Objective To discuss the curative effect of hepatic arterial infusion chemotherapy(HAIC)combined with programmed death receptor-1(PD-1)inhibitors and anti-angiogenesis therapy for BCLC stage C hepatocellular carcinoma(HCC).Methods The patients with HCC of BCLC stage C,who received HAIC combined with PD-1 inhibitors and anti-angiogenesis therapy at the First Affiliated Hospital of Soochow University of China from January 2021 to December 2023,were collected for this study.The time from the start of treatment to complete remission(CR)of disease,the dynamic changes in alpha-fetoprotein(AFP)levels and the recurrence during follow-up period were analyzed.The relevant literature of the above triple regimen for HCC was searched from PubMed database and its curative effect was analyzed.Results Of the 214 HCC patients treated with triple therapy regimen,9(4.2％)achieved CR.The time from the start of treatment to CR was 2-10 months.The patients were followed up for 5-20 months.The time of AFP level returning to normal value was from 79 to 259 days.One patient developed recurrence 10 months after CR,and the other 8 patients maintained the CR status.A total of 12 articles were retrieved,the reported CR rates ranged from 0 to 16.5％.Conclusion A CR can be achieved in a few patients with advanced HCC treated with HAIC combined with PD-1 inhibitors and anti-angiogenesis therapy.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

Objective To investigate the correlation between the level of platelet autophagy related factors and the neurological impairment and prognosis of the patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods From July 2020 to March 2023,90 aSAH patients admitted to the intensive care unit of neurosurgery department of our hospital were analyzed retrospectively.Based on mRS score 3 months after discharge,patients with aSAH(n=46,mRS 0-2)were divided into the good prognosis group,while those with mRS 3-5(n=44)as the poor prognosis group.Platelets of all the participants were collected,and the levels of autophagy-associated protein 7(ATG7),benzalkonium chloride 1(BECN1),microtubule-associated protein 1 light chain 3(LC3)and sequestosome 1(p62)were determined by enzyme-linked immunosorbent assay(ELISA).Results Compared with the good prognosis group,the mechanical ventilation time,ICU stay,cases of early brain injury,vasospasm and delayed cerebral ischemia in the poor prognosis group increased significantly(P<0.05).Compared with the good prognosis group,the ΔPLT in the poor prognosis group decreased significantly(P<0.05),and ΔLC3-Ⅱ and ΔATG7 increased significantly(P<0.05).Spearman correlation analysis showed that ΔPLT was positively correlated with ΔATG7,ΔLC3-Ⅱ and ΔBECN1(r=0.239,0.389 and 0.487,all P<0.05).Platelet ΔLC3-Ⅱ in patients with vasospasm and delayed cerebral ischemia was higher than that in patients without vasospasm and delayed cerebral ischemia(P<0.05).ICU stay(OR=1.187,95%CI=1.045～1.349,P=0.008),ΔPLT(OR=0.972,95%CI=0.947～0.998,P=0.034)and ΔLC3-Ⅱ(OR=2.840,95%CI=1.049～7.694,P=0.040)were independent influencing factors for the poor prognosis of aSAH patients.The combination of ICU stay,ΔPLT and ΔLC3-Ⅱ had the greatest ability to predict the poor prognosis of aSAH patients,with AUC of 0.921,sensitivity of 86.4%and specificity of 84.8%.Conclusion The decrease of platelet count and LC3-Ⅱ improvement in early treatment of aSAH patients can be regarded as the independent influencing factors of adverse outcomes.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.