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 investigate the distribution characteristics and analyze the clinical significance of dermatophagoides pteronyssinus allergen components in children with allergic rhinitis and asthma in Shenzhen.Methods:This study was a cross-sectional study. The clinical data of children with allergic rhinitis and asthma induced by dust mites admitted to the allergy clinic of Shenzhen Children′s Hospital from 2021 to 2024 were collected and the serum sIgE levels of dermatophagoides pteronyssinus, dermatophagoides farinae (Der p, Der f) and dermatophagoides pteronyssinus components (Der p 1, Der p 2, Der p 10, Der p 23) were detected by magnetic bead chemiluminescence method. The correlation between dermatophagoides pteronyssinus allergen components and clinical data of children was analyzed. According to the diagnosis, the children were divided into allergic rhinitis (AR) group and AR with asthma (ARAS) group. According to the age, the children were divided into preschool age (5 years ≤age<7 years), school age (7 years ≤age<10 years) and adolescence (10 years ≤age≤15 years). The expression differences of dermatophagoides pteronyssinus components among AR group and ARAS group and different age groups were compared.Results:A total of 314 children with allergic rhinitis and asthma caused by dust mites were included in the study, of whom 112 were male and 202 were female. There were 188 cases of AR and 126 cases of ARAS, aged 5-15 years, with a median age of 7.54 years and an average age of (8.02±2.24) years. BMI was 13.89-31.76 kg/m 2,the median BMI was 15.87 kg/m2 and average BMI was (16.55±3.05) kg/m2. There was not statistically significant difference in gender, age, BMI, blood eosinophils, blood basophils, FeNO, FVC and FEV1 between the AR group and the ARAS group ( P>0.05). There was significant difference in FEV1/FVC and small airway function indexes MMEF, MEF75%, MEF50% and MEF25% between the AR group and the ARAS group ( P<0.05). In the 314 children, the dermatophagoides pteronyssinus allergen components sensitization rates were in the order of Der p 1 (97.1%), Der p 2 (89.8%), Der p 23 (55.1%), Der p 10 (8.6%), and the difference in the positive rate was statistically significant (χ 2=658.31, P<0.001). There was not significant difference in Der p 1, Der p 2 and Der p 10 among children of different ages ( P>0.05). There was significant difference in Der p 23 among children of different ages (χ 2=7.29, P=0.03). A correlation analysis showed that Der p, Der f, Der p 1 and Der p 2 had a high positive correlation ( P<0.001). Eosinophils are positively correlated with Der p, Der f, Der p 1, Der p 2, Der p 10 and Der p 23 ( P<0.001). FeNO is positively correlated with Der p, Der f, and Der p 23 ( P<0.05). Small airway function indicators MMEF, MEF50% and MEF25% are negatively correlated with Der p, Der f and Der p 1 ( P<0.05). The sIgE levels of Der p, Der f, Der p 1, Der p 2 and Der p 10 in the AR group were significantly lower than those in the ARAS group ( P<0.05). In the ARAS group, 120 cases (95.24%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 71 cases (56.35%) showed positive results for at least 3 dermatophagoides pteronyssinus components. In the AR group, 171 cases (90.96%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 94 cases (50.00%) showed positive results for at least 3 dermatophagoides pteronyssinus components. Conclusion:Der p 1, Der p 2 and Der p 23 may be the main dermatophagoides pteronyssinus allergen components that induce allergic rhinitis and asthma in Shenzhen City. The elevation of sIgE levels in the dermatophagoides pteronyssinus components can aggravate the severity of lower airway eosinophilic inflammation and airway obstruction. Attention should be paid to the detection of dermatophagoides pteronyssinus components in children with poor response to dust mite-allergen specific immunotherapy.

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 epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools. Methods: Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA). Results: A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range. Conclusions The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.

Objective:To investigate the distribution characteristics and analyze the clinical significance of dermatophagoides pteronyssinus allergen components in children with allergic rhinitis and asthma in Shenzhen.Methods:This study was a cross-sectional study. The clinical data of children with allergic rhinitis and asthma induced by dust mites admitted to the allergy clinic of Shenzhen Children′s Hospital from 2021 to 2024 were collected and the serum sIgE levels of dermatophagoides pteronyssinus, dermatophagoides farinae (Der p, Der f) and dermatophagoides pteronyssinus components (Der p 1, Der p 2, Der p 10, Der p 23) were detected by magnetic bead chemiluminescence method. The correlation between dermatophagoides pteronyssinus allergen components and clinical data of children was analyzed. According to the diagnosis, the children were divided into allergic rhinitis (AR) group and AR with asthma (ARAS) group. According to the age, the children were divided into preschool age (5 years ≤age<7 years), school age (7 years ≤age<10 years) and adolescence (10 years ≤age≤15 years). The expression differences of dermatophagoides pteronyssinus components among AR group and ARAS group and different age groups were compared.Results:A total of 314 children with allergic rhinitis and asthma caused by dust mites were included in the study, of whom 112 were male and 202 were female. There were 188 cases of AR and 126 cases of ARAS, aged 5-15 years, with a median age of 7.54 years and an average age of (8.02±2.24) years. BMI was 13.89-31.76 kg/m 2,the median BMI was 15.87 kg/m2 and average BMI was (16.55±3.05) kg/m2. There was not statistically significant difference in gender, age, BMI, blood eosinophils, blood basophils, FeNO, FVC and FEV1 between the AR group and the ARAS group ( P>0.05). There was significant difference in FEV1/FVC and small airway function indexes MMEF, MEF75%, MEF50% and MEF25% between the AR group and the ARAS group ( P<0.05). In the 314 children, the dermatophagoides pteronyssinus allergen components sensitization rates were in the order of Der p 1 (97.1%), Der p 2 (89.8%), Der p 23 (55.1%), Der p 10 (8.6%), and the difference in the positive rate was statistically significant (χ 2=658.31, P<0.001). There was not significant difference in Der p 1, Der p 2 and Der p 10 among children of different ages ( P>0.05). There was significant difference in Der p 23 among children of different ages (χ 2=7.29, P=0.03). A correlation analysis showed that Der p, Der f, Der p 1 and Der p 2 had a high positive correlation ( P<0.001). Eosinophils are positively correlated with Der p, Der f, Der p 1, Der p 2, Der p 10 and Der p 23 ( P<0.001). FeNO is positively correlated with Der p, Der f, and Der p 23 ( P<0.05). Small airway function indicators MMEF, MEF50% and MEF25% are negatively correlated with Der p, Der f and Der p 1 ( P<0.05). The sIgE levels of Der p, Der f, Der p 1, Der p 2 and Der p 10 in the AR group were significantly lower than those in the ARAS group ( P<0.05). In the ARAS group, 120 cases (95.24%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 71 cases (56.35%) showed positive results for at least 3 dermatophagoides pteronyssinus components. In the AR group, 171 cases (90.96%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 94 cases (50.00%) showed positive results for at least 3 dermatophagoides pteronyssinus components. Conclusion:Der p 1, Der p 2 and Der p 23 may be the main dermatophagoides pteronyssinus allergen components that induce allergic rhinitis and asthma in Shenzhen City. The elevation of sIgE levels in the dermatophagoides pteronyssinus components can aggravate the severity of lower airway eosinophilic inflammation and airway obstruction. Attention should be paid to the detection of dermatophagoides pteronyssinus components in children with poor response to dust mite-allergen specific immunotherapy.

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.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

PURPOSE: Tumor xenograft model is an indispensable animal cancer model. In esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft model establishes tumor xenograft in the animal esophagus, which allows the study of tumorigenesis in its native microenvironment. MATERIALS AND METHODS: In this study,we described two simple and reproducible methods to develop tumor xenograft at the cervical or the abdominal esophagus in nude mice by direct injection of ESCC cells in the esophageal wall. RESULTS: In comparing these two methods, the cervical one presented with more clinically relevant features, i.e., esophageal stricture, body weight loss and poor survival. In addition, the derived tumor xenografts accompanied a rapid growth rate and a high tendency to invade into the surrounding structures. This model was subsequently used to study the anti-tumor effect of curcumin, which is known for its potential therapeutic effects in various diseases including cancers, and its analogue SSC-5. SSC-5 was selected among the eight newly synthesized curcumin analogues based on its superior anti-tumor effect demonstrated in an MTT cell proliferation assay and its effects on apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor growth and invasion. CONCLUSION: Taken together, we have established a clinically relevant orthotopic tumor xenograft model that can serve as a preclinical tool for screening new anti-tumor compounds, e.g., SSC-5, in ESCC.
Animals ; Apoptosis ; Body Weight ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Cycle Checkpoints ; Cell Proliferation ; Curcumin* ; Epithelial Cells* ; Esophageal Stenosis ; Esophagus ; Heterografts* ; Mass Screening ; Mice ; Mice, Nude ; Therapeutic Uses

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ²=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ²=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Objective To develop a new botox-like polypeptide with anti-wrinkle and anti-aging functions, which will be used in the field of cosmetics and dermatology. Methods A series of new peptide compounds were synthesized via modifying the structure of SYN-AKE by peptide synthesis technology. Simulating muscle contraction by using co-culture model of human muscle cells and mouse embryonic spinal cord neurons to test the effects. Results Six new synthetic peptides were selected. The results showed that the muscle contraction frequency was lowered by adding C19 H30 N5 O4 compound than adding SYN-AKE in 1 min(P<0.05). Conclusion C19H30N5O4 is expected to become a new cosmetic peptide raw material and dermatology drug in the field of anti-wrinkle and anti-aging.