Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.

Objective To investigate the clinical application of skin bridge preopening window drainage in enhanced recovery of mixed hemorrhoids surgically treated with external dissection and internal ligation.Methods A total of 620 patients with mixed hemorrhoids surgically treated with external dissection and internal ligation were retrospectively analyzed from March 1,2021-February 28,2022.Patients were divided into the observation group(n=304)and the control group(n=316)according to the single and even numbers randomly generated at the time of admission.In the observation group,on the basis of conventional operation and drug treatment in the control group,most of them chose to implement preopening window drainage of the skin bridge according to the intraoperative evaluation of the anal skin bridge according to the unified evaluation criteria.Symptom-sign scoring scale used to evaluate the anal edema and pain after the operation.To compare and analyze differences in anal edema,anal pain and the postoperative hospital stay between the observation group and the control.Results The average daily edema scores of the observation group and the control group were 0.56 and 1.2 points,respectively.The average daily edema score of the observation group was lower than that of the control group,with the statistically significant differences(P＜0.05).The average daily pain scores of the observation group and the control group were 0.6 and 1.201+0.289 points,respectively.The average daily pain score of the observation group was lower than that of the control group,with the statistically significant differences(P＜0.05).The average hospitalization days of the observation group and the control group were 8 days and 10 days,respectively.The average length of stay in the observation group was less than that in the control group,with the statistically significant differences(P＜0.05).Conclusion Skin bridge preopening window drainage can effectively relieve the degree of anal edema and pain in patients with mixed hemorrhoids surgically treated with external dissection and internal ligation,improve clinical efficacy,shorten the postoperative hospital stay.It has practical value and clinical significance for enhanced recovery.

Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.

Objective To investigate the relationship between left ventricular hypertrophy(LVH)diagnosed by Peguero-Lo-Presti index and recurrence of paroxysmal atrial fibrillation(AF)after radiofrequency ablation.Methods A total of 652 patients with paroxysmal atrial fibrillation who underwent radiofrequency ablation were selected.According to Peguero-Lo-Presti index,patients were divided into the LVH group(167 cases)and the normal left ventricle group(485 cases).Baseline data were collected,and regular follow-up was performed at 3,6 and 12 months after radiofrequency catheter ablation.The recurrence of AF was assessed.Kaplan-Meier survival curve was used to analyze the recurrence rate of AF in the two groups.Cox proportional hazard model was used to assess risk factors for recurrent atrial fibrillation.Results The median follow-up time was 20.5(15.0,26.0)months.A total of 155 patients(23.8%)developed recurrence of AF,including 95 patients in the LVH group and 60 patients in the LVN group.The recurrence rate without AF was significantly lower in the LVH group than that in the LVN group(64.1%vs.80.4%,Log-rank χ2=26.361,P＜0.01).After adjusting for age,sex,body mass index,hypertension,diabetes,coronary heart disease,cardiac dysfunction,left anteroposterior and posterior atrial diameter,left ventricular end-diastolic diameter,and left ventricular ejection fraction,LVH diagnosed by Peguero-Lo-Presti index was still a risk factor for recurrent AF[HR(95%CI):2.359(1.663-3.345),P＜0.01].Conclusion In patients with paroxysmal AF,LVH diagnosed by Peguero-Lo-Presti index is a risk factor of AF recurrence after radiofrequency catheter ablation.

BACKGROUND:It has been shown that neural stem cells can differentiate into neurons,astrocytes,and oligodendrocytes.Mesenchymal stem cells-derived extracellular vesicles have also been shown to cross the blood-brain barrier to reach sites of central nervous injury and promote neural repair.However,it is not clear whether neuron-derived extracellular vesicles promote the differentiation of neural stem cells in a direction that is beneficial for neurogenesis. OBJECTIVE:To investigate whether neuron-derived extracellular vesicles facilitate neural stem cell differentiation towards neurogenesis. METHODS:Neurons and neural stem cells were extracted from neonatal SD rat cerebral cortex by trypsin digestion.Cell supernatants of neurons were collected.Neuron-derived extracellular vesicles were extracted.Neural stem cells cultured for 10 days were co-cultured with neuron-derived extracellular vesicles or PBS for 7 days.Immunoblotting,immunofluorescence,and RT-qPCR were used to detect proteins specifically expressed by neurons,neural stem cells,oligodendrocytes,and astrocytes. RESULTS AND CONCLUSION:The neural stem cells co-cultured with neuron-derived extracellular vesicles showed high expression of neuron-specific proteins and oligodendrocyte-specific proteins including β3-tubulin,neurofilament 200 and myelin basic protein,and low expression of astrocyte-specific protein glial fibrillary acidic protein.These results suggest that neuron-derived extracellular vesicles can promote the differentiation of neural stem cells into neurons and oligodendrocytes and prevent the differentiation of neural stem cells into astrocytes.

BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.