Objective To investigate the palmitoyltransferase (PATs) activity during different developmental stages of Plasmodium falciparum and to explore the impact of PATs activity on intra-erythrocytic replication and gametocytogenesis, so as to provide insights into development of novel antimalarial targets. Methods The PATs activity was measured using the click chemistry method during different developmental stages of P. falciparum, including rings, trophozoites, schizonts, and gametocytes. P. falciparum-infected erythrocytes were divided into three groups, including a control group, a dimethyl sulfoxide (DMSO) group, and a 2-bromopalmitate (2-BP) group. Erythrocytes in the control group were incubated in normal culture media, and cells in DMSO and 2-BP groups were exposed to DMSO or 2-BP at a final concentration of 10 μmol/L to examine the inhibitory effect of 2BP on the PATs activity. The growth curve analysis and gametocyte production assay were employed to investigate changes in asexual proliferation and gametocyte production of P. falciparum following inhibition of the PATs activity with 2-BP, and transcriptomics sequencing was performed to examine the impact of inhibition of the PATs activity with 2-BP on transcriptional levels of P. falciparum and possible mechanisms. Results The green fluorescence intensity of PATs varied across developmental stages of P. falciparum (F = 38.120, P < 0.001), with a higher fluorescence intensity seen in trophozoites (35.680 ± 8.439), merozoites (33.380 ± 9.030) and gametocytes (21.540 ± 8.654), and a lower intensity in ring bodies (10.720 ± 3.183) (all P values < 0.05). The green fluorescence intensities were 8.738 ± 1.576, 8.633 ± 1.827 and 4.911 ± 0.318 in the control group, DMSO group, and 2-BP group 4 days post-culture (schizont stage), respectively (F = 91.490, P < 0.001), and the PATs activity was significantly inhibited post-treatment with 2-BP (P < 0.05). The areas under the time curve for the parasitemias were 25.700 ± 0.696, 28.630 ± 3.062 and 8.370 ± 1.751 in the control group, DMSO group, and 2-BP group following inhibition of the PATs activity during the asexual stage of P. falciparum (F = 83.440, P < 0.001), and the parasitemia was lower in the 2-BP group than in the control group and the DMSO group (both P values < 0.001). In addition, the asexual stage development was delayed in the 2BP group, with abnormal morphology seen. The numbers of merozoites were 18.050 ± 4.362, 18.200 ± 3.517 and 14.020 ± 4.320 in each schizont in the control group, DMSO group and 2-BP group, respectively (H = 39.100, P < 0.001), and the merozoite number was significantly lower in the 2-BP group than in the control group and the DMSO group (both P_adjusted values < 0.001). The areas under the time curve for P. falciparum gametocyte production were 18.900 ± 0.384, 18.240 ± 0.177 and 7.507 ± 0.201 in the control group, the DMSO group, and the 2-BP group following inhibition of the PATs activity, respectively (F = 1 677.000, P < 0.001), and the proportion of gametocyte production was statistically lower in the 2-BP group than in the control group and DMSO group (both P values < 0.001). The formation and maturation of gametophytes were blocked in the 2-BP group, and most of them were arrested in the middle and late stages. Following 2-BP treatment, significantly down-regulated genes during the asexual stage of P. falciparum were significantly enriched in cell cycle regulation, mitosis, DNA damage/response and structural organization, and significantly down-regulated genes during the gametocyte stage were significantly enriched in biological processes of cell cycle (mitosis and G1/S transition), RNA regulation and metabolism (such as carbon catabolite repression 4-negative on TATA-less) and cell development and differentiation. Conclusion The palmitoylation modification plays an important role in the asexual reproduction and gametocyte generation and development of P. falciparum.

Objective Based on the needs of supportive care,a supportive care program for patients treated with lymphoma chimeric antigen receptor T cell(CAR-T)immunotherapy was constructed.Methods A questionnaire for supportive care program was initially constructed through a literature review and semi-structured interviews,and then refined through two rounds of Delphi method.Results The response rates for two rounds of questionnaires were both 100％.The expert authority coefficients were 0.89 and 0.90 respectively,and the Kendall's coefficient of concordance was 0.253 and 0.262 respectively.The final program included five primary categories(health information support,physiological symptoms and daily living support,psychological support,care and emotional support,and safety support),20 secondary categories,and 50 tertiary categories.Conclusion The supportive care program developed in this study for patients receiving CAR-T immunotherapy for lymphoma has certain scientific and feasibility.

Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

Objective:To explore the potential value of dynamic changes of inflammatory factors in evaluating the efficacy of platinum regimen in the first-line treatment of advanced lung adenocarcinoma(LUAD).Methods:A total of 121 patients with advanced LUAD without common target mutations who were admitted to Dongtai People's Hospital to receive first-line treatment with platinum regimen from January 2021 to January 2023 were selected,and relevant clinical data such as general information,hematuria routine,angiogenic factors,serum tumor markers,inflammatory factors,immunoglobulin and T lymphocyte indexes were collected and statisti-cally analyzed.Patients in complete response(CR)group and partial response(PR)group were classified as chemotherapy sensitive group;stable(SD)group and progressive(PD)group were classified as chemotherapy insensitive group according to response evaluation criteria in solid tumors(RECIST).Through univariate and multi-factor Logistics regression analysis,the influencing factors of first-line treatment efficacy of platinum regimen in patients with advanced LUAD were analyzed,and the regression equation y=1-1/(1+e-z)prediction model was established and verified.Receiver operating characteristic(ROC)curve was used to analyze the potential value of dynamic changes of inflammatory factors in evaluating the efficacy of platinum-based first-line treatment for advanced LUAD.Results:①Univariate and multivariate Logistic regression analysis showed that CEA,TNF-α,IL-6,IL-8,IL-18,IL-1β and hs-CRP were still the influencing factors for the efficacy of first-line chemotherapy of platinum regimen in patients with advanced LUAD(P<0.05).②Inflammatory factors TNF-α,IL-6,IL-8,IL-18,IL-1β and hs-CRP were included in multivariate Logistic regression analysis.After correcting confounders(Model 5),high levels of TNF-α,IL-6,IL-8,IL-18,IL-1β and hs-CRP were positively correlated with insensitivity after first-line chemotherapy of platinum regimen in advanced LUAD patients(P<0.05).Restrictive cubic spline model analysis showed that the dynamic changes of inflammatory factors and the insensitivity of patients with advanced LUAD after first-line chemotherapy all had a nonlinear dose-response relationship.With the increases of TNF-α,IL-6,IL-8,IL-18,IL-1β and hs-CRP levels,patients with advanced LUAD have a greatly increased risk of desensitization after first-line chemotherapy.③Stratified interaction test analysis showed that tumor stage,differentiation degree and lymph node metastasis before and after correction factors were significantly correlated with expressions of inflammatory factors(all P<0.05,all P interaction<0.05).④Prediction model based on the influence factors of inflammatory factors was well distinguished and accurate,the area under ROC curve(AUC)before and after internal validation for detecting chemotherapy sensitivity in patients with advanced LUAD treated with platinum regimen first-line therapy was 0.87(95%CI:0.81～0.93)and 0.88(95%CI:0.82～0.95),respectively,and the sensitivity were 89.69%and 89.75%,respectively,the specificity were 91.77%and 91.85%,respectively.Conclusion:Dynamic changes of inflammatory factors is an important factor affecting the chemotherapy efficacy of patients with advanced LUAD treated with platinum-containing regimen.With the significant decrease of inflammatory factors,the sensitivity of patients to chemotherapy is also significantly increased.

Objective:To establish three machine learning prediction models based on CT imaging characteristics of papillary thyroid carcinoma (PTC) , and use SHAP (shapley additive explanations) analysis to investigate the contribution of each CT image features in the best model.Methods:CT imaging features in 426 cases of 440 PTCs confirmed pathologically from Jan. 2016 to Jan. 2021 at the affiliated Hangzhou First People’s Hospital of Westlake University Medical School were retrospectively analyzed. compared with 467 cases of 528 nodular goiter (NG) , evaluating the distribution of four CT characteristics: cookie bite sign, enhanced range of narrowing/blur (ERNB) , microcalcifications, and irregular shape. We split the data into 8∶2 ratio for training and testing sets, then constructed three machine learning models using XGBoost, RF, and SVM. Based on AUC, accuracy, F1 score, and other metrics, we selected the best model. Lastly, we used SHAP values to assess each CT feature’s contribution and positive/negative effects on the model.Results:Among 440 PTC and 528 NG nodules, CT features like cookie bite sign, ERNB, microcalcifications, and irregular shape occurred in 326 and 30 ( χ 2=483.05, P<0.001) , 363 and 106 ( χ 2=374.45, P<0.001) , 158 and 53 ( χ 2=94.24, P<0.001) , and 354 and 52 ( χ 2=491.34, P<0.001) nodules, respectively. The machine learning models built using XGBoost, RF, and SVM had AUC, accuracy, and F1 scores ranging from 0.884~0.925, 0.867~0.873, and 0.844~0.854 respectively on the training set. On the test set, the scores ranged from 0.869~0.923, 0.845~0.871, and 0.803~0.845. Among them, the XGBoost model demonstrated the highest diagnostic performance on the test set. Among the four CT features, irregular shape had the highest absolute SHAP value, positively contributing to PTC diagnosis. Conclusion:XGBoost model showed the highest PTC diagnostic performance. Irregular shape had the greatest positive impact on PTC diagnosis.

Objective Based on the needs of supportive care,a supportive care program for patients treated with lymphoma chimeric antigen receptor T cell(CAR-T)immunotherapy was constructed.Methods A questionnaire for supportive care program was initially constructed through a literature review and semi-structured interviews,and then refined through two rounds of Delphi method.Results The response rates for two rounds of questionnaires were both 100％.The expert authority coefficients were 0.89 and 0.90 respectively,and the Kendall's coefficient of concordance was 0.253 and 0.262 respectively.The final program included five primary categories(health information support,physiological symptoms and daily living support,psychological support,care and emotional support,and safety support),20 secondary categories,and 50 tertiary categories.Conclusion The supportive care program developed in this study for patients receiving CAR-T immunotherapy for lymphoma has certain scientific and feasibility.

ObjectiveTo explore the central neuroregulation mechanism of heat-sensitive moxibustion for knee osteoarthritis on pain relief. MethodsThirty patients who did not have experience of Deqi （得气） during heat-sensitive moxibustion treatment were assigned to the "non-Deqi group"， while another 30 patients who had experience of Deqi were assigned to the "Deqi group". Both groups received moxibustion at the left Heding （EX-LE2） acupoint. In the Deqi group， after the patients experienced sensation of Deqi at the acupoint， moxibustion was applied at approximately 3 cm from the skin for 10 minutes； in the non-Deqi group， moxibustion was also applied at approximately 3 cm from the skin for 10 minutes. Both groups received treatment once daily for 10 consecutive days. Knee joint pain was assessed before and after treatment using the visual analog scale （VAS）. Resting-state functional magnetic resonance imaging （rs-fMRI） scans were performed on all participants before the first treatment session and after the final session on the 10th day. The fractional amplitude of low-frequency fluctuations （fALFF） maps before and after treatment were processed using the SPM12 module by MATLAB. ResultsAfter treatment， VAS scores in both groups were significantly lower than before treatment （P＜0.05 or P＜0.01）， with the Deqi group showing significantly lower VAS scores than the non-Deqi group （P＜0.01）. Compared to before treatment， the Deqi group exhibited significant activation in the prefrontal cortex （t = 6.28）， white matter （t = 6.36）， and left temporal lobe （t = 9.33）， while significant inhibition was observed in the occipital lobe （t = -9.86） and right cerebrum （t = -4.54， P＜0.01）； in the non-Deqi group， significant changes after treatment were observed in the left occipital lobe （t = -6.42）， left medial frontal gyrus （t = -4.35）， left middle frontal gyrus （t = -4.74）， right superior frontal gyrus （t = -4.82）， right superior temporal gyrus （t = -6.61）， and right cerebellar posterior lobe （t = -8.64）， all of which were in inhibited states （P＜0.01）. Compared to the non-Deqi group， the Deqi group exhibited significant activation after treatment in the external nucleus （t = 5.77）， white matter （t = 3.58）， right cerebrum （t = 5.84）， left cerebellum （t = 5.35）， and left cerebrum （t = 4.32）， while significant inhibition was observed in the prefrontal cortex （t = -4.16）， occipital lobe （t = -4.87）， and precentral gyrus （t = -4.46， P＜0.01）. ConclusionsHeat-sensitive moxibustion provides better analgesic effects for knee osteoarthritis under state of Deqi. Its central neuroregulation mechanism may be related to the involvement of the frontal lobe， temporal lobe， occipital lobe， external nucleus， white matter， right cerebrum， left cerebellum， left cerebrum， and precentral gyrus in modulating pain signals.

ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

Objective To investigate the safety and effectiveness of endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO)over 24 h after onset.Methods The clinical data of AIS-LVO patients who received endovascular treatment in Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2022 were retrospectively analyzed,including baseline characteristics,imaging findings,treatment,degree of vascular recanalization(modified thrombolysis in cerebral infarction grade 2b and 3 for successful recanalization)and prognosis.Results A total of 57 patients were included,including 42 males and 15 females,aged from 30 to 84 years old.The most common risk factors were hypertension(39 cases,68.4%),followed by smoking history(24 cases,42.1%),diabetes mellitus(17 cases,29.8%),previous stroke history(16 cases,28.1%),and atrial fibrillation(9 cases,15.8%).Before treatment,the National Institutes of Health stroke scale score was 12.84±7.04,and the Alberta Stroke Program early computed tomography score was 9.00(7.00,10.00).Vascular occlusion sites included middle cerebral artery occlusion in 27(47.4%)cases,internal carotid artery occlusion in 24(42.1%)cases,and tandem lesions in 6(10.5%)cases.The time from onset to femoral artery puncture was 38.30(28.17,53.71)h,and the time from femoral artery puncture to vascular recanalization was 52.00(38.50,92.50)min.General anesthesia was the main anesthesia method,accounting for 64.9%(37/57).The etiological types of stroke were mainly large artery atherosclerosis(38 cases,66.7%),cardiogenic embolism(9 cases,15.8%),unknown causes(6 cases,10.5%),and other clear causes(4 cases,7.0%).Mechanical thrombectomy was the first choice in 41(71.9%)cases,balloon dilatation/stenting was used in 35(61.4%)cases,of which 15(26.3%)cases were the first choice.Finally,53(93.0%)cases were recanalized successfully.In terms of complications,1(1.8%)case had symptomatic intracranial hemorrhage.The 90-d prognosis rate was 59.6%(34/57),and 3(5.3%)cases died.Conclusion Endovascular treatment for AIS-LVO patients over 24 h after onset has high recanalization rate and good safety,but it still needs to be further verified by randomized controlled trials.

Objective:To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (T1D).Methods:This was a retrospective case series study of clinical data from 24 patients with ICI-T1D admitted to People′s Hospital of Henan Provincial between January 2018 and December 2024. The data collected included demographic characteristics, ICI usage, clinical manifestations, laboratory test results, and clinical outcome. Patients were categorized into mild and severe groups based on disease severity. Clinical characteristics between the two groups were compared using the Mann-Whitney U test. Results:Of the 24 patients, 21 (87.5%) were male and 3 (12.5%) were female, with an average age of (62.0±10.6) years. Patients in the severe disease group were significantly older than those in the mild disease group [(68.0±9.5) years vs. (58.4±9.8) years, P<0.05]. Compared to patients with mild disease, those with severe disease had significantly higher rates of impaired consciousness (9/9 vs.2/15), shorter ICI treatment cycles [3 (2, 6) vs. 6 (5, 8)], shorter time from ICI initiation to diabetes diagnosis [68 (31, 168) d vs. 162 (135, 235) d], and shorter time from the onset of diabetes symptoms to medical consultation [4 (2, 5) d vs. 8 (4, 26) d] (all P<0.05). The severe disease group also showed significantly higher blood glucose levels [43.0 (39.1, 57.3) mmol/L vs. 24.6 (19.6, 29.6) mmol/L] and a lower glycated hemoglobin level [6.8% (6.3%, 7.6%) vs. 7.9% (7.6%, 8.6%)], along with a higher incidence of fulminant T1D (8/9 vs. 2/15, all P<0.05). All patients received insulin injection therapy. After discharge, fasting C-peptide levels in 3 patients with mild disease showed a transient increase to 0.26, 0.43, 0.49 nmol/L but declined again after six months. Conclusions:ICI-T1D is characterized by acute onset and rapid progression. Older patients are more likely to develop severe disease. All patients require insulin therapy.