ObjectiveTo analyze the epidemiological characteristics and trends of hand-foot-mouth disease (HFMD) in Hangzhou, so as to provide an evidence for developing effective prevention and control measures and evaluating the control effects. MethodsThe incidence data of HFMD in Hangzhou were collected from the Infectious Disease Reporting Information Management System of China Information System for Disease Control and Prevention. Descriptive epidemiology was applied to analyze the temporal, spatial and demographic distribution characteristics and etiology monitoring results of HFMD cases in Hangzhou from 2010 to 2023. Joinpoint regression model was used to analyze the trends of incidence rate of HFMD. Furthermore, circular distribution method was utilized to calculate the incidence peak of HFMD. ResultsFrom 2010 to 2023, the average annual reported incidence rate of HFMD in Hangzhou was 138.85/100 000, the proportion of severe cases was 0.04%, the mortality rate was 0.01/100 000, and the case fatality rate was 5.30/100 000. Both the total incidence rate and the incidence rate by sex showed an increasing trend. The annual reported incidence rate in males (158.72/100 000) was higher than that in females (117.61/100 000). The reported incidence rate showed a significant seasonal characteristic, with summer being the peak of epidemic. The results of surveillance samples suggested that the prevalence of HFMD in Hangzhou is characterized by the co-existence of multiple pathogens, with EV-A71 and CV-A16 being the dominant pathogens in the previous years and CV-A6 being the dominant pathogen since 2018. The proportion of EV-A71 in severe cases (77.19%) was higher than that in ordinary cases (15.37%), in addition, its proportion in ordinary cases, severe cases, and fatal cases all showed a decreasing trend. ConclusionThe incidence rate of HFMD in Hangzhou is still high, so it’s still necessary to continue to strengthen the prevention and control measures for key populations. In recent years, CV-A6 has been the main prevalent pathogen in Hangzhou. Further efforts in pathogen detection and analysis should be enhanced in the future.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

OBJECTIVE: To analyze the changes in coagulation during the treatment of acute promyelocytic leukemia (APL) and explore the influencing factors of coagulation in patients with APL. METHODS: Data of 166 APL patients admitted to our hospital from November 2018 to May 2023 were retrospectively analyzed, and the changes of various clinical indicators before and during treatment were compared. 166 APL patients were divided into abnormal coagulation group (n =115) and normal coagulation group (n =51) according to whether they experienced coagulation dysfunction. The basic information, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was used to screen risk factors for coagulation dysfunction and established logistic regression model. Then we developed a neural network model and ranked the importance of the influencing factors, and used receiver operating characteristic (ROC) curves to evaluate the predictive performance of the two models. RESULTS: The comparative results of various clinical indicators in 166 APL patients before and during treatment showed that systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR), platelet (PLT) and fibrinogen (FIB) were significantly increased during the treatment (P < 0.05), while glycosylated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), serum creatinine (SCr), high-sensitivity C reactive protein (hs-CRP), IL-6, TNF-α, TGF-β, white blood cells (WBC), absolute neutrophil count (ANC), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), fibrinogen degradation products (FDP) and lactate dehydrogenase (LDH) were significantly decreased during the treatment (P < 0.05). The proportion of patients with hemorrhage and high-risk APL in the abnormal coagulation group was significantly higher than that in the normal coagulation group (P < 0.05). The levels of IL-6, TNF-α, WBC, ANC, D-D, FDP and LDH in the abnormal coagulation group were significantly higher than those in the normal coagulation group (P < 0.05). The influencing factors selected by univariate analysis were incorporated into logistic regression analysis and neural network model to predict the risk of coagulation dysfunction in APL patients. ROC curves showed that the AUC of the two models were 096 and 0.908, the sensitivity were 0.824 and 0.892, the specificity were 0.940 and 0.904, the Youden index were 064 and 0.796, and the accuracy were 0.882 and 0.898, respectively. CONCLUSION High risk stratification, hemorrhage, elevated WBC, LDH, ANC and FDP levels are independent risk factors for coagulation dysfunction in APL patients. The logistic regression model and neural network model based on these risk factors demonstrate good predictive performance for coagulation dysfunction in APL patients.
Humans ; Leukemia, Promyelocytic, Acute/therapy* ; Blood Coagulation ; Retrospective Studies ; Male ; Female ; Risk Factors ; Logistic Models ; Middle Aged ; Adult ; ROC Curve

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective: To establish anin vitromodel of ferroptosis induced by Erastin and RAS-selective lethal 3(RSL3) in hepatoma cells, and to provide theoretical basis for the development of novel therapeutic strategies for HCC. Methods: Hepatoma cells(HCCLM3, HepG2, Hep3B, Huh7 and PLC/PRF/5) in logarithmic growth phase were treated with Erastin(0-40 μmol/L) and RSL3(0-10 μmol/L) at double concentrations respectively. After 24 h, CCK-8 method was used to detect cell viability, draw growth curve, calculate IC50, and HCC cells sensitive to inducers were selected for follow-up experiments. The effect of inducer on the state of hepatoma cells was observed under light microscope, and immunoblotting and flow cytometry were used to verify whether the ferroptotic modelin vitrowas successfully constructed. Results: Huh7, Hep3B and HepG2 cells were sensitive to Erastin and RSL3, but HCCLM3 and PLC/PRF/5 were insensitive to Erastin and RSL3. When the concentration of Erastin and RSL3 reached the maximum, the survival rate was still above 65%. Huh7, Hep3B and HepG2 cells were selected for subsequent experiments. Compared with the control group, the expression of Glutathione peroxidase 4(GPX4), a ferroptotic marker, was down-regulated in a concentration-dependent manner. In Huh7, Hep3B and HepG2 cells, lipid reactive oxygen species(ROS) levels significantly increased after 24 h treatment with 10 μmol/L and 20 μmol/L Erastin, respectively; in Huh7 cells, lipid ROS levels significantly increased after 24 h treatment with 0.5 μmol/L and 1 μmol/L RSL3, respectively; in Hep3B and HepG2 cells, lipid ROS levels significantly increased after 24 h treatment with 1 μmol/L and 2 μmol/L RSL3, respectively, compared with control group. Conclusion Huh7, Hep3B and HepG2 cells are highly sensitive to Erastin and RSL3. Huh7, Hep3B and HepG2 cells treated with 10 μmol/L Erastin for 24 h are good models for simulating ferroptosis induced by Erastinin vitro, Huh7 cells treated with 0.5 μmol/L RSL3 for 24 h and Hep3B and HepG2 cells treated with 1 μmol/L RSL3 for 24 h are good models for simulating ferroptosis induced by RSL3in vitro.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To investigate the diagnostic value of the T2WI gray scale ratio for Hashimoto's thyroiditis(HT).Methods The T2WI-iterative decomposition of water and fat with echo asymmetry and least square estimation(IDEAL)quantitation sequence water images of 22 HT cases were analyzed retrospectively.The gray scale ratio of the thyroid,sternocleidomastoid muscle,trachea cavity,and subcutaneous fat at the same layer were measured on the picture archiving and communication systems(PACS).The gray scale ratios of thyroid/sternocleidomastoid muscle(T/M),thyroid/trachea cavity(T/Tr),and thyroid/lipid(T/L)were calculated.The intraclass correlation coefficient(ICC)was used to evaluate the consistency among the measurements,and the optimal threshold for distinguishing HT from non-HT was determined via the receiver operating characteristic(ROC)curve.The Spearman correlation analysis was used to analyze the correlation between T/M,T/Tr,T/L ratios,and titers of thyroid peroxidase antibody(TPO-Ab)and thyroglobulin antibody(Tg-Ab),respectively.Results On the T2WI-IDEAL quantitation sequence water images,the(x)±s of T/M,T/Tr,T/L ratios for HT and non-HT were 2.17±0.47 and 1.62±0.21(t=14.90,P<0.001),9.40±3.24 and 4.87±2.93(t=11.42,P<0.001),1.66±0.32 and 1.21±0.31(t=7.51,P<0.001),respectively.The area under the curve(AUC)of T/M,T/Tr,and T/L ratios for diagnosing HT were 0.89,0.86,and 0.85,respectively;the optimal thresholds were 1.90,3.50,and 1.36,and the sensitivity and specificity were 72.7%and 100%,100%and 40.5%,95.5%and 29.7%,respectively.The T/M ratio had a moderate correlation with TPO-Ab(r=0.513,P<0.05),and T/Tr,T/L ratios had a mild correlation with TPO-Ab,respectively.Conclusion The T/M ratio in the T2WI gray scale ratio can quantitatively and objectively distinguish HT from non-HT to some extent and is correlated with TPO-Ab.It has extremely high specificity and holds promise as a non-invasive imaging method for the diagnosis of incidental HT.

Objective To investigate the value of computer-assisted quantification of pulmonary embolism volume(PEV)in identifying mild-to-high-risk acute pulmonary embolism(APE).Methods We retrospectively enrolled 143 patients with suspected APE confirmed by computed tomography pulmonary angiography(CTPA)at Yan'an University Affiliated Hospital from January 2017 to December 2020.According to the 2018 Chinese Guidelines for Diagnosis,Treatment and Prevention of Pulmonary Thromboembolism,all the patients were divided into low-risk group(n=88)and mild-to-high-risk group(n=55).We collected the patients'basic demographic data,clinical manifestations,and serum levels of N-terminal-B type natriuretic peptide precursor(NT-proBNP)and D-dimer.Based on CTPA images,the degree of pulmonary thromboembolism was artificially evaluated to obtain the pulmonary artery occlusion index(PAOI).The thrombus was segmented using the pulmonary embolism detection tool based on digital lung,and PEV was calculated.We compared the differences in clinical and laboratory indicators and PAOI and PEV between the two risk groups.We analyzed the value of PAOI and PEV in identifying mild-to-high-risk APE using receiver operating characteristic(ROC)curves,and used Logistic regression analysis to identify independent risk factors in predicting mild-to-high-risk APE.Different models were established.Results Compared with the low-risk group,APE patients in the mild-to-high-risk group were older(P＜0.05),had lower diastolic blood pressure(P＜0.05),higher levels of D-dimer and NT-proBNP(P＜0.05),lower levels of platelet count,arterial oxygen partial pressure and arterial carbon dioxide partial pressure(P＜0.05),and higher levels of PAOI and PEV(P＜0.001).ROC curve analysis showed that the area under the curve for PEV in identifying mild-to-high-risk APE was 0.809(95％CI:0.734-0.884),while that for PAOI was 0.753(95％CI:0.667-0.839).Logistic regression analysis showed that PEV and NT-proBNP were independent risk factors for mild-to-high-risk APE(P＜0.05).Conclusion PEV and NT-proBNP are independent risk factors for mild-to-high-risk APE.

Echinococcosis is a common zoonotic disease in livestock; the type with the highest incidence is cystic echinococcosis (CE). In clinical management, patients with CE of the liver in which the cyst wall is calcified have been found to have better prognoses than those without calcification. In this study, we collected calcified and uncalcified cyst wall tissue from patients with hepatic CE and observed significant changes in the expression of 2336 messenger ribonucleic acids (mRNAs), 178 long noncoding RNAs (lncRNAs), 210 microRNAs (miRNAs), and 33 circular RNAs (circRNAs) using high-throughput sequencing (HTS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed RNAs (DERNAs: DEmRNAs, DElncRNAs, DEmiRNAs, and DEcircRNAs) were performed to explore these RNAs’ potential biological functions and signaling pathways. Ultimately, the results of hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining confirmed the correlation between calcification and apoptosis of the cyst wall. In summary, this study was an initial exploration of the molecular-biological mechanism underlying spontaneous calcification of the hydatid cyst wall, and it provides a theoretical basis for exploring new targets for drug treatment in CE.

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.