Objective To construct a lung cancer surgery-oriented disease-specific database covering the entire perioperative care pathway, thereby improving the quality and usability of key surgical data elements. Methods Real-world clinical data were extracted from a single-center thoracic surgery department. A standardized data model was established based on the open electronic health record (openEHR) standard. Large language model (LLM), optical character recognition (OCR), and artificial intelligence (AI)-driven techniques were employed to extract, structure, and perform quality control on unstructured clinical narratives, imaging reports, and radiological data, with a focus on capturing surgically relevant perioperative indicator. Results A multimodal database comprising 19 917 patients was established, including 7 930 males and 11 987 females, with ages ranging from 15 to 97 (61.7±9.7) years. The database includes 582 structured data variables, textual report data corresponding to 69 clinical indicators, 13 000 pulmonary function test PDF reports, and chest CT imaging data from 16 884 patients. This database comprehensively covers major information relevant to surgical diagnosis and treatment of lung cancer, significantly improving the completeness and granularity of surgical detail data. Large language models (LLMs) and optical character recognition (OCR) technologies enhanced the efficiency of converting unstructured data into structured formats, while a multi-level manual verification process ensured data accuracy and traceability. The database supports real-world research including comparisons of surgical procedures, prediction of postoperative complications, prognosis assessment, and multimodal data association analyses.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective To investigate the epidemiological characteristics of imported malaria cases in Shanghai Municipality from 2020 to 2024, so as to provide insights into dynamic adjustment of imported malaria control strategies. Methods All data pertaining to malaria cases reported in Shanghai Municipality from 2020 to 2024 were collected from Infectious Diseases Reporting Information Management System and Parasitic Diseases Prevention and Control Information Management System of Chinese Center for Disease Control and Prevention, and epidemiological investigation reports of malaria cases. The type of malaria cases, source of acquiring infections, temporal, spatial and population distributions of malaria cases, type of initial diagnosis institutions, accuracy of initial diagnosis, time interval from disease onset to initial diagnosis, and the time interval from initial diagnosis to diagnosis were statistically analyzed. The monthly distribution of malaria cases was analyzed using a circular distribution method. Results A total of 124 malaria cases were reported in Shanghai Municipality from 2020 to 2024, with 14, 52, 22, 8 and 28 cases annually, respectively, and all cases were overseas imported cases. Plasmodium falciparum malaria was the predominant type, accounting for 82.26% (102/124) of all malaria cases, while P. ovale, P. vivax and P. malariae malaria accounted for 8.06% (10/124), 7.26% (9/124) and 2.42% (3/124) of reported cases, respectively. Malaria cases acquired infections from 28 countries in 4 continents, with African countries as a major source of acquiring infections (96.77%, 120/124). Malaria cases were reported across all 16 districts in Shanghai Municipality. There were peaks in numbers of reported malaria cases in May 2021 (9 cases) and November 2021 (9 cases); however, there was no concentration trend in the reporting time of malaria cases from 2020 to 2024 (Z = 2.45, P > 0.05). The reported malaria cases included 116 males and 8 females, with a male-to-female ratio of 14.5∶1.0, and had a median age of 39 (17) years. Worker was the primary occupation of reported malaria cases, accounting for 48.39% (60/124) of all reported cases. City-level medical institutions were the predominant initial diagnosis institutions (75.81%, 94/124). The overall accuracy of initial diagnosis was 74.19% (92/124), and the median time interval from disease onset to initial diagnosis was 0 (2) day (healthcare seeking on the day of disease onset), with 72.58% (90/124) of malaria cases seeking healthcare services within one day. The median time interval from initial diagnosis to diagnosis was 2 (3) days, with 41.94% (52/124) of malaria cases that were definitively diagnosed within one day following initial diagnosis. There were significant differences in the accuracy of initial malaria diagnosis (χ² = 15.01, P < 0.05), the time interval from disease onset to initial diagnosis (H = 29.30, P < 0.001), and the time interval from initial diagnosis to diagnosis (H = 22.92, P < 0.001) among years from 2020 to 2024, and the time interval from disease onset to initial diagnosis (Z = -5.09, P < 0.001) and the time interval from initial diagnosis to diagnosis (Z = -4.14, P < 0.001) were both shorter during the period from 2020 to 2022 than those recorded from 2023 to 2024. In addition, a total of 2 malaria deaths were reported in Shanghai Municipality during the period from 2020 to 2024, both caused by P. falciparum malaria. Conclusions The numbers of malaria cases fluctuated continuously in Shanghai Municipality from 2020 to 2024. It is recommended to continuously strengthen surveillance and response measures, improve malaria diagnosis and treatment capabilities, and conduct targeted health education activities among high-risk populations, such as labors going to overseas malaria hyper-endemic areas, so as to prevent re-establishment of imported malaria.

Objective:To analyze transcranial sonography（TCS）imaging characteristics of rats with 6-hydroxydopamine hydrochloride（6-OHDA）and explore the correlations between the imaging characteristics with motor deficits and pathological changes.Methods:Twenty-nine male SD rats were divided into 3 groups：8 in the no-treatment control（NC）group，10 in the Sham group and 11 in the 6-OHDA group. The model for Sham/Parkinson's disease（PD）was established by stereotacticly injecting saline/6-OHDA containing ascorbic acid to bilateral substantia nigra pars compacta（SNpc）. After three weeks，the models were stable. At the fourth week and seventh week，the behavioral testing was accomplished. The TCS examination was performed weekly at the same time for four weeks. At the eighth week，the rats were sacrificed for pathology.Results:①Behavioral testing：6-OHDA group showed asymmetric motor deficits and the difference was significant compared with the NC group and Sham group（both P<0.001）. ②TCS examination：compared with the NC and Sham group，there were asymmetric substantia nigra hyperechogenicity（SNH）in 6-OHDA group（both P<0.05）；meanwhile the area of SNH in the left was significantly larger in the right side（ P<0.05）.No significant change in SNH area was found during the continuous observation period of weeks 4-7. For 6-OHDA group，the area of SNH was negatively correlated with the number of forelimb wall-touches（ r=-0.825， P＜0.001）. ③Pathological examination：compared with NC group and sham group，the substantia nigra（SN）of 6-OHDA group showed a series of pathological events，including dopaminergic（DA）neurons asymmetrically decreasing，asymmetric ironion deposition and the number of active microglia increasing（all P＜0.05）. Correlation analysis showed that the area of SNH was negatively correlated with the number of DA neurons survivors（ r=-0.689， P=0.013），while the activation of microglial and the deposition of iron were positively correlated with the area of SNH（ r=0.915，0.735；all P＜0.001）. Conclusions:Asymmetric SNH of 6-OHDA PD rats is a representation of asymmetric motor deficits，and the mechanism is related to a catalogue of asymmetric pathological changes in SN，which comprise DA neurons decreasing，asymmetric iron ions deposition，microglial activating.

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To explore the effectiveness of immersive virtual reality (VR)-guided core stability-assisted training in improving the balance of ischemic stroke survivors.Methods:Sixty-six hemiplegic ischemic stroke survivors were randomly divided into a conventional rehabilitation training group (CON) of 32 and an immersive VR-guided core stability-assisted training group (VR-TOT) of 34. In addition to basic internal medical treatment, the CON group underwent conventional rehabilitation therapy, while the VR-TOT group received VR-guided core stability-assisted training. Before and after 4 weeks of the treatments, the subjects′ balance was evaluated using the Fugl-Meyer balance scale. A three-dimensional force platform was used to collect the sway amplitude, sway speed, peripheral area and total trajectory length of the center of pressure COP of the bilateral plantar in the left-right and anterior-posterior directions while the subjects stood with the eyes open and closed.Results:After the treatments, the average Fugl-Meyer balance scores of both groups had improved significantly. In the eyes-open condition, after the treatment, there was a significant decrease in the average COP sway amplitude in the anteroposterior direction on the hemiplegic side among the CON group, as well as in both the mediolateral and anteroposterior directions on both sides in the VR-TOT group. The sway velocity in the anteroposterior direction on the hemiplegic side had decreased significantly in both groups, and the sway velocity in both the mediolateral and anteroposterior directions on the non-hemiplegic side had also decreased significantly. In the CON group the peripheral area on the non-hemiplegic side had decreased and the total trajectory length had shortened significantly. In the VR-TOT group there were significant decreases in the peripheral area on both sides and in the total trajectory length on both sides. Comparing the two groups after treatment, the peripheral area on the hemiplegic side in the VR-TOT group was significantly smaller. In the eyes-closed condition, the sway amplitude of the COP on the hemiplegic side in the anteroposterior direction and on the non-hemiplegic side in both the mediolateral and anteroposterior directions had decreased significantly in the VR-TOT group after the treatment. The average sway velocity had decreased significantly in the anteroposterior direction on the non-hemiplegic side in the CON group. In the VR-TOT group this was observed in the anteroposterior direction on the hemiplegic side and in both the mediolateral and anteroposterior directions on the healthy side. In the CON group the average peripheral area of the COP on the hemiplegic side had decreased, and the total trajectory length had shortened, both significantly. In the VR-TOT group, the peripheral area on the non-hemiplegic side had decreased significantly as well.Conclusions:Core stability-assisted training based on immersive virtual reality can effectively improve the balance of ischemic stroke survivors. It shows promise for clinical application.