OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Purpose: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. Materials and Methods: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. Results: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes. Conclusions GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.

Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

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.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

This study was aimed at understanding the prevalence and influencing factors of food-borne parasitic diseases in ethnic minority areas of Guizhou Province,to provide a scientific basis for the development of appropriate intervention measures based on the human-animal-environment One Health concept.In 2023,the infection status of the human population,reservoir hosts,intermediate hosts,food-borne parasitic diseases,and related social and environmental factors were investigated in Congjiang County in Qidongnan Miao and Dong Autonomous Prefecture;Luodian County in Qiannan Buyi and Miao Autonomous Prefecture;and Ceheng County in Qianxinan Buyi and Miao Autonomous Prefecture.At least 1 000 individuals were sampled from each county,along with at least 50 insect-protected host samples from each location.Food-borne parasite infections were detected with the modified Kato thick smear method.A questionnaire survey was administered to the population.Detection of food-borne parasitic metacercariae was performed in intermediate host fish through the flaking and digestion method,and in crabs through the pounding and sedimentation method.The chi-square test was used to compare rates,and logistic regression was applied for multivariate analysis.A total of 3 023 questionnaires and fecal samples were collected.Males accounted for 47.50%,females accounted for 52.50%,and members of ethnic minorities accounted for 96.06%.A total of 186 food-borne parasitic infections were identified,and the infection rate was 6.15%.Five insect species were detected,which showed an infection rate of 5.39%.The infection rate of Clonorchis sinensis was 0.33%,that of Taenia was 0.40%,that of Heteroceles was 0.17%,that of Acanthus was 0.17%,and that of Echinostoma was 0.03%.Human infections with Echinostomus colloides and Echinostomia transferoris had not previously been reported in China.Single-factor analysis revealed statistically significant differences in food-borne parasite infections according to various factors,including the consumption of untreated water,raw fish and shrimp,raw pig blood,raw cow gastric juice,and raw pork and beef,as well as raw pig and cow viscera(P<0.05).Multivariate analysis indicated that the risk factors for food-borne parasite infections among residents in minority areas of Guizhou Province included the consumption of raw pig blood(OR=2.841,95%CI:1.809-4.463),raw cow gastric juice(OR=2.122,95%CI:1.297-3.469),and raw fish and shrimp(OR=1.779,95%CI:1.049-3.018).A total of 173 fecal samples of the reservoir host were examined,which showed a rate of food-borne parasite infection of 5.2%.A total of 510 intermediate host fish were examined,which showed a 4.51%positivity rate of encysted metacercaria of Clonorchis sinensis.The crab,pig,and beef samples were not positive.In conclusion,food-borne parasitic infections were prevalent in ethnic minority regions of Guizhou Province,and consumption of raw food were influencing factors.A focus on populations with raw food consumption habits,including raw pig blood,cow gastric juice,fish and shrimp,is essential.Concurrently,monitoring of animal hosts must be strengthened to perform key interventions according to the One Health concept.

OBJECTIVE To investigate the effect of N-methyl-D-aspartic acid(NMDA)receptor in the secondary visual cortex(V2)on methamphetamine-associated contextual learning and memory.METHODS With male C57BL/6J mice as subjects and using the mouse conditioned place preference(CPP)experiment,the scores of CPP were observed after microinjection of NMDA receptor selective antagonist D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase,single microinjec-tion of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,and methamphetamine(0.5 mg·kg-1,ip)-induced reactivation test and methamphetamine-associated contextual-induced reacti-vation test,to evaluate the effect of NMDA receptors on the formation,expression and reinstatement of methamphetamine-induced CPP.RESULTS Compared with the control group,microinjection of D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase did not have significant inhibitory effect on CPP scores,nor did single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to metham-phetamine(0.5 mg·kg-1,ip)-induced reactivation test or single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to methamphetamine-associated contextual-induced reactivation test.CONCLU-SION The NMDA receptor in the V2 is not involved in the formation,expression and reactivation of meth-amphetamine-associated contextual learning and memory.

OBJECTIVE To investigate the effect of N-methyl-D-aspartic acid(NMDA)receptor in the secondary visual cortex(V2)on methamphetamine-associated contextual learning and memory.METHODS With male C57BL/6J mice as subjects and using the mouse conditioned place preference(CPP)experiment,the scores of CPP were observed after microinjection of NMDA receptor selective antagonist D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase,single microinjec-tion of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,and methamphetamine(0.5 mg·kg-1,ip)-induced reactivation test and methamphetamine-associated contextual-induced reacti-vation test,to evaluate the effect of NMDA receptors on the formation,expression and reinstatement of methamphetamine-induced CPP.RESULTS Compared with the control group,microinjection of D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase did not have significant inhibitory effect on CPP scores,nor did single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to metham-phetamine(0.5 mg·kg-1,ip)-induced reactivation test or single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to methamphetamine-associated contextual-induced reactivation test.CONCLU-SION The NMDA receptor in the V2 is not involved in the formation,expression and reactivation of meth-amphetamine-associated contextual learning and memory.

This study was aimed at understanding the prevalence and influencing factors of food-borne parasitic diseases in ethnic minority areas of Guizhou Province,to provide a scientific basis for the development of appropriate intervention measures based on the human-animal-environment One Health concept.In 2023,the infection status of the human population,reservoir hosts,intermediate hosts,food-borne parasitic diseases,and related social and environmental factors were investigated in Congjiang County in Qidongnan Miao and Dong Autonomous Prefecture;Luodian County in Qiannan Buyi and Miao Autonomous Prefecture;and Ceheng County in Qianxinan Buyi and Miao Autonomous Prefecture.At least 1 000 individuals were sampled from each county,along with at least 50 insect-protected host samples from each location.Food-borne parasite infections were detected with the modified Kato thick smear method.A questionnaire survey was administered to the population.Detection of food-borne parasitic metacercariae was performed in intermediate host fish through the flaking and digestion method,and in crabs through the pounding and sedimentation method.The chi-square test was used to compare rates,and logistic regression was applied for multivariate analysis.A total of 3 023 questionnaires and fecal samples were collected.Males accounted for 47.50%,females accounted for 52.50%,and members of ethnic minorities accounted for 96.06%.A total of 186 food-borne parasitic infections were identified,and the infection rate was 6.15%.Five insect species were detected,which showed an infection rate of 5.39%.The infection rate of Clonorchis sinensis was 0.33%,that of Taenia was 0.40%,that of Heteroceles was 0.17%,that of Acanthus was 0.17%,and that of Echinostoma was 0.03%.Human infections with Echinostomus colloides and Echinostomia transferoris had not previously been reported in China.Single-factor analysis revealed statistically significant differences in food-borne parasite infections according to various factors,including the consumption of untreated water,raw fish and shrimp,raw pig blood,raw cow gastric juice,and raw pork and beef,as well as raw pig and cow viscera(P<0.05).Multivariate analysis indicated that the risk factors for food-borne parasite infections among residents in minority areas of Guizhou Province included the consumption of raw pig blood(OR=2.841,95%CI:1.809-4.463),raw cow gastric juice(OR=2.122,95%CI:1.297-3.469),and raw fish and shrimp(OR=1.779,95%CI:1.049-3.018).A total of 173 fecal samples of the reservoir host were examined,which showed a rate of food-borne parasite infection of 5.2%.A total of 510 intermediate host fish were examined,which showed a 4.51%positivity rate of encysted metacercaria of Clonorchis sinensis.The crab,pig,and beef samples were not positive.In conclusion,food-borne parasitic infections were prevalent in ethnic minority regions of Guizhou Province,and consumption of raw food were influencing factors.A focus on populations with raw food consumption habits,including raw pig blood,cow gastric juice,fish and shrimp,is essential.Concurrently,monitoring of animal hosts must be strengthened to perform key interventions according to the One Health concept.

Objective:To investigate the clinical management,complications,and prognostic prediction model of bronchopulmonary dysplasia(BPD)in preterm infants.Methods:A total of 854 very preterm infants(gestational age ≤ 32 weeks)admitted to the Neonatal Intensive Care Unit(NICU)of Shanghai Children's Hospital from January 2018 to December 2022 were retrospectively enrolled.After applying inclusion and exclusion criteria,713 infants were included.Based on the 2018 National Institute of Child Health and Human Development(NICHD)diagnostic criteria for BPD,the cohort was divided into a BPD group(n=164)and a non-BPD group(n=549).Clinical data of infants and maternal characteristics were compared between groups.Univariate and stepwise multivariate logistic regression analyses were performed to identify independent risk factors for BPD and evaluate clinical management.A nomogram model was subsequently developed to predict BPD prognosis.Results:Gestational age,duration of non-invasive ventilation,total oxygen therapy time,total hospital stay,hemodynamically significant patent ductus arteriosus(hsPDA),maximum diameter of patent ductus arteriosus(PDA),fetal growth restriction(FGR),use of vasoactive agents,and proportion of pulmonary surfactant administration were identified as independent risk factors for BPD(all P＜0.05,OR＞0).The nomogram model demonstrated excellent predictive performance,with an area under the receiver operating characteristic curve(AUC)of 0.93 and a calibration curve slope approaching 1.The Hosmer-Lemeshow goodness-of-fit test indicated satisfactory model calibration(x2=8.2865,P=0.406).Conclusion:Gestational age,non-invasive ventilation duration,total oxygen therapy time,total hospital stay,hsPDA,PDA maximum diameter,FGR,vasoactive agents,and pulmonary surfactant use are critical predictors of BPD in preterm infants.The prognostic models for BPD incidence and severity,constructed based on these factors,exhibit strong predictive accuracy and may serve as a valuable clinical tool for risk stratification and early intervention.