ObjectiveTo evaluate the detection specificity for clinical samples and the detection capability for standard substances of five commercially available multiplex polymerase chain reaction (PCR) nucleic acid detection kits (hereinafter referred to as the kits) for respiratory pathogens, and to provide a reference for selecting appropriate detection kits for multi-pathogen nucleic acid testing of respiratory infections. MethodsA total of 60 respiratory pathogen-positive clinical samples with known redults were selected and tested using the five kits (labeled as A, B, C, D, and E). The detection rates and Kappa coefficients were calculated to evaluate the consistency between the results from these kits and those from single-pathogen PCR kits. According to the limit of detection (LOD) provided by the kits, standard substances of respiratory pathogens (including 12 types such as influenza virus, Mycoplasma pneumoniae, and Bordetella pertussis) were diluted to four concentrations (250, 500, 1 000, and 2 000 copies·mL⁻¹). All five kits were used for detection to evaluate their respective detection capabilities. ResultsCompared with the results from single-pathogen PCR kits, the five tested kits demonstrated good consistency (all Kappa >0.80). Among them, Kit A had the highest detection rate (100.00%), followed by Kits C and E (98.33%), and then Kits B and D (95.00%). All five kits showed a relatively low false negative rate (FNR) for samples with a cycle threshold (Ct) value ≤35 (≤2.38%). However, for samples with Ct values>35, the FNR increased accordingly(average FNR=6.67%, P=0.029). Kit C exhibited the highest detection sensitivity for the tested standard substances (average LOD: 458.33 copies·mL⁻¹), followed by Kit D, then Kits A/E, and finally Kit B. ConclusionThe five multiplex PCR kits showed good consistency with single-pathogen detection results, but each had its own performance emphasis. Kit A, with the highest detection rate and high throughput, is suitable for targeted viral screening. Kit B, covering the broadest pathogen spectrum (including fungi/bacteria), is suitable for comprehensive respiratory pathogen screening. Kits C, D and E, are applicable for rapid detection. It is important to note that the detection efficacy of all kits decreases for low viral load samples with Ct values >35. In practical application, selection should be based on specific screening objectives, throughput requirements, and sample types.

OBJECTIVE To analyze the efficacy and safety of luspatercept in the treatment of myelodysplastic syndromes （MDS） anemia， and provide reference for clinical medication. METHODS The literature related to luspatercept for MDS anemia in PubMed， Cochrane Library， Embase and Web of Science were searched by computer， and the search time was from the establishment of the database to January 2024. The quality of literature was evaluated after they were screened according to inclusion and exclusion criteria， the single-group rate meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software， and the subgroup analysis was conducted. RESULTS A total of 756 patients in 9 articles were included in this study. The results of meta-analysis showed that the proportion of MDS patients who reached ≥8 weeks of red blood cell transfusion independence （RBC-TI） was 46% after using luspatercept [95%CI （0.28， 0.64）， P＜0.000 01]. The proportion of MDS patients whose hematological improvement in erythrocyte （HI-E） was 59% [95%CI （0.43， 0.74）， P＜0.000 01]. Among them， 5 articles reported that the proportion of MDS patients with grade 3-4 adverse reactions was 14% [95%CI （0.07， 0.22）， P＝0.000 2]， and the poor general condition， infection， blood and lymphatic system disease were the common adverse reactions. Subgroup analysis showed that the source of heterogeneity was the blood transfusion burden in the proportion of MDS patients with RBC-TI≥8 weeks， and the source of heterogeneity was the 0931-8356251。revised international prognostic scoring system （IPSS-R） risk grade， SF3B1 mutation status and blood transfusion burden in the proportion of MDS patients with HI-E. Sensitivity analysis showed that the results of this study were stable. CONCLUSIONS Luspatercept can significantly improve blood transfusion dependence， reduce blood transfusion burden and promote hematology improvement in MDS patients. But attention should be paid to the occurrence of grade 3-4 adverse events； adverse events such as poor general condition， infection， blood and lymphatic system diseases are more common.

Objective To evaluate the effectiveness of the integrated schistosomiasis control programme in Wuhan City from 2005 to 2023, so as to provide insights into precision control and elimination of schistosomiasis. Methods The integrated measures for schistosomiasis control implemented by health, agriculture, water resources, and forestry departments of Wuhan City, and the epidemiological data of schistosomiasis in Wuhan City were collected from 2005 to 2023, and the prevalence of human schistosomiasis, prevalence of Schistosoma japonicum infections in humans and bovines, areas of S. japonicum-infected snail habitats, areas of snail habitats in inner embankments, and actual areas of snail habitats were retrieved. In addition, the trends in prevalence of schistosomiasis in humans and livestock and snail status were evaluated in Wuhan City from 2005 to 2023 using Mann-Kendall test and a Joinpoint regression model. Results Mann-Kendall test revealed a tendency towards a decline in the prevalence of human schistosomiasis (Z = -4.41, P < 0.01), prevalence of S. japonicum infections in humans (Z = -4.89, P < 0.01) and bovines (Z = -4.50, P < 0.01), areas of S. japonicum-infected snail habitats (Z = -3.91, P < 0.01), areas of snail habitats in inner embankments (Z = -2.28, P = 0.02), and actual areas of snail habitats (Z = -5.95, P < 0.01) in Wuhan City from 2005 to 2023. Joinpoint regression analysis showed an average annual reduction of 8.58% in the prevalence of human schistosomiasis in Wuhan City from 2005 to 2023 [average annual percent change (AAPC) = -8.58%, 95% confidence interval (CI): (-10.02%, -6.65%), P < 0.01], with two joinpoints in 2013 and 2016, respectively, and the tendency towards a decline showed statistical significance during the period from 2013 through 2016 [annual percent change (APC) = -34.41%, 95% CI: (-40.36%, -20.01%), P < 0.01]. The prevalence of S. japonicum human infections appeared an average annual reduction of 51.91% in Wuhan City from 2005 to 2023 [AAPC = -51.91%, 95% CI: (-58.12%, -44.25%), P < 0.01], with two joinpoints in 2014 and 2017, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.17%, 95% CI: (-99.17%, -90.87%), P < 0.01]. The prevalence of S. japonicum infections in bovines appeared an average annual reduction of 53.12% in Wuhan City from 2005 to 2023 [AAPC = -53.12%, 95% CI: (-59.65%, -42.44%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.63%, 95% CI: (-99.44%, -90.93%), P < 0.01]. The areas of S. japonicum-infected snail habitats appeared an average annual reduction of 47.09% in Wuhan City from 2005 to 2023 [AAPC = -47.09%, 95% CI: (-52.92%, -38.26%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2011 through 2014 [APC = -97.27%, 95% CI: (-98.65%, -88.06%), P < 0.01]. The areas of snail habitats in inner embankments appeared an average annual reduction of 4.45% in Wuhan City from 2005 to 2023 [AAPC = -4.45%, 95% CI: (-5.18%, -3.82%), P < 0.01], with three joinpoints in 2011, 2015 and 2018, respectively, and statistical significance was seen in the tendency towards a decline during the period from 2005 through 2011 [APC = -16.38%, 95% CI: (-20.15%, -14.25%), P < 0.01]. In addition, the actual areas of snail habitats appeared an average annual reduction of 2.65% in Wuhan City from 2005 to 2023 [AAPC = -2.65%, 95% CI: (-2.89%, -2.40%), P < 0.01], with a joinpoint in 2013, and the tendency towards a decline showed statistical significance during the period from 2013 through 2023 [APC = -4.06%, 95% CI: (-4.66%, -3.58%), P < 0.01]. Conclusions The integrated schistosomiasis control programme achieved significant effectiveness in Wuhan City from 2005 to 2023, with a tendency towards a decline in morbidity due to schistosomiasis in humans and livestock and snail status. The integrated schistosomiasis control strategy with emphasis on management of the source of S. japonicum infections should continue to be implemented to consolidate the schistosomiasis control achievements and achieve the goal of schistosomiasis elimination in the city.

Objective To investigate the impact of nucleophosmin 1-mutated(NPM1m)subtypes,variant allele frequency(VAF)and co-mutations on the survival outcomes of patients with acute myeloid leukemia(AML).Methods Clinical data,mutation status,and outcomes of 86 NPM1m-AML patients admitted in Department of Hematology,First Hospital of Lanzhou University between June 2017 and September 2024 were collected and retrospectively analyzed.Spearman correlation analysis,Kaplan-Meier curve analysis,Log-rank test,and Cox regression analysis was applied for correlation analysis,survival analysis,and factors affecting survival.Results The overall survival(OS)was significantly shorter in the Rares subtype of NPM1m than the ABD subtype(median OS:164 d vs 416 d,P=0.043).The VAF of NPM1m was positively correlated with the initial peripheral blood white blood cell count and lactate dehydrogenase(LDH)level(P<0.05).OS was reduced when VAF was≥0.37(median OS:164 d vs 730 d,P=0.003).The presence of myelodysplasia-related gene(MR)mutations was associated with a poorer prognosis when compared to the MR wild-type(median OS:45 d vs 395 d,P<0.001).The triple mutation of FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)and DNMT3A also indicated a worse prognosis than the non-triple mutation(median OS:173 d vs 483 d,P=0.007).The presence of PTPN11 mutations was associated with improved OS(median OS:395 d vs 240 d,P=0.027),while the patients with coexistence of N/KRAS mutations trended toward better prognosis than the wild-type patients(median OS:662 d vs 189 d)though no statistical significance(P=0.070).Multivariate analysis revealed that LDH(HR=1.002,95%CI:1.000～1.003,P=0.005),NPM1m VAF(HR=2.415,95%CI:1.208～4.829,P=0.013),Rares subtype(HR=3.037,95%CI:1.134～8.136,P=0.027),and MR mutations(HR=5.283,95%CI:1.991～14.017,P<0.001)were independent risk factors associated with OS in the patients.Conclusion Molecular heterogeneity of NPM1m should be taken into account in prognostic stratification of NPM1m-AML.Factors including the Rares subtype,VAF≥0.37,coexistence of FLT3-ITD and DNMT3A mutations,and MR mutations are associated with poor prognosis of NPM1m-AML.The presence of PTPN11 mutations improves the prognosis,while the presence of N/KRAS mutations shows a trend toward better prognosis.LDH,NPM1m VAF,Rares subtype,and MR mutations are independent risk factors affecting OS of patients with NPM1m-AML.

Objective:To investigate the value of Sequential Organ Failure (SOFA) score and its dynamics (ΔSOFA) in predicting mortality in hematology care unit (HCU) .Methods:A retrospective clinical study was conducted on 79 critically ill hematologic patients admitted to the Center for Critical Care Medicine, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between May and June 2024. SOFA scores and ΔSOFA were calculated within 2 days before and after HCU admission. The predictive value of SOFA and ΔSOFA in mortality was assessed using receiver operating characteristic (ROC) curve analysis.Results:Among the 79 patients, the HCU mortality rate was 54.4%. The SOFA scores on days 1–3 (D1, D2, and D3) and ΔSOFA on day 1 (ΔD_1) of all patients, leukemia patients and hematopoietic stem cell transplantation (HSCT) patients were significantly higher in the death group compared with the non-death group (all P<0.05). ROC curve analysis revealed that the D_1, D_2, D_3 scores, and ΔD_1 significantly predicted mortality ( P<0.001), with areas under the curve (AUCs) of 0.786, 0.866, 0.901, and 0.843, respectively. The sensitivity values were 74.36%, 57.89%, 62.85%, and 86.84%, while specificity values were 70%, 100%, 100%, and 67.65%, respectively. In the HSCT group, the D_-1, D_1, D_2, D_ 3, scores and ΔD_1 were predictive of HCU mortality, with AUCs of 0.833, 0.794, 0.871, 0.846, and 0.795, respectively. Sensitivity values for these scores were 100%, 85.71%, 71.43%, 57.14%, and 57.14%, while specificity values were 73.33%, 70.59%, 91.33%, 100%, and 100%, respectively. In the leukemia group, the D_1, D_2, D_3 scores, and ΔD_1 were predictive of HCU mortality, with AUCs of 0.760, 0.829, 0.846, and 0.756, respectively. Sensitivity values were 71.43%, 78.57%, 53.85%, and 71.43%, while specificity values were 76.19%, 78.95%, 100%, and 63.16%, respectively. For all patients, the D_3 score exhibited the highest specificity, while the ΔD_1 demonstrated the highest sensitivity. For patients in both the HSCT and leukemia groups, the sensitivity and specificity values of the D_1 and D_3 scores exceeded those of the ΔD_1. Conclusion:For patients with hematologic critical illness, including leukemia and those undergoing HSCT hospitalized in the HCU, D_1, D_2, D_ 3 scores and ΔD_1 are significantly associated with HCU mortality.

Objective·To prepare self-assembled drug-loaded nanoprobes with activatable chemical exchange saturation transfer(CEST)imaging capability,and evaluate their imaging performance and therapeutic potential for photodynamic-sensitized pyroptosis in breast cancer in vivo and in vitro.Methods·GC nanoprobes co-loaded with gemcitabine(Gem)and chlorin e6(Ce6)were constructed by using a self-assembly strategy.The physicochemical properties of the GC nanoprobes were characterized by scanning electron microscopy(SEM)and dynamic light scattering(DLS).The pH-/time-dependent CEST activation and drug release profiles were investigated.The 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)probe was used to detect the generation of reactive oxygen species(ROS),and enzyme-linked immunosorbent assay(ELISA)was used to detect the release of inflammatory factors such as interleukin-1β(IL-1β)and IL-18 in mouse breast cancer 4T1 cells after treatment with GC nanoprobes with synergistic laser irradiation.Immunofluorescence was performed to detect immunogenic cell death(ICD)markers,including calreticulin(CRT)and high mobility group box 1 protein(HMGB1).The 4T1 breast cancer mouse models were established to validate tumor-specific CEST activation and evaluate anti-tumor efficacy by measuring tumor volume and detecting inflammatory factors and ICD markers.Results·SEM and DLS confirmed the uniform spherical morphology of the GC nanoprobes.The CEST imaging results showed that the nanoprobes had excellent pH-concentration and time-dependent activation imaging effects both in the simulated acidic microenvironment and at the cellular level in vitro.The drug release from this drug-loaded nanoprobe was 80％at pH 5.0,which was significantly higher than at pH 7.4(P=0.003).DCFH-DA fluorescence staining demonstrated that GC-mediated photodynamic therapy induced a significant generation of ROS.Analysis of pyroptosis-related factors revealed a marked increase in the release levels of IL-1β and IL-18(both P＜0.05),along with elevated fluorescence expression of CRT and HMGB1.The in vivo CEST imaging results showed that the CEST signal at the tumor site was significantly enhanced,peaking at 4 h with tail vein injection of GC.The GC nanoprobes with synergistic laser irradiation group showed markedly elevated inflammatory factors(IL-1β,IL-18),changed ICD biomarkers(HMGB1 and CRT),and significant tumor suppression,compared to the PBS control group(all P＜0.05).Conclusion·The GC nanoprobes enables specific CEST imaging-guided photodynamic therapy,effectively inducing pyroptosis and precise ablation of breast cancer.

The nucleophosmin 1(NPM1)muta-tion is one of the most frequent subtypes in acute myeloid leukemia(AML).Under the conditions of FLT3-internal tandem duplications(FLT3-ITD)and/or DNMT3A co-mutations or adverse cytogenetics,the originally favorable prognosis will deteriorate.In recent years,studies have found that multiple endocrine neoplasia protein(Menin)inhibitors tar-geting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX(homeotic gene)and MEIS1(myeloid ecotropic vi-ral integration site 1)in NPM1-mutated AML,dem-onstrating remarkable anti-leukemia activity.This article aims to review the mechanism and clinical research of Menin inhibitors,novel small molecule targeted drugs in NPM1-mutated AML,as well as the resistance mechanism of Menin inhibitors,hop-ing to provide promising approaches for the subse-quent treatment of NPM1-mutated AML patients.

Diseases caused by animal virus infection seriously restricts the healthy development of animal husbandry.In-depth study of the molecular mechanism of viral replication and pathogenesis will provide theoretical basis for screening vaccine and drug targets.N6-methyladenosine(m6 A)modification occurs extensively in viral and host transcriptomes and affects viral replication and pathogenicity by regulating gene expression,which acts as a novel regulator of gene expression in addition to DNA and protein modifications.Insight into the regulatory molecular mechanism of m6 A modification in virus infection is the research hotspots and frontiers.In recent years,there are re-ports of alternation of the m6 A modification-associated epitranscriptomes and related function a-nalysis during virus infection.Here,we summarize the alternation of the epitranscriptomes induced by African swine fever virus(ASFV),porcine reproductive and respiratory syndrome virus(PRRSV),porcine epidemic diarrhoea virus(PEDV),cestode virus(CSFV),porcine pseudorabies virus(PRV),Marek's disease virus(MDV),Newcastle disease virus(NDV),avian leukaemia virus(ALV)and duck hepatitis A virus(DHAV)infection,and the subsequent effects on viral replica-tion and pathogenicity.We also discuss the potential role and molecular mechanism of m6 A modification in animal virus replication and pathogenesis,which will contributes to the prevention and control for animal disease.

Purpose To explore the clinical and pathological characteristics of gastric amphicrine carcinoma(AC).Methods Clinical data of 12 patients with gastric AC were collected,and their clinical pathological character-istics and histological morphology were observed.Immunohistochemical staining,special staining,and electron micros-copy techniques were used to analyze their immune phenotype and ultrastructure.Molecular pathology was used to de-tect microsatellite status.Relevant literature was reviewed.Results Ten cases of gastric AC were located at the junc-tion of the esophagus and stomach/cardia,1 case at the gastric angle,and 1 case in the gastric antrum.The average maximum diameter of tumors was 4.25 cm.There were different proportions of tumor cells with signet-ring like charac-teristics in all cases.Four cases had neuroendocrine carcinoma components,and another 4 had adenocarcinoma.Elev-en cases had nerve invasion and vascular cancer thrombus.Eleven cases invaded the serosal layer/submucosal layer,and 1 case invaded the submucosal layer.Ten cases had lymph node metastasis.All 12 cases showed diffuse expression of CKpan and Syn,with 3 cases showed diffuse expression of CgA and 7 cases showed diffuse expression of CD56.The average proliferation index of Ki67 was 78.9％.Special staining showed clear intracellular mucus.Electron microscopy examination revealed electron dense particles and mucus particles within the tumor cells.A total of 10 patients were fol-lowed up,of which 7 survived,and 3 patients died from multiple systemic metastases at 0,24,and 30 months postop-eratively.Conclusion Gastric AC was more common in the junction of the esophagus and stomach/cardia,and histol-ogy shows a higher invasiveness.Their clear diagnosis depends on histological morphology,immunohistochemistry,and special staining.

Purpose To summarize the clinical pathological and immunohistochemical characteristics of esophage-al carcinoma with ductal differentiation of esophageal gland,and analyze the somatic mutation characteristics,key driv-ing mutation genes,and significantly mutated genes based on whole exome sequencing.Methods The clinicopatho-logical features of 9 cases of esophageal carcinoma with esophageal duct differentiation were retrospectively analyzed,and the immunohistochemistry EnVision two-step method was used to stain them,and 3 of the samples were subjected to whole exome sequencing and data analysis.Results Among the 9 patients,6 were males and 3 were females.The average age was 68.3 years old(61-80 years old).All 9 cases were located in the middle-lower segment of the e-sophagus.The diameter of the lesion was from 1.5 cm to 3.5 cm.Most areas of the tumor had a double-layer epithelial structure,including the inner layer of luminal epithelium and the outer layer of basal epithelium.Focal areas could be seen with keratinization and mucinous cells.Immunohistochemistry showed that CK7 was positive in the inner epitheli-um,while p63 was positive in the outer basal epithelium.S-100,SOX10 and c-myb were all negative,and p53 was mutated(diffuse strongly positive).The results of whole exome sequencing analysis showed somatic mutation character-istics(796 SNV,37 InDel,482 CNV),key driving mutation genes(12),and significantly mutated genes(TP53).No intraepithelial neoplasia was observed on the surface squamous epithelium of all cases,and no Barrett's esophagus or ectopic gastric mucosa was observed.The average follow-up time was 21.9 months(8 days-51 months),with 8 ca-ses surviving and 1 case dying of severe pulmonary infection 8 days after surgery.Conclusion Esophageal carcinoma with ductal differentiation of esophageal gland is a rare epithelial derived malignant tumor of the esophagus,character-ized by unique morphological,immunohistochemical,and molecular changes.