OBJECTIVE To investigate the potential mechanism by which Juanxiao decoction improves bronchial asthma （hereinafter referred to as “asthma”） based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome signaling pathway. METHODS Female SD rats were randomly assigned to normal group， model group and Juanxiao decoction low-， medium- and high-dose groups （0.36， 0.72 and 1.44 g/kg， calculated based on crude drug weight）， as well as positive control group （Dexamethasone acetate tablets， 0.2 mg/kg）， with 10 rats in each group. Except for the normal group， asthma models were established in the remaining groups via intraperitoneal injection of ovalbumin combined with aluminum hydroxide， followed by nebulized inhalation of ovalbumin. On day 14 of the experiment， rats in each group received intragastric administration of the corresponding solution or normal saline， once a day， for 7 consecutive days. Following the final administration， the following parameters were measured in each group： lung function indexes （forced vital capacity， forced expiratory volume in 0.3 second， peak expiratory flow）， serum levels of inflammatory markers （interleukin-1β， interleukin- 18）， and the percentages of inflammatory cells （lymphocytes， eosinophils， neutrophils） in bronchoalveolar lavage fluid. Histopathological changes in lung tissue were observed， and the protein and mRNA expressions of nuclear factor-kappa B （NF- κB）， NLRP3 and caspase-1 in lung tissue were detected. RESULTS Compared with the normal group， pathological changes such as alveolar wall thickening and inflammatory cell infiltration were observed in rats in the model group. All pulmonary function indicators were significantly reduced in rats in the model group and the administration groups. The levels of inflammatory markers， the percentages of inflammatory cells， and the protein and mRNA expressions of NF-κB， NLRP3 and caspase-1 were significantly elevated or up-regulated （P＜0.05）. Compared with the model group， pathological changes in rats in each dosage group of Juanxiao decoction were significantly alleviated， and all quantitative indicators showed dose-dependent improvements （P＜0.05）. CONCLUSIONS Juanxiao decoction can reduce airway inflammatory responses in asthmatic rats， alleviate lung function impairment， and improve pathological changes such as inflammatory cell infiltration. Those effects may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.

Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.

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.

Objective:To investigate the interaction of platelet factor 4(PF4)with tumor necrosis factor-α(TNF-α)in the pathoge-nesis of chronic periodontitis(Ⅲ-C).Methods:22 patients with chronic periodontitis(Ⅲ-C)and 22 subjects with periodontal health were recruited.Before and after periodontal treatment,the concentration of PF4 and TNF-α in gingival crevicular fluid(GCF)and ser-um,the amount of PF4 released by platelets after lipopolysaccharide(LPS)stimulated peripheral blood platelets were measured by ELISA.Flow cytometry was used to calculate the number of platelets in GCF before and after treatment.Results:The concentrations of PF4 and TNF-α in the GCF and serum of the patients were higher than those in the periodontal healthy group(P＜0.05).After treat-ment,the concentrations of PF4 and TNF-α in the GCF were significantly lower than those before treatment(P＜0.05),and the con-centrations of PF4 and TNF-α in the serum were unchanged(P＞0.05).After LPS stimulation of the platelets in blood before and after treatment,the concentration of PF4 released by the platelets was much higher in the patients than that in the healthy controls(P＜0.01),and the concentration was significantly lower after periodontal treatment than before treatment(P＜0.01).The number of CD41/CD61 double positive platelets and CD45 negative cells in GCF before periodontal treatment were 85 times and 87 times higher than those in periodontal healthy subjects,respectively(P＜0.01).Conclusion:PF4 and TNF-α have synergistic effect in the patho-genesis of chronic periodontitis.

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.

Objective To explore the comparison of the predictive value of three risk assessment tools on the chemotherapy-induced nausea and vomiting(CINV)in cancer patients.Methods From January 2022 to December 2022,convenience sampling was used to select 626 cancer patients with Intravenous chemotherapy in the Department of Hepatobiliary Pancreatic Oncology of Zhejiang Cancer Hospital as the research object.CINV risk assessment of patients was performed using George teams acute CINV prediction tool,Dranitsari's CINV risk assessment and CINV nomogram model.Area under curve(AUC),sensitivity,specificity and Youden index were used to compare the predictive value of the three tools.Results Totally 622 patients were ultimately included in the study,with an overall effective rate of 99.36%.There were 51.13%(318/622)patients who experienced CINV.Specifically,patients with grade 2 or higher acute CINV accounted for 18.17%(113/622).When using the three tools for acute CINV risk assessment,the AUC was respectively 0.591,0.616 and 0.558.And Dranitsari's CINV risk assessment has the highest sensitivity,acute and delayed chemotherapy-induced nausea and vomiting prediction tool has the highest specificity.Comparatively,Dranitsari's CINV risk assessment on the Yorden index is better.Conclusion The incidence of CINV in cancer patients is at a high level.The three tools can not effectively predict the risk of acute CINV.We need to develop a localized,multi-disease,standardized CINV risk assessment model for hospital.

Objective:To calculate the relative biological effectiveness (RBE) value of the released low-energy electrons in gadolinium neutron capture therapy ( 157GdNCT) based on microdosimetry. Methods:The Monte Carlo (MC) code Geant4-DNA package was used to simulate the energy deposition distribution and microdosimetry parameters of low-energy electrons released during gadolinium neutron capture treatment in different sensitive target volumes and physical models on track structures. On this basis, RBE value was obtained based on the microdosimetry kinetic model (MKM).Results:The low-energy electron RBE value was highly variable in different sensitive target volumes and decreases with increasing sensitive target volumes. With 6-nm-diameter sensitive target as reference, RBE value was 1.77 for 6-nm diameter, 1.53 for 10 nm diameter with percentage difference 13%, and 1.40 for 15-nm diameter with percentage difference of 21%, respectively. The effect of different Geant4-DNA physical models on the RBE of low-energy electrons was small. Using the RBE value of 1.53 for physical model option2 as reference, the RBE values of option6 and option7 were 1.49 and 1.52, respectively, with the percentage differences of 2.6% and 0.6%, respectively.Conclusions:The RBE values of low energy electrons released by 157GdNCT in different sensitive target volumes and physical models were calculated by MKM to be 1.40-1.77.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

Objective:To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases.Methods:From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) .Results:① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups ( P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups ( P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively ( P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % ( P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion:The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.