conventional imaging modalities present inherent diagnostic limitations.AIM T...BACKGROUND Accurate preoperative differentiation of benign and malignant thyroid nodules is critical for optimal patient management.However,conventional imaging modalities present inherent diagnostic limitations.AIM To develop a non-contrast computed tomography-based machine learning model integrating radiomics and clinical features for preoperative thyroid nodule classification.METHODS This multicenter retrospective study enrolled 272 patients with thyroid nodules(376 thyroid lobes)from center A(May 2021-April 2024),using histopathological findings as the reference standard.The dataset was stratified into a training cohort(264 lobes)and an internal validation cohort(112 lobes).Additional prospective temporal(97 lobes,May-August 2024,center A)and external multicenter(81 lobes,center B)test cohorts were incorporated to enhance generalizability.Thyroid lobes were segmented along the isthmus midline,with segmentation reliability confirmed by an intraclass correlation coefficient(≥0.80).Radiomics feature extraction was performed using Pearson correlation analysis followed by least absolute shrinkage and selection operator regression with 10-fold cross-validation.Seven machine learning algorithms were systematically evaluated,with model performance quantified through the area under the receiver operating characteristic curve(AUC),Brier score,decision curve analysis,and DeLong test for comparison with radiologists interpretations.Model interpretability was elucidated using SHapley Additive exPlanations(SHAP).RESULTS The extreme gradient boosting model demonstrated robust diagnostic performance across all datasets,achieving AUCs of 0.899[95%confidence interval(CI):0.845-0.932]in the training cohort,0.803(95%CI:0.715-0.890)in internal validation,0.855(95%CI:0.775-0.935)in temporal testing,and 0.802(95%CI:0.664-0.939)in external testing.These results were significantly superior to radiologists assessments(AUCs:0.596,0.529,0.558,and 0.538,respectively;P<0.001 by DeLong test).SHAP analysis identified radiomic score,age,tumor size stratification,calcification status,and cystic components as key predictive features.The model exhibited excellent calibration(Brier scores:0.125-0.144)and provided significant clinical net benefit at decision thresholds exceeding 20%,as evidenced by decision curve analysis.CONCLUSION The non-contrast computed tomography-based radiomics-clinical fusion model enables robust preoperative thyroid nodule classification,with SHAP-driven interpretability enhancing its clinical applicability for personalized decision-making.展开更多
BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteo...BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.展开更多
Epilepsy is a devastating neurological condition that affects over 70 million people worldwide.Apart from idiopathic epilepsy,numerous diseases have been reported to cause secondary epilepsy.Polyphenols,ubiquitously e...Epilepsy is a devastating neurological condition that affects over 70 million people worldwide.Apart from idiopathic epilepsy,numerous diseases have been reported to cause secondary epilepsy.Polyphenols,ubiquitously existing in fruits and vegetables,has become a promising neuroprotective candidate against multiple neurological abnormalities due to its interplay with gut microbiome composed of the bacterial population in gastrointestinal system.This bioactive compound is also being tested for the management of epileptogenesis.However,there is still insufficient evidence from mechanistic studies to demonstrate the causal relationship between anti-epileptic effect of polyphenols and microbial alteration.In this review,we provide the brief overview of epilepsy,polyphenols and gut microbiota.We then analysis the association of polyphenols and gut microbiota particularly in the epilepsy and symptomatic seizures-induced by epilepsy related disorders.We also discuss the possibility for the combined application with probiotics to improve the bioavailability and bioaccessibility of polyphenols for expanding its anti-epileptic function.We finally summarize the therapeutic potential of anti-seizure polyphenols through affecting gut microbiome,and propose that the anti-epileptic effect of polyphenols may be tightly relevant to intestinal bacterial flora for overcoming epilepsy and its comorbidities simultaneously.Therefore,the dietary polyphenols targeting specific bacteria may achieve the outcome of‘one stone,two birds’.展开更多
BACKGROUND Right ventricular hypertrophy(RVH)occurs because of volume or pressure overload within the right ventricular(RV)system.RVH is associated with complex pathological changes,including myocardial cell injury,ap...BACKGROUND Right ventricular hypertrophy(RVH)occurs because of volume or pressure overload within the right ventricular(RV)system.RVH is associated with complex pathological changes,including myocardial cell injury,apoptosis,myocardial fibrosis,neuroendocrine disturbances,and abnormal water and liquid metabolism.Ferroptosis,a novel type of iron-dependent cell death characterized by lipid peroxide accumulation,is an important mechanism of cardiomyocyte death.However,the role of ferroptosis in RVH has rarely been studied.We hypothesize that hydrogen(H_(2)),an experimental medical gas with superior distri-bution characteristics,inhibits ferroptosis.AIM To explore the protective effect of H_(2) on RVH and the mechanism by which H_(2) regulates ferroptosis.METHODS An in vivo RVH rat model was induced by monocrotaline(MCT)in 30 male Sprague-Dawley rats.An H9C2 cell model was treated with angiotensin II to simulate pressure overload in the RV system in vitro.H_(2) was administered to rats by inhalation(2%for 3 hours daily for 21 days)and added to the cell culture medium.The Nrf2 inhibitor ML385(1μM)was used to investigate anti-ferroptotic mechanisms.RESULTS In MCT-treated rats,H_(2) inhalation decreased RVH;the RV wall thickness decreased from 3.5±0.3 mm to 2.8±0.2 mm(P<0.05)and the RV ejection fraction increased from 45±3%to 52±4%(P<0.05).In H9C2 cells,H_(2) alleviated hypertrophy.H_(2) inhibited ferroptosis by modulating the iron content,oxidative stress,and ferroptosis-related proteins,thereby restoring the Nrf2/HO-1 signaling pathway.CONCLUSION H_(2) retards RVH by inhibiting ferroptosis via Nrf2/HO-1 restoration,suggesting a new treatment strategy.展开更多
Background:Circular RNAs play an important role in regulating lung adenocarcinoma(LUAD).Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD.However,the biological mechanism of circ_0015...Background:Circular RNAs play an important role in regulating lung adenocarcinoma(LUAD).Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD.However,the biological mechanism of circ_0015278 in LUAD has not been fully clarified,especially in ferroptosis.Materials and Methods:Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278,subsequently confirmed by luciferase reporter assays.The impact of Circ_0015278 on cell proliferation,migration,invasion,and ferroptosis was investigated through a loss-of-function experiment.A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth.Results:Circ_0015278 exhibited downregulation in LUAD.It inhibited cell proliferation,migration,and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism.Moreover,circ_0015278 suppressed tumour growth in mice.Conclusions:Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD.Furthermore,it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.展开更多
Therapy-induced modulation of the tumor microenvironment(TME)to overcome the immunosuppressive TME is considered to be a chance for cancer treatment.Herein,we prepared near-infrared absorbing aza-BODIPY PhEt-azaBDP wi...Therapy-induced modulation of the tumor microenvironment(TME)to overcome the immunosuppressive TME is considered to be a chance for cancer treatment.Herein,we prepared near-infrared absorbing aza-BODIPY PhEt-azaBDP with 1-phenylethyl group at 1,7-sites,a type I photodynamic-photothermal therapy(PDT-PTT)agent.Self-assembly PhEt-azaBDP nanoparticles(NPs)can provide combined phototherapeutic effects under light irradiation and simultaneously induce inflammatory TME,by monitoring tumorassociated macrophages(TAMs)repolarization.Utilizing cluster of differentiation 86(CD86)and CD163 as the M1-type marker and M2-type marker respectively,PhEt-azaBDP NPs resulted in the increasement of the expression of CD86 and the decreasement of the expression of CD163 in TAMs under near-infrared(NIR)light irradiation,promoting TAMs to switch from M2-phenotype to M1-phenotype.Inflammatory cytokines,interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),could be the key cytokine involved in the phototherapy-induced TME reprogramming.PhEt-azaBDP NPs could be a potential theranostic scaffold for the simultaneous induction and detection of TME reprogramming triggered by phototherapy.展开更多
Liver fibrosis,a hallmark pathological endpoint of chronic aging-related liver diseases,remains a clinical challenge with limited therapeutic options.In healthy liver,myeloid cells constitute<5%of total hepatic imm...Liver fibrosis,a hallmark pathological endpoint of chronic aging-related liver diseases,remains a clinical challenge with limited therapeutic options.In healthy liver,myeloid cells constitute<5%of total hepatic immune cells,primarily comprising tissue-resident Kupffer cells.However,during aging or chronic injury,bone marrow-derived myeloid cell recruitment increases by two-to threefold in murine fibrotic models,reaching 15%-20% of intrahepatic immune populations.These infiltrating myeloid subsets exhibit functional plasticity,dynamically differentiating into pro-inflammatory mac-rophages or fibrosis-promoting Kupffer-like cells,contingent upon chemokine gradi-ents(e.g.,CCL2/CCR2 axis)and damage-associated molecular patterns(DAMPs).This review systematically examines the regulatory mechanisms of myeloid cells in liver fibrogenesis,with particular emphasis on their developmental origins,hepatic recruit-ment dynamics,functional heterogeneity,and pathogenic contributions to fibrosis.Furthermore,signaling pathways involving myeloid cells in liver fibrosis and therapeu-tic approaches modulating their differentiation and recruitment are discussed in this review.展开更多
The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes und...The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.展开更多
基金supported by the National KeyResearch and Development Program(No.2022YFC2009600 andNo.2022YFC2009601).
文摘Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods: The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30) was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, and pancreatic cancer). A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results: The average QoL score was 50.4 ± 10.8. The tumor type, age, sex, and TNM stage al had an impact on QoL ratings. Colorectal cancer patients had a better total QoL score(49.3 ± 10.3) and scores in the domains of functioning, with milder symptoms, except for diarrhea. Patients with biliary tract cancer(54.2 ± 12.3) and pancreatic cancer(54.2 ± 12.3) reported a poorer QoL, significant functional impairment, and more pronounced symptoms. Patients with esophageal cancer experienced the most severe financial difficulties(35.2 ± 27.5). Patients aged ≥65 years, women, and those with TNM stage Ⅲ/Ⅳ reported lower QoL. In addition, the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors, and based on ethnicity, educational level, occupation, treatment(s) received, and place of residence.Conclusions: There is a need to focus on elderly individuals, those with low educational levels, and patients with progressive malignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.
基金supported by Shandong Provincial Natural Science Foundation(no.ZR2020MH319).
文摘Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment options.Dysregulated microRNAs(miRNAs)are involved in various cellular processes in TNBC.Moreover,variations in the miRNA levels in TNBC may act as a dependable indicator for predicting the effectiveness and specificity of treatments.Currently,the application of miRNAs for breast cancer therapy is primarily in the preclinical stage,with a focus on identifying highly specific and sensitive miRNAs that could offer new possibilities for early diagnosis,clinical treat-ment,and prognostic monitoring of TNBC.
基金Supported by the Suzhou Medical Innovation Application Research Project(SZM2023027).
文摘AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.
基金supported by the National Natural Science Foundation of China (32070979)Shenzhen Science and Technology Program (JCYJ20220530161604009,JCYJ20240813150734043)+3 种基金Key Research and Development Program of Shaanxi (2024SF,YBXM,050)Fundamental Research Funds for the Central Universities (31020190QD004,3102019YX01001)Double First-Class Project of China Pharmaceutical University (CPUQNJC22_02)Global Pharmaceutical Development Alliance Plan of China Pharmaceutical University (1302090024-05)。
文摘DNA2,a multifunctional enzyme with structure-specific nuclease,5'-to-3'helicase,and DNA-dependent ATPase activities,plays a pivotal role in the cellular response to DNA damage.However,its involvement in cerebral ischemia/reperfusion(I/R)injury remains to be elucidated.This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout(cKO)mice(Nestin-Cre)subjected to middle cerebral artery occlusion(MCAO),an established model of cerebral I/R.Results demonstrated a gradual up-regulation of DNA2 expression,peaking at 72 h post-MCAO.Notably,DNA2 cKO mice exhibited more pronounced brain injury,neurological deficits,and neuronal apoptosis within the penumbra following MCAO.Additionally,DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation(OGD/R)cell culture model,and DNA2 knockdown(KD)exacerbated neuronal apoptosis and oxidative stress.Transcriptome analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of Homer1 in DNA2 cKO mice.Furthermore,in vitro experiments demonstrated that overexpression of Homer1a ameliorated DNA2 KD-induced neuronal apoptosis.Collectively,these findings demonstrate that DNA2 deficiency exacerbates cerebral I/R injury through the down-regulation of Homer1a,highlighting a novel regulatory axis in ischemic neuroprotection.
基金Supported by The Joint Special Project of Universities in Yunnan Province in 2022,No.2022-ES-530101-207The Hospital-level Scientific Research Project of The Fourth Affiliated Hospital of Dali University,No.2024YJ14.
文摘BACKGROUND Primary renal synovial sarcoma(PRSS)is extremely rare in clinical practice,and most cases are associated with SYT-SSX gene fusion.The PRSS with specific MDM2 gene amplification has not been reported so far.Therefore,there is no practical experience regarding the clinical,pathological features and diagnosis and treatment plans for patients of this type.This article reports a case of PRSS with specific MDM2 gene amplification.CASE SUMMARY The patient was preoperatively diagnosed with a malignant tumor of the left kidney(with a high probability of clear cell carcinoma).During the operation,a radical left nephrectomy was performed.The postoperative pathological examination report confirmed synovial sarcoma,and the gene test suggested PRSS with specific MDM2 gene amplification.Forty-eight days after the operation,the patient presented with"abdominal distension and diarrhea"and was found to have a huge metastatic tumor in the original left renal area.The patient died clinically 17 hours after admission due to"multiple organ failure".CONCLUSION PRSS with MDM2 gene amplification has a poorer prognosis,a higher degree of malignancy,and a faster progression,and clinicians need to be highly vigilant.
基金Supported by Science and Technology Program of Yunnan Provincial Department of Science and Technology-Basic Research Program,No.202301BA070001-025.
文摘BACKGROUND Diabetic retinopathy(DR)is one of the major eye diseases contributing to blindness worldwide.Endoplasmic reticulum(ER)stress in retinal cells is a key factor leading to retinal inflammation and vascular leakage in DR,but its mechanism is still unclear.AIM To investigate the potential mechanism of LEF1 and related RNAs in DR.METHODS ARPE-19 cells were exposed to high levels of glucose for 24 hours to simulate a diabetic environment.Intraperitoneally injected streptozotocin was used to induce the rat model of DR.The expression levels of genes and related proteins were measured by RT-qPCR and Western blotting;lnc-MGC and miR-495-3p were detected by fluorescent in situ hybridization;CCK-8 and TUNEL assays were used to detect cell viability and apoptosis;enzyme-linked immunosorbent assay was used to detect inflammatory factors;dual-luciferase gene assays were used to verify the targeting relationship;and the retina was observed by HE staining.RESULTS LEF1 and lnc-MGC have binding sites,and lnc-MGC can regulate the miR-495-3p/GRP78 molecular axis.In high glucose-treated cells,inflammation was aggravated,the intracellular reactive oxygen species concentration was increased,cell viability was reduced,apoptosis was increased,the ER response was intensified,and ferroptosis was increased.As an ER molecular chaperone,GRP78 regulates the ER and ferroptosis under the targeting of miR-495-3p,whereas inhibiting LEF1 can further downregulate the expression of lnc-MGC,increase the level of miR-495-3p,and sequentially regulate the level of GRP78 to alleviate the occurrence and development of DR.Animal experiments indicated that the knockdown of LEF1 can affect the lnc-MGC/miR-495-3p/GRP78 signaling axis to restrain the progression of DR.CONCLUSION LEF1 knockdown can regulate the miR-495-3p/GRP78 molecular axis through lnc-MGC,which affects ER stress and restrains the progression of DR and ferroptosis in retinal pigment epithelial cells.
文摘BACKGROUND The role of cerebral microvascular dysfunction in early cognitive impairment and dementia has become increasingly recognized.Furthermore,pathological changes in both Alzheimer’s disease and vascular dementia are almost always associated with cerebral hemodynamic deficits.AIM To investigate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)assessment of the blood-brain barrier(BBB)in combination with relevant plasma biomarkers for mild cognitive impairment(MCI).METHODS This study selected 50 patients with non-amnestic MCI(na-MCI group),52 patients with amnestic MCI(a-MCI group),and 55 healthy elderly controls(control group).The Chinese version of the Montreal cognitive assessment(MoCA),auditory verbal learning test(AVLT),Hamilton anxiety/depression scale(HAMA/HAMD),and activity of daily living(ADL)scales were used to analyze the characteristics of mental and behavioral symptoms of patients with MCI.The DCE-MRI technique was used to assess the contrast enhancement kinetics.The Patlak model was utilized to analyze the BBB permeability(volume transfer constants).Further,fasting blood was was used to quantify plasma homocysteine(Hcy),β-amyloid protein(Aβ)40,Aβ42,human phosphorylated tau-181 protein(p-tau181),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),and plasminogen activator inhibitor-1(PAI-1)levels,as well as serum neurofilament light chain(NFL)and glial fibrillary acidic protein(GFAP)concentrations.RESULTS The na-MCI and a-MCI groups demonstrated significantly lower MoCA and AVLT-Huashan version scores,and statistically higher HAMA,HAMD,and ADL scores compared to the control group.Moreover,the a-MCI group showed notably higher HAMA,HAMD,and ADL scores compared to the na-MCI group.Cranial MRI results revealed significant disparities in cerebral blood flow in the left and right frontal lobes,temporal lobes,hippocampi,cuneus,precuneus,parietal lobes,basal ganglia,and occipital lobes between the a-MCI and na-MCI groups.Compared to healthy controls,patients with MCI demonstrated a smaller amplitude of hippocampal contrast enhancement kinetics and a slower decay rate,indicating smaller vascular volume and increased BBB permeability.Further,Hcy,p-tau181,ICAM-1,VCAM-1,PAI-1,and NFL levels were substantially higher in the a-MCI group than in the na-MCI group,whereas the Aβ42 level was significantly lower.We did not observe any significant differences in Aβ40 and GFAP levels.CONCLUSION Patients with MCI may have experienced cerebrovascular system changes in the hippocampal region.Disorders associated with changes in cerebral blood supply may begin before pathophysiological changes are visible by imaging,which provides references for the assessment and treatment of patients with cognitive disorders.Further,DCE-MRI provides a noninvasive approach to diagnose subtle BBB leakage associated with cerebrovascular pathology.
文摘BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare.Most reported cases of metastatic invasive mole are diagnosed after surgery,and lack rich illustrations,which leads to insufficient understanding by clinicians,misdiagnosis,and unnecessary surgeries.CASE SUMMARY A 22-year-old female patient presented with bloody stool and elevated human chorionic gonadotropin.The transvaginal gynecological ultrasound ruled out pregnancy.Upper gastrointestinal endoscopy and colonoscopy were performed,but no bleeding focus was detected.The contrast-enhanced computed tomography was unremarkable.The capsule endoscopy suggested jejunal protuberant lesions with dark red blood clots.Therefore,oral single-balloon enteroscopy was performed,and two connected protuberant lesions were detected,with blood clot traces and local ulceration.The enteroscopic biopsy revealed trophoblastic cells with a probable diagnosis of trophoblastic tumor.The patient underwent surgical resection of the diseased jejunum.Intraoperative endoscopy was performed,and the findings were the same as those of the small intestine endoscopy.The postoperative pathology confirmed the preoperative diagnosis of invasive mole.CONCLUSION In non-pregnant women with elevated human chorionic gonadotropin and gastrointestinal bleeding,metastatic trophoblastic neoplasia should be considered.
文摘Objective:To evaluate the value of real-time two-dimensional shear wave elastography(SWE)in predicting liver parenchymal stiffness in non-alcoholic fatty liver disease(NAFLD).Methods:A total of 200 NAFLD patients(70 in the mild group,70 in the moderate group,and 60 in the severe group)and 60 healthy individuals(control group)who visited the hospital from December 2023 to December 2024 underwent real-time two-dimensional SWE examinations.Results:Except for high-density lipoprotein,comparisons of body mass index and biochemical indicators showed that the severe group>moderate group>mild group>control group,with P<0.05.Comparisons of liver stiffness values also showed that the severe group>moderate group>mild group>control group,with P<0.05.Pearson correlation analysis revealed a positive correlation between liver stiffness values and body mass index,triglycerides,total cholesterol,low-density lipoprotein,fasting blood glucose,and glycosylated hemoglobin.Analysis of the ROC curve indicated that the AUC,standard deviation,and P-value for liver stiffness values were 0.901,0.025,and 0.01,respectively,suggesting that liver stiffness values can predict the severity of NAFLD.Conclusion:The real-time two-dimensional shear wave elastography(SWE)technique for diagnosing NAFLD can differentiate between NAFLD patients and healthy individuals,as well as determine liver parenchymal stiffness,thereby assisting physicians in quantifying the degree of fatty liver.
文摘Background:To investigate adverse event(AE)signals associated with six proton pump inhibitors(PPIs),enhance drug labeling information,and provide guidance for their safe clinical use.Methods:Adverse reaction data for musculoskeletal and connective tissue disorders related to six PPI formulations—omeprazole,pantoprazole,lansoprazole,esomeprazole,rabeprazole,and dexlansoprazole—from Q12004 to Q42023 were collected from the FDA Adverse Event Reporting System(FAERS).Signal detection was performed using the Reporting Odds Ratio(ROR),Proportional Reporting Ratio(PRR),Bayesian Confidence Propagation Neural Network(BCPNN),and Empirical Bayesian Geometric Mean(EBGM).Data processing and statistical analysis were conducted using R Studio 4.40.Results:A total of 6,635,3,853,1,792,15,731,483,and 534 adverse events were identified for the six PPIs,respectively.The four algorithms(ROR,PRR,BCPNN,and EBGM)generated 17,19,8,27,5,and 2 positive signals.Notably,signals for renal osteodystrophy and osteoporosis were more frequent,with stronger signals for lumbar flexion syndrome and renal osteodystrophy.Conclusion:Patients with chronic kidney disease,a high risk of osteoporosis and fractures,or those using statins should select PPIs with a lower risk of adverse musculoskeletal and connective tissue reactions to minimize these adverse effects and ensure standardized clinical use of PPIs.
文摘BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with glucocorticoid(GCs)shock be-fore surgery,followed by surgical treatment,all of whom achieved good results.The effect of GCs on thymomas is related mainly to the action on GC receptors in thymic lymphocytes and epithelial cells.GC receptor expression has been asso-ciated with a better prognosis in patients with thymomas,including those with surgically removed thymomas.CASE SUMMARY We report a case of a patient with thymoma who had a significant response to preoperative low-dose GC therapy.A mediastinal tumor was detected in the patient via computerized tomography upon admission.The tumor was initially suspected to be a thymic tumor,but lymphoma could not be ruled out.The tumor shrank significantly after low-dose(5 mg/day)GC therapy.Thoracoscopic thy-moma resection was performed after puncture pathology was confirmed.The patient recovered well after the operation and is currently performing well with no recurrence of the tumor.CONCLUSION This case highlights that low-dose GCs are effective in the treatment of thymomas,and we believe that GCs should be applied more frequently and studied more thoroughly in the treatment of thymomas.
文摘BACKGROUND Gastrointestinal dual-contrast ultrasonography(DCUS)is characterized by its high resolution,sensitivity,and specificity.AIM To determine the accuracy of DCUS in predicting lymph node metastasis in middle-aged and elderly patients with gastric cancer(GC).METHODS A total of 100 middle-aged and elderly patients with GC admitted to the Fourth Affiliated Hospital of Soochow University(Dushu Lake Hospital,Suzhou,China)between April 2022 and April 2024 were selected.The baseline data and lymph node metastasis status were collected.DCUS combined with intravenous contrast technology was used to calculate the enhancement time(ET),time to peak(TTP),and slope of the ascending branch wash-in rate(WIR).These indicators were used in assessing lymph node metastasis in patients with GC.RESULTS Among 100 middle-aged and elderly patients with GC,35(35.00%)had lymph node metastases.GC patients with lymph node metastasis had a higher propor-tion of stage II TNM classification and higher WIR values than those without lymph node metastasis.The ET and TTP values were lower in patients with lymph node metastases,and all differences were statistically significant(P<0.05).The area under the curve values for ET,TTP,WIR,and combined diagnosis of GC lymph node metastasis using DCUS were all>0.7.Optimal assessment was achieved when the cutoff values for ET,TTP,and WIR were set at 16.32 seconds,10.67 seconds,and 7.02,res-pectively.CONCLUSION DCUS-mediated assessment of ET,TTP,and WIR can effectively predict and evaluate lymph node metastasis status in patients with GC,with higher sensitivity when used in combination.
基金Supported by the Science and Technology Development Fund of Nanjing Medical University,No.NMUB20230037the Youth Scientific Research Nurturing Fund of Jiangbei Campus of Zhongda Hospital Affiliated with Southeast University,No.JB2024Q01.
文摘BACKGROUND Accurate preoperative differentiation of benign and malignant thyroid nodules is critical for optimal patient management.However,conventional imaging modalities present inherent diagnostic limitations.AIM To develop a non-contrast computed tomography-based machine learning model integrating radiomics and clinical features for preoperative thyroid nodule classification.METHODS This multicenter retrospective study enrolled 272 patients with thyroid nodules(376 thyroid lobes)from center A(May 2021-April 2024),using histopathological findings as the reference standard.The dataset was stratified into a training cohort(264 lobes)and an internal validation cohort(112 lobes).Additional prospective temporal(97 lobes,May-August 2024,center A)and external multicenter(81 lobes,center B)test cohorts were incorporated to enhance generalizability.Thyroid lobes were segmented along the isthmus midline,with segmentation reliability confirmed by an intraclass correlation coefficient(≥0.80).Radiomics feature extraction was performed using Pearson correlation analysis followed by least absolute shrinkage and selection operator regression with 10-fold cross-validation.Seven machine learning algorithms were systematically evaluated,with model performance quantified through the area under the receiver operating characteristic curve(AUC),Brier score,decision curve analysis,and DeLong test for comparison with radiologists interpretations.Model interpretability was elucidated using SHapley Additive exPlanations(SHAP).RESULTS The extreme gradient boosting model demonstrated robust diagnostic performance across all datasets,achieving AUCs of 0.899[95%confidence interval(CI):0.845-0.932]in the training cohort,0.803(95%CI:0.715-0.890)in internal validation,0.855(95%CI:0.775-0.935)in temporal testing,and 0.802(95%CI:0.664-0.939)in external testing.These results were significantly superior to radiologists assessments(AUCs:0.596,0.529,0.558,and 0.538,respectively;P<0.001 by DeLong test).SHAP analysis identified radiomic score,age,tumor size stratification,calcification status,and cystic components as key predictive features.The model exhibited excellent calibration(Brier scores:0.125-0.144)and provided significant clinical net benefit at decision thresholds exceeding 20%,as evidenced by decision curve analysis.CONCLUSION The non-contrast computed tomography-based radiomics-clinical fusion model enables robust preoperative thyroid nodule classification,with SHAP-driven interpretability enhancing its clinical applicability for personalized decision-making.
基金Supported by the National Natural Science Foundation of China,No.82160192and Guangxi Science and Technology Program,No.2023AB23037.
文摘BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.
基金supported by the National Natural Science Foundation Committee of China(81971212,81601129)Shenyang Young and Middle-aged Technological Innovation Talent Support Program(RC210268)Liaoning Province Natural Science Foundation(2023-MS-153).
文摘Epilepsy is a devastating neurological condition that affects over 70 million people worldwide.Apart from idiopathic epilepsy,numerous diseases have been reported to cause secondary epilepsy.Polyphenols,ubiquitously existing in fruits and vegetables,has become a promising neuroprotective candidate against multiple neurological abnormalities due to its interplay with gut microbiome composed of the bacterial population in gastrointestinal system.This bioactive compound is also being tested for the management of epileptogenesis.However,there is still insufficient evidence from mechanistic studies to demonstrate the causal relationship between anti-epileptic effect of polyphenols and microbial alteration.In this review,we provide the brief overview of epilepsy,polyphenols and gut microbiota.We then analysis the association of polyphenols and gut microbiota particularly in the epilepsy and symptomatic seizures-induced by epilepsy related disorders.We also discuss the possibility for the combined application with probiotics to improve the bioavailability and bioaccessibility of polyphenols for expanding its anti-epileptic function.We finally summarize the therapeutic potential of anti-seizure polyphenols through affecting gut microbiome,and propose that the anti-epileptic effect of polyphenols may be tightly relevant to intestinal bacterial flora for overcoming epilepsy and its comorbidities simultaneously.Therefore,the dietary polyphenols targeting specific bacteria may achieve the outcome of‘one stone,two birds’.
文摘BACKGROUND Right ventricular hypertrophy(RVH)occurs because of volume or pressure overload within the right ventricular(RV)system.RVH is associated with complex pathological changes,including myocardial cell injury,apoptosis,myocardial fibrosis,neuroendocrine disturbances,and abnormal water and liquid metabolism.Ferroptosis,a novel type of iron-dependent cell death characterized by lipid peroxide accumulation,is an important mechanism of cardiomyocyte death.However,the role of ferroptosis in RVH has rarely been studied.We hypothesize that hydrogen(H_(2)),an experimental medical gas with superior distri-bution characteristics,inhibits ferroptosis.AIM To explore the protective effect of H_(2) on RVH and the mechanism by which H_(2) regulates ferroptosis.METHODS An in vivo RVH rat model was induced by monocrotaline(MCT)in 30 male Sprague-Dawley rats.An H9C2 cell model was treated with angiotensin II to simulate pressure overload in the RV system in vitro.H_(2) was administered to rats by inhalation(2%for 3 hours daily for 21 days)and added to the cell culture medium.The Nrf2 inhibitor ML385(1μM)was used to investigate anti-ferroptotic mechanisms.RESULTS In MCT-treated rats,H_(2) inhalation decreased RVH;the RV wall thickness decreased from 3.5±0.3 mm to 2.8±0.2 mm(P<0.05)and the RV ejection fraction increased from 45±3%to 52±4%(P<0.05).In H9C2 cells,H_(2) alleviated hypertrophy.H_(2) inhibited ferroptosis by modulating the iron content,oxidative stress,and ferroptosis-related proteins,thereby restoring the Nrf2/HO-1 signaling pathway.CONCLUSION H_(2) retards RVH by inhibiting ferroptosis via Nrf2/HO-1 restoration,suggesting a new treatment strategy.
基金Suzhou Youth Science and Technology Project(Grant Number KJXW2022006)Suzhou Science and Technology Plan Project(Grant Number SKY2022142)。
文摘Background:Circular RNAs play an important role in regulating lung adenocarcinoma(LUAD).Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD.However,the biological mechanism of circ_0015278 in LUAD has not been fully clarified,especially in ferroptosis.Materials and Methods:Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278,subsequently confirmed by luciferase reporter assays.The impact of Circ_0015278 on cell proliferation,migration,invasion,and ferroptosis was investigated through a loss-of-function experiment.A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth.Results:Circ_0015278 exhibited downregulation in LUAD.It inhibited cell proliferation,migration,and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism.Moreover,circ_0015278 suppressed tumour growth in mice.Conclusions:Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD.Furthermore,it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.
基金supported by the National Natural Science Foundation of China(Nos.22078201,U1908202)Liaoning&Shenyang Key Laboratory of Functional Dye and Pigment(Nos.2021JH13/10200018,21-104-0-23,LJKZ0453)China Medical University’s High-Quality Development Science and Technology Funding Program(Nos.2022JH2/20200063,2023JH2/20200162).
文摘Therapy-induced modulation of the tumor microenvironment(TME)to overcome the immunosuppressive TME is considered to be a chance for cancer treatment.Herein,we prepared near-infrared absorbing aza-BODIPY PhEt-azaBDP with 1-phenylethyl group at 1,7-sites,a type I photodynamic-photothermal therapy(PDT-PTT)agent.Self-assembly PhEt-azaBDP nanoparticles(NPs)can provide combined phototherapeutic effects under light irradiation and simultaneously induce inflammatory TME,by monitoring tumorassociated macrophages(TAMs)repolarization.Utilizing cluster of differentiation 86(CD86)and CD163 as the M1-type marker and M2-type marker respectively,PhEt-azaBDP NPs resulted in the increasement of the expression of CD86 and the decreasement of the expression of CD163 in TAMs under near-infrared(NIR)light irradiation,promoting TAMs to switch from M2-phenotype to M1-phenotype.Inflammatory cytokines,interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),could be the key cytokine involved in the phototherapy-induced TME reprogramming.PhEt-azaBDP NPs could be a potential theranostic scaffold for the simultaneous induction and detection of TME reprogramming triggered by phototherapy.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFA0804903National Natural Science Foundation of China,Grant/Award Number:882171545 and 91949125The Start-up Fund for Distinguished Research Fellows,the International Institute of Health Medicine,Zhejiang University,Grant/Award Number:Q22005。
文摘Liver fibrosis,a hallmark pathological endpoint of chronic aging-related liver diseases,remains a clinical challenge with limited therapeutic options.In healthy liver,myeloid cells constitute<5%of total hepatic immune cells,primarily comprising tissue-resident Kupffer cells.However,during aging or chronic injury,bone marrow-derived myeloid cell recruitment increases by two-to threefold in murine fibrotic models,reaching 15%-20% of intrahepatic immune populations.These infiltrating myeloid subsets exhibit functional plasticity,dynamically differentiating into pro-inflammatory mac-rophages or fibrosis-promoting Kupffer-like cells,contingent upon chemokine gradi-ents(e.g.,CCL2/CCR2 axis)and damage-associated molecular patterns(DAMPs).This review systematically examines the regulatory mechanisms of myeloid cells in liver fibrogenesis,with particular emphasis on their developmental origins,hepatic recruit-ment dynamics,functional heterogeneity,and pathogenic contributions to fibrosis.Furthermore,signaling pathways involving myeloid cells in liver fibrosis and therapeu-tic approaches modulating their differentiation and recruitment are discussed in this review.
基金supported by grants from STI2030-Major Projects,No.2021ZD0204000(to YS)Key Strategic Science and Technology Cooperation Project of the Ministry of Science and Technology of China,No.SQ2023YFE0201430(to YS)+1 种基金the National Natural Science Foundation of China,Nos.31820103005(to YS),32200620(to LW)the Natural Science Foundation of Zhejiang Province of China,No.LZ24C090003(to YS)。
文摘The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.
