Diabetes mellitus is one of the common endocrine diseases in clinic, but its exact pathogenesis not yet been clarified. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3) inflammasome can not only be activated by upstream signaling pathways, which plays an important role in pyroptosis, apoptosis, necrosis, autophagy, etc., but also regulate downstream inflammatory factors to participate in the chronic inflammatory process of diseases. This article elucidates the role of NLRP3 inflammasome in the pathogenesis or intervention of diabetes and its complications, and provides a new direction for research. NLRP3 inflammasome and its regulated cytokines or receptors may be a new diagnostic or therapeutic targets for diabetes and its complications.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

Objective:To systematically evaluate the intelligence-assisted endoscopic diagnosis system based on deep learning (DL-IEDS) for early cancer of the upper digestive tract.Methods:Literature on the value of DL-IEDS for diagnosis of early cancer of the upper digestive tract was searched in English (PubMed, Embase, Web of Science and Cochrane Library)and Chinese databases (Sinomed, CNKI, Wanfang and VIP). The quality of literatures was evaluated according to Quality Assessment of Diagnostic Accuracy Studies-2. The Rev Man 5.3, Meta-Disc 1.4 and Stata 15.1 were used for the meta-analysis.Results:Eight studies were included with a total of 9 675 images (including 2 748 images of early cancer). Meta-analysis results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and comprehensive diagnostic ratio of DL-IEDS in the diagnosis of early cancer of the upper digestive tract were 0.920, 0.874, 6.824, 0.103 and 71.109, respectively. The area under the curve (AUC) of summary receiver operating characteristics was 0.958 7. Five studies reported the results of DL-IEDS in the diagnosis of early gastric cancer, and the combined analysis showed that the pooled sensitivity and specificity were 0.840 and 0.845 respectively, and the AUC was 0.919. Four studies reported the accuracy rate of endoscopic experts and endoscopic novices in diagnosing early upper gastrointestinal cancer, and results showed that the pooled sensitivity, specificity and AUC were 0.693, 0.892 and 0.892 3, and 0.586, 0.860 and 0.754 5, respectively. Compared with endoscopy experts, the AUC of DL-IEDS in diagnosis of early upper gastrointestinal cancer showed no statistically significant difference ( Z=1.510, P=0.131), while compared with endoscopy novices, the difference was statistically significant ( Z=6.841, P<0.001). Conclusion:The DL-IEDS has high diagnostic accuracy for early upper digestive tract cancer, and can significantly improve the diagnostic ability of endoscopy novices.

Objective:To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation.Methods:The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed.Results:Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different ( P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant ( P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant ( χ2= 4.694, P = 0.030; χ2= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR 1 state, and 2 patients with recurrence after transplantation obtained CR 2 after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion:Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

Objective: To investigate herpesvirus infection in early stage of hematopoietic stem cell transplantation (HSCT) by multiplex polymerase chain reaction (PCR), and to explore the association between multiple herpesviruses infection and clinical characteristics in HSCT patients and its impact on post-transplant complications and prognosis. Methods: A total of 734 peripheral blood samples were collected from 90 patients undergoing HSCT in the Department of Hematology, the First Affiliated Hospital of Soochow University between February 2017 and August 2017. The peripheral blood specimens were obtained before and within 90 days after transplantation at different time points. Lab-Aid824 Nucleic Acid Extraction Mini Reagent was used to extract DNA and multiplex PCR assay was used to simultaneously detect 8 kinds of human herpesviruses from genomic DNA. The incidence of various herpesvirus infections, its correlation with clinical features and effects on post-transplant complications and prognosis were analyzed. Results: The median follow-up time was 192 (range: 35-308) days. Among the 90 patients before transplantation, the incidence of herpes virus infection was 35.6% (32/90), including 12.2% (11/90) with one herpes virus infection and 23.3% (21/90) with multiple viruses infection. The incidence of herpes virus infection after transplantation was 77.8% (70/90), including 20.0% (18/90) with one herpes virus infection and 57.8% (52/90) with multiple herpes virus infection. Among the 52 patients with multiple herpes viruses infection, 30 (57.7%) patients were infected by 2 kinds of viruses, 18 (34.6%) patients by 3 kinds of viruses and 4 (7.7%) patients by 4 kinds of viruses. There was a correlation between HHV-6 and HHV-7 herpesvirus infection (OR=13.880, Q=0.026). EBV infection was related to HHV-7 infection (OR=0.093, Q=0.044). The age of patients was correlated with the incidence of HHV-1 infection before transplantation. There were 24 patients in our study experienced clinical symptoms associated with viral infection. The main manifestations were hemorrhagic cystitis (HC), interstitial pneumonia, enteritis, viral encephalitis and fever of unknown origin. EBV infection was related to HLA incompatibility and the inconsistent of the ABO blood group and grade Ⅱ-Ⅳ aGVHD after transplantation. HLA incompatibility and the unrelated donor and grade Ⅱ-Ⅳ aGVHD were related to multiple viruses infection. Conclusion Multiple herpesviruses were common in patients undergoing HSCT, which were closely related to HLA mismatch, unrelated donor and grade Ⅱ-Ⅳ aGVHD.

Objective To explore the clinical features of cytomegalovirus (CMV) and EpsteinBarr virus (EBV) infection after second hematopoietic stem cell transplantation (HSCT).Methods Twenty-five patients after second HSCT from Sep.2009 to Oct.2016 were collected,and CMV and EBV DNA in peripheral blood was detected regularly by polymerase chain reaction (PCR).Factors associated were compared by univariate analysis.Results The total incidence of CMV infection was 52.0％ (13/25) after second HSCT.The incidence of CMV infection was 100％ (2/2),33.3％ (5/15) and 75％ (6/8) in bone marrow group,peripheral blood stem cell group,and mixed group,respectively.Stem cell sources were significantly correlated with CMV infection (P =0.038),however,there was no significant difference in CMV infection rate among three groups (P＞0.05).None of preconditioning regimen,GVHD prophylaxis programs or severity of aGVHD were correlated with CMV infection after second HSCT (P＞0.05).The total incidence of EBV infection was 24.0％ (6/25) after second HSCT.The incidence of EBV infection was 100％ (2/2),6.7％ (1/15) and 37.5％ (3/8) in bone marrow group,peripheral blood stem cell group,and mixed group,respectively.Stem cell sources were significantly correlated with EBV infection (P =0.008).The EBV infection rate in bone marrow group was significantly higher than that in peripheral blood group (P =0.022),however,no significant differences were found between bone marrow group and mixed group,as well as between peripheral blood group and mixed group (P＞0.05).Transplant methods were significantly correlated with EBV infection (P =0.007).The EBV infection rate in haploidentical HSCT group (71.4％) was significantly higher than that in HLA-matched sibling HSCT group (0％) and autologous HSCT group (0％) (P =0.021 and 0.028),however,no significant differences were found between any other two groups (P＞0.05).None of preconditioning regimen,GVHD prophylaxis programs or severity of aGVHD were correlated with EBV infection after second HSCT (P＞0.05).Conclusion The incidence of CMV and EBV infection in patients undergoing second HSCT is high.Stem cell sources and transplant methods are associated with CMV and EBV infection after second HSCT.

[Objective] To explore the characteristics of the plantar pressure data of the patients with adolescent idiopathic scoliosis (AIS).[Methods] 56 AIS patients who were diagnosed from October 2015 to March 2017 in the East branch of the First Affiliated Hospital of Sun Yat-sen University divided into 3 groups,18 cases in spinal lateral bending to right,18 cases in spinal lateral bending to left,20 cases in type S who were thoracolumbar scoliosis.Another 19 healthy persons were as the control group.The left and right foot pressure,half foot pressure and other biomechanical data were compared.The changes of the plantar pressure and the Cobb angle were analyzed with the patients who wore orthopedic insoles.[Results] Compared with the control group,the mean pressure of the left foot and the pressure of the left anterior half of the right bending group were less than those of the control group,and the right half foot pressure were greater than those of the control group (P ＜ 0.017).To the left bending group,the mean pressure of right anterior half foot were less than those of the control group,and the right rear half foot pressure was greater than that of the control group (P ＜ 0.017).The pressure of the left anterior half foot of the S type scoliosis group was less than that of the control group.To the right bending group,the left foot average pressure (44.7％±6.0％) was significantly less than the average pressure of right foot (55.4％ ± 6.0％).There was no difference in bilateral plantar pressure of the left bending group,S type group and control group.There was difference with the plantar pressure distribution in patients with only one curve after they wore orthotic insoles,but there was no difference in patients with type S.There was no significant difference in the Cobb angle after the patients wearing the orthotic insoles (P =0.102).[Conclusions] The right and left foot pressure symmetry of the right bending patients is poor,but the left and right plantar pressure in the patients with type S is symmetrical.The orthotic insole can be used to adjust the plantar pressure distribution in patients with a single curved scoliosis (left or right),but their effect on the patient's spinal lateral curvature should be further observed.

OBJECTIVETo evaluate the association between chemical exposure, DNA methylation status and gene-environment interactions in the development of childhood acute leukemia (AL).

METHODSFrom January 1st 2009 to December 31st 2010, an exploratory case-control study was conducted on childhood AL among children who were less than 15 years of age in Shanghai, China. A total of 131 patients with newly diagnosed AL were recruited from 3 Shanghai children hospitals. The controls selected from the same hospital were healthy children who attended the physical check-up held by the department of Children's Healthcare, or who visited the clinic of developmental pediatrics or orthopedics (excluding blood diseases and malignant tumors). 140 controls matched with cases in gender and age were included in this study. Chemical exposure were investigated by questionnaires, methylation specific polymerase chain reaction (MSP) was adopted to analyze the methylation or deletion status of 8 genes, and gene-environment interactions were analyzed by relative excess risk of interaction (RERI), attributable proportion of interaction (API) and synergy index (S).

RESULTSThere were 131 and 140 subjects in case and control group, who were aged (6.9 ± 3.8) and (6.9 ± 3.9) years old (t = 0.01, P = 0.911), respectively. After adjusting age and other potential confounding factors, chemical substances' exposure of children/mother/father were all significantly higher in cases than that in controls (Children: OR = 3.90, 95% CI: 1.69-9.02; Mother: OR = 2.71, 95% CI: 1.12-6.52; Father: OR = 1.91, 95% CI: 1.05-3.47). For the 8 genes analyzed, the methylation status of DAPK and PTEN and P73 in case group were significantly higher than that in control group (cases: 3.1% (4 cases), 16.0% (21 cases), 7.6% (10 cases); controls: 0.7% (1 case), 2.9% (4 cases), 0.7% (1 case); χ²: 7.11, 16.90, 11.38; P value: 0.029, 0.000, 0.003). The methylation status of P16 in case group was significantly lower than that in control group (cases: 3.8% (5 cases); controls: 8.6% (12 cases), χ² = 10.33, P = 0.007). The interactions of children chemical substances' exposure and 3 genes' (PTEN, P16 and P73) methylation status were probably existed after adjusted for confounding factors (PTEN: RERI = -7.01, API = -2.14, S = 0.24; P16: RERI = 4.08, API = 0.53, S = 2.59; P73: RERI = 4.32, API = 0.48, S = 2.19), we also found the potential interaction between maternal chemical substances' exposure and PTEN, P16 gene methylation status (PTEN: RERI = -1.30, API = -0.38, S = 0.65; P16: RERI = 1.70, API = 0.38, S = 1.97).

CONCLUSIONThe study suggested the strong combined effects of chemical substances exposure of children and abnormal methylation status were risk factors of childhood AL, and there existed different interaction between them, which may indicate the important role in the pathogenesis process of childhood AL.

Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; China ; DNA Methylation ; Environmental Exposure ; Female ; Gene-Environment Interaction ; Humans ; Leukemia ; epidemiology ; Maternal Exposure ; Polymerase Chain Reaction ; Risk Factors

OBJECTIVETo investigate the association between children's and their parents' lifestyles, household environmental exposures and risk of childhood acute leukemia (AL).

METHODSA 1:2 matched case-control study of childhood AL was conducted in Shanghai between April 2011 and January 2014. The study enrolled 66 cases aged < 15, diagnosed with AL and 132 controls matched by age, gender and residence. All of the controls had no hematological diseases or previous history of malignancy. Children who had been adopted and had congenital genetic syndromes such as Down's syndrome or a positive HIV test result were not eligible as either cases or controls. Information was obtained from standardized face-to-face interviews of their parents/guardians with detailed questions on demographic characteristics, lifestyle, and household environment. Conditional logistic regression models were used to analyze effecting factors of childhood AL, odds ratios (OR) and their 95% confidence intervals (CI) were calculated.

RESULTSAmong 198 cases, 66 cases were aged (5.0 ± 3.7) years old, and 132 controls were aged (6.0 ± 3.8) years old (t = 0.48, P = 0.523). The paternal drink frequencies of cases and controls were 57.6% (38/66), and 31.1% (41/132), respectively (χ² = 4.91, P = 0.027). And the frequencies of household insecticides usage in the last year in the two groups were 78.8% (52/66), and 65.2% (86/132) (χ² = 3.87, P = 0.049). Chemical exposure during childhood (OR = 4.76, 95% CI: 1.34-16.89), maternal exposure to chemicals (OR = 4.51, 95% CI: 1.65-12.33), household insecticides use during 0-3 years of child (OR = 2.90, 95% CI: 1.31-6.39), and renovating after their children's birth (OR = 3.12, 95% CI: 1.26-7.74) were associated with an increased risk of childhood AL and these differences between the cases and the controls have statistical significance. Besides, we found that frequent contaction with other children during 0-3 years old (OR = 0.32, 95% CI: 0.15-0.69) and ventilation during sleeping in summer (OR = 0.43, 95% CI: 0.18-0.98) were associated with a decreased risk of childhood AL.

CONCLUSIONOur results support the association between children's and their parents' lifestyles, household environmental exposures and childhood AL.

Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; China ; Environmental Exposure ; Female ; Humans ; Insecticides ; Leukemia ; epidemiology ; Life Style ; Logistic Models ; Maternal Exposure ; Neoplasms ; Odds Ratio ; Parents ; Risk Factors