Objective: To analyze the epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province from 2019 to 2023, so as to provide the reference for strengthening SFTS prevention and control. Methods: Data on laboratory-confirmed SFTS cases in Zhejiang Province from 2019 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data, geographic environment and socioeconomic factors during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts, Geospatial Data Cloud, and Zhejiang Statistical Yearbook, respectively. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of SFTS from 2019 to 2023, and a Bayesian spatio-temporal model was constructed to analyze the influencing factors of SFTS incidence. Results: A total of 578 SFTS cases were reported in Zhejiang Province from 2019 to 2023, with an annual average incidence of 0.23/105. The peak period was from May to July, accounting for 52.60%. There were 309 males and 269 females, with a male-to-female ratio of 1.15∶1. The cases were mainly aged 50-<80 years, farmers, and in rural areas, accounting for 82.53%, 77.34%, and 75.43%, respectively. Taizhou City and Shaoxing City reported more SFTS cases, while Shaoxing City and Zhoushan City had higher annual average incidences of SFTS. The Bayesian spatio-temporal interaction model showed good goodness of fit. The results showed that mean temperature (RR=1.626, 95%CI: 1.111-2.378) and mean wind speed (RR=1.814, 95%CI: 1.321-2.492) were positively correlated with SFTS risk, while altitude (RR=0.432, 95%CI: 0.230-0.829) and population density (RR=0.443, 95%CI: 0.207-0.964) were negatively correlated with SFTS risk. Conclusions SFTS in Zhejiang Province peaks from May to July. Middle-aged and elderly people and farmers are high-risk populations. Taizhou City, Shaoxing City, and Zhoushan City are high-incidence areas. Mean temperature, mean wind speed, altitude, and population density can all affect the risk of SFTS incidence.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To study the epidemic characteristics and healthcare-seeking behavior of dengue fever cases in Zhejiang Province, and to provide a scientific basis for developing dengue fever prevention and control strategies.Methods:Data on dengue fever epidemic in Zhejiang Province from January to December 2024 were collected from the Information System for China Disease Control and Prevention and individual case reports. Descriptive epidemiological methods were used to analyze the distribution by the three dimensions (time, region, and population), healthcare-seeking behavior, importation sources, and laboratory test results of dengue fever cases in Zhejiang Province.Results:From January to December 2024, Zhejiang Province reported a total of 289 dengue fever cases (including 25 foreigners), with an incidence rate of 0.44/100 000, including one severe case and no death, and 13 were local, 108 were domestically imported, and 168 were internationally imported. The epidemic had affected 70 districts (counties, cities) across all 11 cities in the province. Cases were reported monthly, with the peak incidence concentrated from July to November. The age of dengue fever cases was 38 (30, 48) years old, ranging from 2 to 75 years old, with a higher incidence in the 30 - 39 age group (31.14%, 90/289). The male-to-female ratio was 1.86 ∶ 1.00 (188 ∶ 101). Occupational distribution was predominantly commercial service workers (28.03%, 81/289). The number of healthcare-seeking for local cases was 2 (1, 2) times, ranging from 1 to 6 times. The number of healthcare-seeking for imported cases was 1 (1, 2) times, ranging from 1 to 4 times. The interval between the onset and diagnosis of local cases was 3.5 (1.0, 5.0) days, ranging from 0 to 6 days. The interval between the onset and diagnosis of imported cases was 3(1, 4) days, ranging from 0 to 6 days. Domestically imported cases originated from Guangdong Province (102 cases), Yunnan Province (3 cases), Hunan Province (1 case), with 2 cases had unknown original provinces. Internationally imported cases mainly came from Indonesia (33 cases), Thailand (22 cases), Laos (18 cases). Serotyping of dengue virus was determined for 283 cases, with 157 cases of type Ⅰ, 88 cases of type Ⅱ, 34 cases of type Ⅲ, and 4 cases of type Ⅳ.Conclusions:The dengue fever cases in Zhejiang Province in 2024 is primarily international importation, the interval between the onset and diagnosis of local cases is relatively long. Prevention and control efforts should strengthen surveillance and early warning based on dengue fever's epidemic characteristics, and reinforcing port quarantine, mosquito vector control, and health education for high-risk populations.

Objective:To study the epidemic characteristics and healthcare-seeking behavior of dengue fever cases in Zhejiang Province, and to provide a scientific basis for developing dengue fever prevention and control strategies.Methods:Data on dengue fever epidemic in Zhejiang Province from January to December 2024 were collected from the Information System for China Disease Control and Prevention and individual case reports. Descriptive epidemiological methods were used to analyze the distribution by the three dimensions (time, region, and population), healthcare-seeking behavior, importation sources, and laboratory test results of dengue fever cases in Zhejiang Province.Results:From January to December 2024, Zhejiang Province reported a total of 289 dengue fever cases (including 25 foreigners), with an incidence rate of 0.44/100 000, including one severe case and no death, and 13 were local, 108 were domestically imported, and 168 were internationally imported. The epidemic had affected 70 districts (counties, cities) across all 11 cities in the province. Cases were reported monthly, with the peak incidence concentrated from July to November. The age of dengue fever cases was 38 (30, 48) years old, ranging from 2 to 75 years old, with a higher incidence in the 30 - 39 age group (31.14%, 90/289). The male-to-female ratio was 1.86 ∶ 1.00 (188 ∶ 101). Occupational distribution was predominantly commercial service workers (28.03%, 81/289). The number of healthcare-seeking for local cases was 2 (1, 2) times, ranging from 1 to 6 times. The number of healthcare-seeking for imported cases was 1 (1, 2) times, ranging from 1 to 4 times. The interval between the onset and diagnosis of local cases was 3.5 (1.0, 5.0) days, ranging from 0 to 6 days. The interval between the onset and diagnosis of imported cases was 3(1, 4) days, ranging from 0 to 6 days. Domestically imported cases originated from Guangdong Province (102 cases), Yunnan Province (3 cases), Hunan Province (1 case), with 2 cases had unknown original provinces. Internationally imported cases mainly came from Indonesia (33 cases), Thailand (22 cases), Laos (18 cases). Serotyping of dengue virus was determined for 283 cases, with 157 cases of type Ⅰ, 88 cases of type Ⅱ, 34 cases of type Ⅲ, and 4 cases of type Ⅳ.Conclusions:The dengue fever cases in Zhejiang Province in 2024 is primarily international importation, the interval between the onset and diagnosis of local cases is relatively long. Prevention and control efforts should strengthen surveillance and early warning based on dengue fever's epidemic characteristics, and reinforcing port quarantine, mosquito vector control, and health education for high-risk populations.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.

This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

Objective:The epidemiological and host animal pathogen data of leptospirosis in the population of Zhejiang Province in 2023 were analyzed, providing scientific basis for formulating prevention and control strategies of leptospirosis.Methods:The data of human leptospirosis in the population were collected from the China Information System for Disease Control and Prevention, and analyzed using descriptive epidemiological methods. The data on isolation, culture, and nucleic acid testing of Leptospira pathogens from mouse kidneys, frog kidneys, pig kidneys, and duck kidneys as well as duck serum antibody data were collected from Zhejiang Provincial Center for Disease Control and Prevention "Leptospirosis Surveillance Project of Zhejiang Province". The carrying and changing status of Leptospira epidemic microbiota in populations and host animals were analyzed. Results:In 2023, a total of 83 cases of leptospirosis were reported in Zhejiang Province, with a incidence rate of 0.126 2/ 100 000, aged (62.66 ± 11.31) years, including 68 males and 15 females. Leptospirosis cases were reported in 11 cities, mainly concentrated in the southern cities of Wenzhou City, Lishui City and Taizhou City(a total of 68 cases), accounting for 81.93% of the total number of cases. August to October were high incidence months for leptospirosis (a total of 70 cases), accounting for 84.34% of the total number cases. The male to female ratio of patients was 4.53 ∶ 1.00, and all were adults ≥20 years old, the middle and old people aged 45 - 79 years were the high-risk population (a total of 77 cases), accounting for 92.77% of the total number of cases. The patient's occupation was mainly farmers, with a total of 54 cases, accounting for 65.06% of the total number cases. The shortest time from onset to initial diagnosis for patients with leptospirosis was 0 day, and the longest was 13 days. The shortest time from initial diagnosis to confirmed diagnosis was 0 day, and the longest was 16 days. The 72.29% of the leptospirosis cases (60 cases) had a history of field labor or suspected contact with contaminated water within one month before the onset of the disease, and 18.07% of the leptospirosis cases (15 cases) had a history of contact with animals such as mice, frogs, pigs, cows, dogs, fish or ducks, or their excreta within one month before the onset of the disease. The average nucleic acid positive rate of host animals with leptospirosis was 5.92% (31/524) in mouse kidney, 6.74% (36/534) in frog kidney, and 0.66% (1/151) in pig kidney. The isolation and culture of leptospirosis from duck kidney, nucleic acid detection, and antibody detection in duck blood were all negative. The leptospirosis bacteria detected in human population were serogroup Icterohaemorrhagiae (3 samples) and Hebdomadis (4 samples), and the bacteria group detected in host animals was serogroup Icterohaemorrhagiae (3 samples). Conclusions:The outbreak of leptospirosis in Zhejiang Province mainly occurs in the summer and autumn, with the affected areas mainly concentrated in the southern region of Zhejiang Province. The affected population is mainly middle-aged and elderly males, and the population carrying Leptospira is still mainly composed of the serogroup Icterohaemorrhagiae and the Hebdomadis, with the host animal being the serogroup Icterohaemorrhagiae.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.