Objective To investigate the short-term efficacy of the retrograde semi-retrieval technique(RESET)in the treatment of patients with acute intracranial large vessel occlusion.Methods This retrospective study involved 286 patients with acute intracranial large vessel occlusion who underwent mechanical thrombectomy using RESET at Tianjin Huanhu Hospital from November 2017 to March 2019.The patients were divided into two groups based on the presence or absence of intracranial atherosclerotic stenosis(ICAS):ICAS group(n=186,65％)and non-ICAS group(n=100,35％).Baseline characteristics,procedural outcomes,and 90-day modified Rankin Scale(mRS)scores were compared between the two groups.Results The two groups did not significantly differ in baseline characteristics,including age,gender,past medical history,on-admission National Institutes of Health Stroke Scale(NIHSS)score,and Alberta Stroke Program Early CT(ASPECT)score(all P＞0.05).Successful vascular recanalization was achieved in 272 patients(95.1％),with 209 patients(73.1％)achieving complete recanalization with a single thrombectomy attempt.Rescue therapy was required in 33 patients(11.5％).Two patients in the ICAS group died due to postoperative symptomatic intracranial hemorrhage,and one patient in the non-ICAS group died due to postoperative multiple organ failure.Compared with the non-ICAS group,the ICAS group had a significantly longer puncture-to-recanalization time[141.36(124.11,156.53)min vs.65.17(53.92,83.25)min,P＜0.001]but a significantly smaller number of thrombectomy attempts[1.00(1.00,1.00)vs.1.00(1.00,2.00),P=0.002].However,there were no significant differences between the two groups in terms of final recanalization rate,complete recanalization rate with a single thrombectomy attempt,distal embolism or embolization of new territory,symptomatic intracranial hemorrhage,perioperative death,or 90-day mRS score(all P＞0.05).Conclusion RESET demonstrates satisfactory short-term efficacy in the treatment of acute intracranial large vessel occlusion.The number of thrombectomy attempts required for complete recanalization is significantly lower in the ICAS group than in the non-ICAS group,suggesting that RESET is particularly suitable for patients with ICAS.

Objective To develop a neural network-based deep learning model for predicting postoperative recurrence in thyroid tumor patients and validate the model with external datasets for providing clinicians with a reliable decision support tool.Methods An artificial neural network structure was adopted in the study,with thyroid tumor data from the SEER database serving as the training set.External validation was conducted with open-source data from the University of California,Irvine(UCIrvine),and the data from 100 patients at a general tertiary hospital in Hunan province.The model's accuracy and reliability in predicting recurrence were evaluated through multiple performance metrics.Results Experimental results showed that the model outperformed Logistic model in recurrence prediction,with accuracy,recall rate,precision and F1 score reaching 0.915 3,0.981 8,0.921 1 and 0.947 4 in internal validation.Moreover,the model achieved accuracies,recall rates,precisions,F1 scores and ROC_AUC values of 0.832 9,0.945 5,0.841 4,0.890 4 and 0.78 on the UCIrvine validation set,while 0.870 0,0.880 0,0.862 7,0.871 3 and 0.80 on the local validation set.Conclusion This neural network-based predictive model exhibits excellent performance in thyroid tumor recurrence prediction,providing clinicians with a valuable decision support tool that can help optimize postoperative treatment plans and improve patient prognosis management.

OBJECTIVE: To elucidate the role and mechanism of microRNA-145-5p (miR-145-5p) in hypoxia-induced pyroptosis of human alveolar epithelial cells. METHODS: In vitro, human alveolar epithelial cell line BEAS-2B was cultured. Cells in the logarithmic growth phase were cultured to 80% confluence and then used for the experiment. (1) BEAS-2B cells were cultured under 1% O₂ hypoxic condition, with a normoxic control group. Western blotting was employed to detect the expressions of pyroptosis marker proteins [NOD-like receptor protein 3 (NLRP3), Gasdermin D N-terminal domain (GSDMD-N), and caspase-1] in cells cultured for 24 hours. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of miR-145-5p in cells cultured for 6 hours and 12 hours. (2) Cells were transfected with 30 nmol/L miR-145-5p mimic to overexpress miR-145-5p expression under normoxic condition or 30 nmol/L miR-145-5p inhibitor to suppress miR-145-5p expression under hypoxic condition. Control group and negative control group were respectively set up. After 24 hours of cell culture, Western blotting was used to detect the expressions of pyroptosis marker proteins and nuclear factor-E2-related factor 2 (Nrf2) in cells. Flow cytometry was applied to detect the level of reactive oxygen species (ROS) in cells. The target genes of miR-145-5p were predicted by miR target gene prediction software miRWalk and verified by Western blotting. (3) Under hypoxic condition, cells were transfected with 6.94 ng/μL silent information regulator 5 (Sirt5) overexpression plasmid or pretreated with 12.5 mmol/L N-acetyl-L-cysteine (NAC) as an ROS inhibitor. The empty plasmid group and control group were set up. After 24 hours of cell culture, Western blotting was used to detect the expressions of Sirt5, Nrf2, and pyroptosis marker proteins in cells. Flow cytometry was used to detect the level of ROS in cells. RESULTS: (1) Compared with the normoxic control group, the expression levels of pyroptosis marker proteins in the 24-hour hypoxia group was significantly increased, indicating that hypoxia could induce pyroptosis in BEAS-2B cells. The expression level of miR-145-5p in cells gradually increased with the extension of hypoxia induction time, indicating that hypoxia could cause the increase of miR-145-5p expression level. (2) The expression levels of pyroptosis marker proteins in cells of miR-145-5p mimic group significantly increased under normoxic condition as compared with the control and negative control groups [NLRP3 protein (NLRP3/β-actin): 1.58±0.07 vs. 1.00±0.01, 0.98±0.07, GSDMD-N protein (GSDMD-N/β-actin): 1.71±0.03 vs. 1.01±0.01, 0.85±0.03, caspase-1 protein (caspase-1/β-actin): 2.33±0.04 vs. 1.01±0.01, 1.05±0.04, all P < 0.05], Nrf2 protein expression level was significantly decreased (Nrf2/β-actin: 0.79±0.03 vs. 1.00±0.01, 1.03±0.04, both P < 0.05), ROS level was significantly up-regulated (fluorescence intensity: 1.74±0.03 vs. 1.00±0.01, 0.92±0.03, both P < 0.05). Under hypoxia condition, compared with control group and negative control group, the expression levels of pyroptosis marker proteins in miR-145-5p inhibitor group were significantly decreased [NLRP3 protein (NLRP3/β-actin): 0.21±0.04 vs. 1.70±0.02, 1.63±0.04; GSDMD-N protein (GSDMD-N/β-actin): 1.32±0.02 vs. 2.51±0.02, 2.72±0.03; caspase-1 protein (caspase-1/β-actin): 0.56±0.01 vs. 2.77±0.02, 3.12±0.03; all P < 0.05], Nrf2 protein expression level was significantly increased (Nrf2/β-actin: 1.57±0.04 vs. 1.22±0.01, 1.28±0.04, both P < 0.05), ROS level was significantly down-regulated (fluorescence intensity: 0.64±0.05 vs. 1.87±0.04, 1.70±0.07, both P < 0.05). The results indicated that miR-145-5p could promote cell pyrodeath. The predictive result of miRWalk showed that the 3' untranslated region (3'UTR) of Sirt5 had complementary base binding sites with miR-145-5p. The expression level of Sirt5 protein in cells of miR-145-5p mimic group was significantly lower than that of control group and negative control group under normoxic condition (Sirt5/β-actin: 0.59±0.03 vs. 1.00±0.01, 1.01±0.03, both P < 0.05), which verified that Sirt5 was the target gene of miR-145-5p. (3) The occurrence of pyrodeath could be partially reversed by transfection with Sirt5 overexpression plasmid or adding ROS inhibitor NAC into cells, and Sirt5 overexpression could also up-regulate Nrf2 expression and eliminate intracellular ROS. CONCLUSION In human alveolar epithelial cells, miR-145-5p can down-regulate Nrf2 by targeting Sirt5, thereby increasing ROS expression and inducing pyrodeath.
Humans ; MicroRNAs ; Pyroptosis ; Cell Hypoxia ; Alveolar Epithelial Cells/cytology* ; Cell Line ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1/metabolism* ; Epithelial Cells/metabolism* ; Gasdermins ; Phosphate-Binding Proteins

Objective To compare the efficacy and safety of perioperative chemotherapy regimens based on docetaxel administered in different cycles for locally advanced gastric cancer(LAGC)and gastroesophageal junction cancer(GEJC)through a network Meta-analysis.Methods PubMed,Embase,Cochrane Library,and Web of Science databases were electronically searched to collect randomized controlled trials(RCTs)evaluating docetaxel-based perioperative regimens for the treatment of LAGC and GEJC from inception to February 28,2025.Two researchers independently screened the literature,extracted relevant data,and assessed the risk of bias in the included studies.Subsequently,a network Meta-analysis was performed using R 4.5.0 software.Results A total of 10 RCTs involving 2,064 patients were included.The results of the network Meta-analysis showed that,compared with three cycles of epirubicin,cyclophosphamide,and fluorouracil(ECF regimen)and four cycles of platinum and fluorouracil(PF regimen),both three-cycle and four-cycle docetaxel,platinum,and fluorouracil(TPF regimen)significantly increased the complete tumor resection rate(R0 resection rate).Compared with surgery alone,the three-cycle TPF regimen significantly improved the R0 resection rate.Additionally,the four-cycle TPF regimen significantly improved 3-year and 5-year progression-free survival(PFS)compared with the two-cycle PF regimen,and significantly improved overall survival(OS)at 3 and 5 years compared with the three-cycle ECF regimen.Compared with surgery alone,the three-cycle TPF regimen also significantly increased the pathological complete response rate(pCR rate).Furthermore,compared with the two-cycle TPF and three-cycle ECF regimens,the four-cycle TPF and PF regimens were associated with a lower risk of surgical complications.Conversely,the two-cycle TPF and three-cycle ECF regimens significantly increased the risk of surgical complications compared with surgery alone.No statistically significant differences were observed in the incidence of grade 3 to 4 adverse events among the treatment regimens(P＞0.05).Based on the surface under the cumulative ranking curve(SUCRA)plot and pairwise comparisons,the three-cycle PF regimen appeared to be the most effective in achieving the highest R0 resection rate,the three-cycle TPF regimen appeared to be the most effective in achieving the highest pCR rate,while the four-cycle TPF regimen was associated with the best outcomes in terms of 3-year and 5-year PFS and OS.Conclusion The four-cycle TPF regimen may be associated with the optimal PFS and OS among perioperative chemotherapy regimens.No statistically significant differences were observed between the four-cycle TPF and the three-cycle PF in terms of R0 resection rate,between the four-cycle TPF and the three-cycle TPF in terms of pCR rate,or between the four-cycle TPF and the other seven regimens included in the study in terms of safety assessment.The four-cycle TPF regimen may represent the optimal perioperative chemotherapy regimen for patients with LAGC and GEJC.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Objective To develop a neural network-based deep learning model for predicting postoperative recurrence in thyroid tumor patients and validate the model with external datasets for providing clinicians with a reliable decision support tool.Methods An artificial neural network structure was adopted in the study,with thyroid tumor data from the SEER database serving as the training set.External validation was conducted with open-source data from the University of California,Irvine(UCIrvine),and the data from 100 patients at a general tertiary hospital in Hunan province.The model's accuracy and reliability in predicting recurrence were evaluated through multiple performance metrics.Results Experimental results showed that the model outperformed Logistic model in recurrence prediction,with accuracy,recall rate,precision and F1 score reaching 0.915 3,0.981 8,0.921 1 and 0.947 4 in internal validation.Moreover,the model achieved accuracies,recall rates,precisions,F1 scores and ROC_AUC values of 0.832 9,0.945 5,0.841 4,0.890 4 and 0.78 on the UCIrvine validation set,while 0.870 0,0.880 0,0.862 7,0.871 3 and 0.80 on the local validation set.Conclusion This neural network-based predictive model exhibits excellent performance in thyroid tumor recurrence prediction,providing clinicians with a valuable decision support tool that can help optimize postoperative treatment plans and improve patient prognosis management.

Objective To compare the efficacy and safety of perioperative chemotherapy regimens based on docetaxel administered in different cycles for locally advanced gastric cancer(LAGC)and gastroesophageal junction cancer(GEJC)through a network Meta-analysis.Methods PubMed,Embase,Cochrane Library,and Web of Science databases were electronically searched to collect randomized controlled trials(RCTs)evaluating docetaxel-based perioperative regimens for the treatment of LAGC and GEJC from inception to February 28,2025.Two researchers independently screened the literature,extracted relevant data,and assessed the risk of bias in the included studies.Subsequently,a network Meta-analysis was performed using R 4.5.0 software.Results A total of 10 RCTs involving 2,064 patients were included.The results of the network Meta-analysis showed that,compared with three cycles of epirubicin,cyclophosphamide,and fluorouracil(ECF regimen)and four cycles of platinum and fluorouracil(PF regimen),both three-cycle and four-cycle docetaxel,platinum,and fluorouracil(TPF regimen)significantly increased the complete tumor resection rate(R0 resection rate).Compared with surgery alone,the three-cycle TPF regimen significantly improved the R0 resection rate.Additionally,the four-cycle TPF regimen significantly improved 3-year and 5-year progression-free survival(PFS)compared with the two-cycle PF regimen,and significantly improved overall survival(OS)at 3 and 5 years compared with the three-cycle ECF regimen.Compared with surgery alone,the three-cycle TPF regimen also significantly increased the pathological complete response rate(pCR rate).Furthermore,compared with the two-cycle TPF and three-cycle ECF regimens,the four-cycle TPF and PF regimens were associated with a lower risk of surgical complications.Conversely,the two-cycle TPF and three-cycle ECF regimens significantly increased the risk of surgical complications compared with surgery alone.No statistically significant differences were observed in the incidence of grade 3 to 4 adverse events among the treatment regimens(P＞0.05).Based on the surface under the cumulative ranking curve(SUCRA)plot and pairwise comparisons,the three-cycle PF regimen appeared to be the most effective in achieving the highest R0 resection rate,the three-cycle TPF regimen appeared to be the most effective in achieving the highest pCR rate,while the four-cycle TPF regimen was associated with the best outcomes in terms of 3-year and 5-year PFS and OS.Conclusion The four-cycle TPF regimen may be associated with the optimal PFS and OS among perioperative chemotherapy regimens.No statistically significant differences were observed between the four-cycle TPF and the three-cycle PF in terms of R0 resection rate,between the four-cycle TPF and the three-cycle TPF in terms of pCR rate,or between the four-cycle TPF and the other seven regimens included in the study in terms of safety assessment.The four-cycle TPF regimen may represent the optimal perioperative chemotherapy regimen for patients with LAGC and GEJC.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Objective To investigate the short-term efficacy of the retrograde semi-retrieval technique(RESET)in the treatment of patients with acute intracranial large vessel occlusion.Methods This retrospective study involved 286 patients with acute intracranial large vessel occlusion who underwent mechanical thrombectomy using RESET at Tianjin Huanhu Hospital from November 2017 to March 2019.The patients were divided into two groups based on the presence or absence of intracranial atherosclerotic stenosis(ICAS):ICAS group(n=186,65％)and non-ICAS group(n=100,35％).Baseline characteristics,procedural outcomes,and 90-day modified Rankin Scale(mRS)scores were compared between the two groups.Results The two groups did not significantly differ in baseline characteristics,including age,gender,past medical history,on-admission National Institutes of Health Stroke Scale(NIHSS)score,and Alberta Stroke Program Early CT(ASPECT)score(all P＞0.05).Successful vascular recanalization was achieved in 272 patients(95.1％),with 209 patients(73.1％)achieving complete recanalization with a single thrombectomy attempt.Rescue therapy was required in 33 patients(11.5％).Two patients in the ICAS group died due to postoperative symptomatic intracranial hemorrhage,and one patient in the non-ICAS group died due to postoperative multiple organ failure.Compared with the non-ICAS group,the ICAS group had a significantly longer puncture-to-recanalization time[141.36(124.11,156.53)min vs.65.17(53.92,83.25)min,P＜0.001]but a significantly smaller number of thrombectomy attempts[1.00(1.00,1.00)vs.1.00(1.00,2.00),P=0.002].However,there were no significant differences between the two groups in terms of final recanalization rate,complete recanalization rate with a single thrombectomy attempt,distal embolism or embolization of new territory,symptomatic intracranial hemorrhage,perioperative death,or 90-day mRS score(all P＞0.05).Conclusion RESET demonstrates satisfactory short-term efficacy in the treatment of acute intracranial large vessel occlusion.The number of thrombectomy attempts required for complete recanalization is significantly lower in the ICAS group than in the non-ICAS group,suggesting that RESET is particularly suitable for patients with ICAS.

Humans ; Pulmonary Alveolar Proteinosis/radiotherapy* ; Small Cell Lung Carcinoma/radiotherapy* ; Lung ; Bronchoalveolar Lavage ; Lung Neoplasms/radiotherapy*