Objective To evaluate the effect of LifePort combined with polymyxin B in preventing donor-derived infections caused by preservation solution contamination. Methods Clinical data of 110 kidney transplant recipients were retrospectively analyzed. According to the decontamination status of preservation solution, the recipients were divided into the decontamination group (n=62) and the non-decontamination group (n=48). The general data of the two groups were compared, and the preventive effect of polymyxin B on possible donor-derived infections (p-DDI) was analyzed, especially infections associated with multidrug-resistant Gram-negative bacteria (MDR GNB). Results There were no statistically significant differences in baseline data (gender, age, preservation solution contamination status, etc.) between the decontamination group and the non-decontamination group (all P > 0.05). The overall contamination rate of preservation solution was 80.0%, and 68 contaminated samples were with single microorganism and 20 with multiple microorganisms. Coagulase-negative staphylococci, Enterococcus and Klebsiella pneumoniae were the most common microorganisms in the positive samples. Fifteen cases of preservation solution were contaminated by MDR GNB, including 10 cases in the non-decontamination group and 5 cases in the decontamination group, with no statistically significant difference between the two groups (P = 0.053). Postoperative infection-related events occurred in 69 recipients, including 39 cases in the non-decontamination group and 30 cases in the decontamination group, with the incidence rate in the non-decontamination group significantly higher than that in the decontamination group (P < 0.001). Only 10 cases of infections were identified as p-DDI, all of which were positive for preservation solution culture, including 8 cases in the non-decontamination group and 2 cases in the decontamination group (P < 0.05). There were 5 cases of p-DDI related to MDR GNB in the non-decontamination group, while no such cases occurred in the decontamination group (P < 0.05). No adverse reactions related to polymyxin B were observed, and no recipient death or renal allograft dysfunction occurred in either group. Conclusions Adding polymyxin B to the preservation fluid during hypothermic machine perfusion with LifePort before renal transplantation may reduce p-DDI and its potential adverse consequences.

OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

ObjectiveTo investigate the efficacy and safety of lenvatinib combined with sintilimab versus atezolizumab combined with bevacizumab in patients with unresectable hepatocellular carcinoma （uHCC）， aims to provide real-world evidence for clinical personalized treatment. MethodsA retrospective analysis was performed for 78 patients with uHCC who were admitted to Beijing Ditan Hospital， Capital Medical University， from January 1， 2023， to May 31， 2025， and according to the treatment modality， they were divided into lenvatinib+sintilimab group （L+S group with 49 patients） and atezolizumab+bevacizumab group （A+T group with 29 patients）. The primary endpoints were progression-free survival （PFS） and overall survival （OS）， and the secondary endpoints included objective response rate （ORR）， disease control rate （DCR）， and the incidence rate of adverse events. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for survival analysis， and the log-rank test was used for comparison between groups. ResultsThe 78 patients had a median PFS of 9 months and a median OS of 15 months. The median PFS was 11 months in the L+S group and 7 months in the A+T group， with no significant difference between the two groups （χ²=0.247， P=0.619）； the median OS was 19 months in the L+S group and 12 months in the A+T group， with a significant difference between the two groups （χ²=6.565， P=0.010）. There were no significant differences between the two groups in complete remission， partial remission， stable disease， disease progression， DCR， and ORR （all P>0.05）. The L+S group had a significantly higher incidence rate of adverse events than the A+T group （95.9% vs 75.9%， P=0.007）， and there was a significant difference in the incidence rate of grade ≥3 adverse events between the L+S group and the A+T group （65.3% vs 34.5%， P=0.008）. ConclusionCompared with atezolizumab combined with bevacizumab， lenvatinib combined with sintilimab can improve the OS of patients with uHCC， while atezolizumab combined with bevacizumab has a better safety profile.

ObjectiveTo explore the mechanisms through which Si Junzitang （SJZD） ameliorates Alzheimer's disease （AD） induced by scopolamine （SCOP） in mice and the PC12 cell model induced by H₂O₂ based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsIn the animal experiments， an AD model was established in mice by intraperitoneal injection of SCOP （3 mg·kg^-1）. Morris water maze and open field tests （OFT） were conducted to assess learning and memory abilities. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe pathological changes in neurons. Immunofluorescence was used to detect amyloid β-protein_1-42 （Aβ_1-42） expression， and immunohistochemistry was employed to detect phosphorylated （p）-Tau expression. Transmission electron microscopy （TEM） was employed to observe ultrastructural changes in hippocampal neurons and synapses. Biochemical methods were used to measure the levels of acetylcholine （ACh）， acetylcholinesterase （AChE）， superoxide dismutase （SOD）， malondialdehyde （MDA）， catalase （CAT）， and lactate dehydrogenase （LDH）. Real-time PCR and Western blot were employed to measure the mRNA and protein levels of molecules in the Keap1/Nrf2/HO-1 pathway in the hippocampus. In the cell experiments， a PC12 cell model of oxidative damage model was established with H₂O₂. Cell count kit-8 （CCK-8） assays and flow cytometry were adopted to measure cell viability and apoptosis rates， and Western blot was employed to quantify the expression levels of proteins in the Keap1/Nrf2/HO-1 pathway. ResultsThe animal experiments showed that compared with the model group， the SJZD and donepezil groups showed shortened escape latency （P<0.01）， increased time in the target quadrant and platform crossings， and increased movement distance and duration in the central area of the open field （P<0.05， P<0.01）. HE and Nissl staining showed more organized neurons and increased Nissl bodies in the drug intervention groups （P<0.05， P<0.01）， and the Aβ_1-42 and p-Tau expression levels were downregulated （P<0.05， P<0.01）. TEM revealed reduced ultrastructural damage in hippocampal neurons and synapses in the drug intervention groups. In addition， the drug intervention groups showed declined levels of MDA， LDH， and AChE （P<0.05， P<0.01）， elevated levels of SOD， CAT， and ACh （P<0.05， P<0.01）， reduced Keap1 expression and increased Nrf2， HO-1， and NQO1 expression in the hippocampus （P<0.05， P<0.01）. The cell experiments showed that compared with the model group， the SJZD-containing serum increased the cell viability （P<0.05， P<0.01）， and decreased total apoptosis rates （P<0.05， P<0.01）. The drug intervention groups showed upregulated protein levels of Nrf2 and HO-1 and downregulated protein level of Keap1 （P<0.05， P<0.01）. ConclusionSJZD demonstrates protective effects against SCOP-induced AD in mice and H₂O₂-induced damage in PC12 cells through antioxidant mechanisms mediated by the Keap1/Nrf2/HO-1 pathway.

ObjectiveTo investigate the efficacy and safety of atezolizumab combined with bevacizumab versus sintilimab combined with bevacizumab biosimilar in the treatment of patients with unresectable hepatocellular carcinoma （HCC） in a real-world setting， and to provide a reference for clinical practice. MethodsA retrospective analysis was performed for 130 patients with unresectable HCC who were treated in Beijing Ditan Hospital， Capital Medical University， from January 2020 to January 2026， and all patients received the first-line systemic therapy with immune checkpoint inhibitors combined with bevacizumab or its biosimilar. According to the treatment regimen， the patients were divided into atezolizumab+bevacizumab group （T+A group with 51 patients） and sintilimab+bevacizumab biosimilar group （Shuangda group with 79 patients）. The primary endpoint was progression-free survival （PFS）， and secondary endpoints included objective response rate （ORR）， disease control rate （DCR）， and safety profile. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for survival analysis， and the Log-rank test was used for comparison between groups. ResultsThe T+A group had a median PFS of 297.00 days （95% confidence interval ［CI］： 195.44 — 398.56）， and the Shuangda group had a median PFS of 236.00 days （95%CI： 165.10 — 306.90）， with no significant difference between the two groups （P=0.668）. There were no significant differences between the T+A group and the Shuangda group in ORR （56.9% vs 45.6%， χ²=1.581， P=0.209）， DCR （76.5% vs 77.2%， χ²=0.010， P=0.922）， and the incidence of adverse events （96.08% vs 94.94%， P>0.05）. ConclusionFor unresectable HCC patients without prior systemic treatment， atezolizumab combined with bevacizumab can achieve a comparable PFS to sintilimab combined with bevacizumab biosimilar.

Objective To analyze the risk factors and re-intervention strategies for mid- and long-term residual after arterial switch operation (ASO). Methods The clinical data of children with complex congenital heart disease who underwent ASO surgery in Shanghai Children’s Medical Center from January 2006 to June 2022 were retrospectively collected, and the risk factors for mid- and long-term residual after ASO were analyzed. Results A total of 952 children undergoing ASO were enrolled in this study, including 654 males and 298 females with an average age of (102.9±90.1) d and weight of (4.6±1.6) kg. There were 421 patients with D-transposition of the great arteries with intact ventricular septum (D-TGA/IVS), 357 patients with D-transposition of the great arteries with ventricular septal defect (D-TGA/VSD), and 174 patients with right ventricle double outlet combined with subpulmonary ventricular septal defect (Taussig-Bing malformation). Eighty-nine patients died early after the surgery, the mortality rate was 9.3%. The 746 surviving children were regularly followed up after the surgery (follow-up rate 86.4%), with a median follow-up time of 79.4 (12.0-188.0) months. During the follow-up, 53 children underwent surgical re-intervention due to residual, including 33 males and 20 females, with a median age of 62.5 (17.0-214.0) months. The median surgical weight was 19.0 (8.2-86.0) kg, and the mean time of re-intervention was 28.0-170.0 (77.5±45.4) months after the ASO. Residual problems included common trunk and branch stenosis of the pulmonary artery in 23 patients, right ventricular outflow tract (RVOT) obstruction in 11 patients, left ventricular outflow tract obstruction in 6 patients, aortic arch restenosis in 5 patients, aortic insufficiency in 5 patients, residual shunt of ventricular septal defect in 2 patients, and tricuspid valve insufficiency in 1 patient. The early postoperative mortality rate was 3.8% (2/53), with the causes of death being acute myocardial infarction due to coronary artery injury and acute left heart failure, respectively. The mean follow-up time of the surviving children was (52.4±28.6) months, and no mid- and long-term death occurred. Two patients underwent the third operations due to pulmonary restenosis. The multivariate analysis result showed that combined aortic arch surgery and early postoperative RVOT velocity>3 m/s were independent risk factors for mid- and long-term residual after ASO. Conclusion ASO is an ideal procedure for the treatment of D-TGA/IVS, D-TGA/VSD and Taussig-Bing malformations. Combined aortic arch surgery and early postoperative RVOT velocity>3 m/s are independent risk factors for mid- and long-term residual after ASO.

Objective:To analyze the impact of different intrauterine intervention methods and types of complications on fetal prognosis in cases of giant placental chorioangioma (CA), and determine the indications for various treatment methods by analyzing cases of adverse outcomes.Methods:Relevant articles were retrieved from China National Knowledge Infrastructure, VIP Database, Wanfang Database, and Yiigle using the keywords "placental chorioangioma" and "fetal edema" or "anemia" or "cardiomegaly" or "polyhydramnios," and from PubMed, Embase, and UpToDate databases using the keywords "placental chorionic angioma or chorioangioma" and "fetal edema" or "anemia" or "polyhydramnios" or "hyperdynamic circulation" up to June 30th 2023. The size of the angiomas, fetal complications, intrauterine intervention methods, gestational weeks at intervention, and pregnancy outcomes were analyzed. Fetal and neonatal deaths were defined as adverse outcomes. Statistical analysis was performed using an independent sample t-test, rank-sum test, or Chi-square test (continuity correction Chi-square test or Pearson Chi-square test). Results:(1) A total of 582 articles were retrieved, and 51 articles were finally included, comprising 65 cases. Based on the intrauterine intervention methods, these cases were divided into the symptomatic treatment group (17 cases) and the etiological treatment group (48 cases). There were no statistically significant differences between the two groups in the maximum diameter of the angiomas, the gestational weeks at intervention, or the gestational weeks at delivery. (2) The incidence of adverse outcomes was 3/17 in the symptomatic treatment group and 27.1% (13/48) in the etiological treatment group, with no statistically significant difference. In the etiological treatment group, the incidence of adverse outcomes in cases with fetal edema was 45.4% (10/22), which was significantly higher than the 11.5% (3/26) in cases without fetal edema, and the difference was statistically significant ( χ 2=6.94, P=0.008). (3) An analysis of 13 cases with adverse outcomes revealed that nine cases had highly vascularized chorioangiomas and/or blood supply vessels located close to the umbilical cord insertion point on the placenta, and nine were complicated by fetal edema. The incidence of adverse outcomes for fetoscopic laser coagulation/bipolar coagulation, radiofrequency or microwave ablation, bioglue embolization, anhydrous alcohol ablation, and microcoil embolization were 4/19, 3/4, 1/8, 2/9, and 3/6, respectively. Conclusions:Intrauterine treatment of CA should be individualized. Bioglue embolization may be the first-line treatment; Fetoscopic laser coagulation can be applied to cases where the blood supply vessels are small and superficial;Interstitial laser ablation and radiofrequency ablation can be used for branch-type CA when the main blood supply vessels are located within the hemangioma; Anhydrous alcohol ablation is contraindicated due to its risk of fetal circulation entry; Microcoil embolization has the risk of incomplete occlusion, which should be used with caution.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

Glucagonoma is a rare neuroendocrine tumor derived from the pancreatic α cells, and alopecia is an uncommon clinical manifestation. We report a case of glucagonoma presenting with marked alopecia, aiming to raise clinicians′ awareness of this rare presentation.

Objective To construct a quality control model for cervical liquid-based thin cell smears using two different artificial intelligence(AI)techniques and to compare the total use of the two methods to improve the level of quality control of cervical liquid-based thin cell smears through the assistance of hybrid AI.Methods In this study,105 cervical liquid-based thin cell smear samples were used.Convolutional neural network(CNN)algorithm and Transformer network algorithm were used as specific AI algorithms in the AI model.The labeled features included the number of cells in the slice,excessive red blood cells,excessive inflammatory cells,and air bubbles.The smear samples were pre-processed and digitized by smear,followed by image segmentation and feature extraction.Using the labeled feature data,machine learning models were trained and optimized.Statistical AI and physician QC results were analyzed by calculating KAPPA index,sensitivity,specificity,area under the curve(AUC),and other indexes for AI QC results.Results CNN algorithm QC results in normal smear,inflammatory background and bloody background were significantly different from the expert review QC results(P＜0.001).Transformer algorithm QC results were similar to the expert review results,with no statistical difference(P＞0.05).General practitioner QC results were statistically different from the expert review QC results in normal smear detection rate and bloody background(P＜0.001).CNN algorithm Kappa value was 0.567,which had medium consistency with expert review results.Transformer algorithm Kappa value was 0.890,with the best consistency with expert review results.General practitioner Kappa value was 0.675,which had better consistency with expert review results.Using the expert review results as a reference standard,the predictive efficacy of the Transformer algorithm and the general practitioners' QC results was evaluated,and the predictive efficacy of the Transformer algorithm was higher than that of the general practitioners in detecting hemorrhagic backgrounds and normal smears(inflammatory backgrounds:AUC=1.000;normal smears:AUC=0.768)(hemorrhagic backgrounds:AUC=0.849;normal smears:AUC=0.849;normal smear:AUC=0.500).Conclusion In this study,we found that the Transformer algorithm was effective in improving the quality control of cervical liquid-based thin-layer cell smears by assisting doctors to perform smear quality control scoring and improving the efficiency and accuracy of smear sample quality control.It can be used as a new quality control method for cervical cancer cytological screening and has potential clinical applications.