An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Successful Immune Reconstitution in a Patient with a TYK2 Deficiency after Allogeneic Stem Cell Transplantation from Unrelated Donors.

A boy with primary immunodeficiency, caused by a tyrosine kinase 2 (TYK2) mutation, presented with immune defects and a lifelong history of severe infections. Our aim was to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) could restore the patient's immune defenses and reduce susceptibility to infection. In the absence of a suitable HLA-matched blood relative to act as a donor, the patient received an allogeneic HSCT from unrelated donors. The patient's clinical data were analyzed in the Children's Hospital of Chongqing Medical University (Chongqing, China) before transplantation and during the 4-year follow-up period using a combination of western blotting (e.g., TYK2 and STAT levels), qRT-PCR (e.g., T cell receptor rearrangement excision circles, kappa deletion element recombination circles, and TYK2 transcript levels), and flow cytometry (e.g., lymphocyte subpopulations and CD107α secretion). We found that HSCT significantly reduced the incidence of severe infections, restored normal TKY2 levels, and reversed defects such as impaired JAK/STAT signaling in response to interferon-α or interleukin-10 treatment. Although the patient did not develop acute graft-versus-host disease (GVHD) after transplantation, he did experience chronic GVHD symptoms in a number of organs, which were effectively managed. Our findings suggest that HSCT is a feasible strategy for reconstituting the immune system in TYK2-deficient patients; however, the factors associated with GVHD and autoimmune thyroiditis development in TYK2-deficient patients undergoing HSCT warrant further investigation.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

Patients' perception of lifestyle advice as a mechanism between health shocks and health behaviours: Evidence from a longitudinal study in China.

Background: The heavy burden of non-communicable chronic diseases (NCDs) and the deficiency of health behaviours (HB) are threatening the middle- and older-aged population in China. However, little is known about the relational mechanism between health shocks (HS) and HBs, while the importance of patients' perception of lifestyle advice (PPLA) to initiate HB is insufficiently emphasised. In this study, we aimed to examine this perception as a mediator between HS and HB and the variety of mediation effects caused by the different contents of lifestyle advice. Methods: We retrieved panel data from the two latest waves of a nationally representative cohort, the China Health and Retirement Longitudinal Study (CHARLS). After constructing well-balanced groups through propensity score matching, we conducted descriptive and multilevel logistic regression analyses to analyse the state of and factors influencing PPLA. We employed the Preacher's Sobel test with 1000 replications bootstrap to examine the mediating effect of PPLA. Results: On a sample of 7922 respondents (post-propensity score matching), we found that HSs had a positive direct effect on HB, with observed decreases in smoking and drinking and increases in exercise. A limited and selected perception of lifestyle advice showed a gap between the advice given by providers and perceived by patients, with gender, education level, social support inside the family, self-reported health, comorbidity, treatment regimens, and utilisation of family doctors being significant influencing factors. Nevertheless, any content of lifestyle advice partially mediated the relationship in which HS increases non-addictive HB (exercise), while only the targeted and detailed content of lifestyle advice about corresponding behaviours partially mediated the effect between HS and addictive HB (smoking and drinking). Conclusions: This study provides the first evidence that PPLA partially mediates the positive effect of HS on HB. Personalised chronic disease management; targeted advice and interventions; and multiple social resources COULD BE beneficial for patients with HS to initiate HB.

Risk perception and trust in the relationship between knowledge and HPV vaccine hesitancy among female university students in China: a cross-sectional study.

BACKGROUND: Cervical cancer poses a heavy health burden in China, with the second highest incidence and mortality rate among female tumors, yet human papillomavirus (HPV) vaccination rate among female university students remain remains low. This study conducted a cross-sectional survey to assess the degree of HPV vaccine hesitancy among female university students and to explore the potential association between knowledge, risk perception, trust, and HPV vaccine hesitancy. METHODS: A total of 1,438 female university students from four Chinese cities were recruited through stratified, multistage, cluster sampling method. The mediation model was constructed using the Bootstrap method, introducing trust and risk perception as mediating variables to examine the effect of knowledge on HPV vaccine hesitancy. RESULTS: The study found that 8.9% (95%CI:7.4%∼10.4%) of the female university students exhibited HPV vaccine hesitancy. Pearson's correlation analysis revealed a negative association between vaccine hesitancy and knowledge, risk perception, and trust. The mediation model showed that knowledge had significant indirect effects on HPV vaccine hesitancy through trust (indirect effect: -0.224, 95% CI: -0.293 ∼ -0.167) and risk perception (indirect effect: -0.013, 95% CI: -0.033 ∼ -0.002). CONCLUSION: HPV vaccine hesitancy among female university students has mitigated, but still needs to be addressed. In addition, trust and risk perception are mediators mediating the relationship between knowledge with HPV vaccine hesitancy. Therefore, there is a need to strengthen public health education to improve knowledge, with a particular focus on providing information about trust and risk perception to reduce HPV vaccine hesitancy.

Factors associated with HPV vaccine hesitancy among college students: A cross-sectional survey based on 3Cs and structural equation model in China.

Despite the high effectiveness of HPV vaccines in preventing infection, vaccine hesitancy remains a concern, particularly in China. This study aimed to explore college students' attitudes toward HPV vaccination and identify associated factors. Data was collected through a cross-sectional survey using self-administered questionnaires in four cities from May to June 2022. Chi-square tests and logistic regression analyses were conducted to identify factors. Additionally, an integrated structural equation model (SEM) based on the 3Cs (confidence, convenience, complacency) was developed to understand underlying factors contributing to hesitancy. The results from 2261 valid questionnaires were enlightening. A significant 89.47% (59.4% for females) considered HPV vaccination necessary, with 9.82% remaining neutral and only 0.71% deeming it unnecessary. Factors like higher education, being a medical student, residing in urban areas, having medical insurance, more extraordinary living expenses, a family history of tumors, and a solid understanding of HPV played a role in perceiving the vaccine as necessary. Among the 1438 female respondents, 84.36% had no hesitancy toward HPV vaccination, 13.53% expressed hesitancy, and 2.11% refused vaccination. Factors like age, understanding of HPV, medical staff recommendations, living expenses, and family history influenced hesitancy levels. SEM revealed that the 3Cs significantly affected vaccine hesitancy. Factors like price, booking process, vaccination times, trust in vaccines, medical staff recommendations, efficiency, and risk perception collectively influenced hesitancy. In conclusion, this study found high acceptance of HPV vaccination but acknowledged the complexity of hesitancy factors. It recommends medical staff disseminate scientific knowledge, offer recommendations, simplify booking procedures, and expand vaccination sites to address vaccine hesitancy effectively.

The distribution of intestinal flora after hematopoietic stem cell transplantation in children.

BACKGROUND: This prospective study aimed to comprehensively understand the changes in intestinal flora at different stages after hematopoietic stem cell transplantation (HSCT) in pediatric patients and to analyze the effect of intestinal flora on acute graft versus host disease (aGVHD), especially on gastrointestinal graft versus host disease (GI GVHD). METHODS: A total of 32 children with primary diseases of primary immunodeficiency disease (PID) and thalassemia were included. 16S sequencing was used to characterize the microbiota layout at three time points peri-transplant including pre-transplant, Day +3, and Day +30. RESULTS: By comparing the intestinal flora of children with GI GVHD and those without GI GVHD, it suggests that in children with GI GVHD, the distribution of intestinal flora after transplantation was more variable and more chaotic (chao1 index, Friedman test, p = .029). Besides, Veillonella and Ruminococcaceae were more abundant before transplantation, Bifidobacteriaceae and Bacillales were more abundant after transplantation. Comparing children with PID and thalassemia, it was found that the destruction of gut microbiota diversity was more significant in children with thalassemia after transplantation. The comparison of children with 0-I° aGVHD and II-III° aGVHD indicates that children with II-III° aGVHD had more Bilophila before transplantation than children with 0-I° aGVHD. Additionally, exploratory analyses to evaluate correlations between clinical characteristics (medications, immune cell recovery, etc.) and microbiome features were also performed. CONCLUSIONS: This study has synthetically shown the distribution of intestinal flora after allo-HSCT, and some characteristic bacteria at different stages that may serve as potential biomarkers were screened out additionally, perhaps providing clues for the prevention and treatment of the disease.

Retrospective study of risk factors for pericardial effusion after haematopoietic stem cell transplantation in children.

OBJECTIVES: The clinical characteristics, risk factors and survival prognosis of pericardial effusion (PE) after haematopoietic stem cell transplantation (HSCT) in children were investigated. METHODS: Clinical data of children who underwent HSCT at the Children's Hospital Affiliated with Chongqing Medical University from January 2016 to December 2022 were analysed retrospectively. Cox proportional hazards regression and the Kaplan-Meier method were used to analyse the risk factors for post-HSCT PE and its impact on outcomes, respectively. RESULTS: We enrolled 452 patients with HSCT: 307 males and 145 females, with a median age of 3.4 (1.8 to 6.5) years at transplantation. Forty-five patients (10%) had PE within a median time of 25 (10.5 to 44) days, 42 (93%) within 100 days. Three patients with large PE were treated with pericardiocentesis and drainage, while the others were treated conservatively. Of the 45 patients with PE, 24 survived, and their PE disappeared after treatment. Graft-versus-host disease (GVHD) grade, abnormal pre-HSCT electrocardiogram, hepatic veno-occlusive disease (HVOD), pulmonary infection and Epstein-Barr virus (EBV) infection were risk factors for PE. The overall survival (OS) rates at 1, 3, and 5 years were 86.0%, 84.2%, and 82.3%, respectively. PE had a significant negative effect on OS after HSCT (P < 0.0001). Particularly, one patient with large PE died of pericardial tamponade. CONCLUSIONS: Post-HSCT PE usually occurred within 100 days. GVHD grade, abnormal pre-HSCT electrocardiogram, HVOD, pulmonary infection and EBV infection were closely related to PE. PE had a significant negative effect on OS rate.

Repurposing of rilpivirine for preventing platelet ß3 integrin-dependent thrombosis by targeting c-Src active autophosphorylation.

BACKGROUND: HIV-infected individuals are known to be at higher risk for thrombotic cardiovascular disease (CVD), which may also be differentially affected by components of anti-HIV drugs. To identify the effects of a series of FDA-approved anti-HIV drugs on platelet aggregation in humans, focusing on the novel pharmacological effects of rilpivirine (RPV), a reverse transcriptase inhibitor, on platelet function both in vitro and in vivo and the mechanisms involved. METHODS AND RESULTS: In vitro studies showed that RPV was the only anti-HIV reagent that consistently and efficiently inhibited aggregation elicited by different agonists, exocytosis, morphological extension on fibrinogen, and clot retraction. Treatment of mice with RPV significantly prevented thrombus formation in FeCl3-injured mesenteric vessels, postcava with stenosis surgery, and ADP -induced pulmonary embolism models without defects in platelet viability, tail bleeding, and coagulation activities. RPV also improved cardiac performance in mice with post-ischemic reperfusion. A mechanistic study revealed that RPV preferentially attenuated fibrinogen-stimulated Tyr773 phosphorylation of ß3-integrin by inhibiting Tyr419 autophosphorylation of c-Src. Molecular docking and surface plasmon resonance analyses showed that RPV can bind directly to c-Src. Further mutational analysis showed that the Phe427 residue of c-Src is critical for RPV interaction, suggesting a novel interaction site for targeting c-Src to block ß3-integrin outside-in signaling. CONCLUSION: These results demonstrated that RPV was able to prevent the progression of thrombotic CVDs by interrupting ß3-integrin-mediated outside-in signaling via inhibiting c-Src activation without hemorrhagic side effects, highlighting RPV as a promising reagent for the prevention and therapy of thrombotic CVDs.

Deoxynivalenol upregulates hypoxia-inducible factor-1α to promote an "immune evasion" process by activating STAT3 signaling.

Trichothecene mycotoxin deoxynivalenol (DON) negatively regulates immune response by damaging host immune system and harming the organism's health. We hypothesized that DON can initiate an active immunosuppressive mechanism similar to "immune evasion" to alter the cellular microenvironment and evade immune surveillance. We tested this hypothesis using the RAW264.7 macrophage model. DON rapidly increased the expression of immune checkpoints PD-1 and PD-L1, inflammatory cytokine TGF-ß, and key immune evasion factors STAT3, VEGF, and TLR-4, and caused cellular hypoxia. Importantly, hypoxia-inducible factor-1α (HIF-1α) acts as a key regulator of DON-induced immunosuppression. HIF-1α accumulated in the cytoplasm and was gradually transferred to the nucleus following DON treatment. Moreover, DON activated HIF-1α through STAT3 signaling to upregulate downstream signaling, including PD-1/PD-L1. Under DON treatment, immunosuppressive miR-210-3p, lncRNA PVT1, lncRNA H19, and lncRNA HOTAIR were upregulated by the STAT3/HIF-1α axis. Moreover, DON damaged mitochondrial function, causing mitophagy, and suppressed immune defenses. Collectively, DON triggered RAW264.7 intracellular hypoxia and rapidly activated HIF-1α via STAT3 signaling, activating immune evasion signals, miRNAs, and lncRNAs, thereby initiating the key link of immune evasion. This study offers further clues for accurate prevention and treatment of immune diseases caused by mycotoxins.

Corrigendum: Identification of microtube-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction.

[This corrects the article DOI: 10.3389/fgene.2022.1092678.].

Differential analysis of immune reconstitution after allogeneic hematopoietic stem cell transplantation in children with Wiskott-Aldrich syndrome and chronic granulomatous disease.

Objective: To investigate similarities and differences in immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). Method: We retrospectively analyzed the lymphocyte subpopulations and the serum level of various immune-related protein or peptide on Days 15, 30, 100, 180 and 360 post-transplantation in 70 children with WAS and 48 children with CGD who underwent allo-HSCT at the Transplantation Center of the Department of Hematology-Oncology, Children's Hospital of Chongqing Medical University from January 2007 to December 2020, and we analyzed the differences in the immune reconstitution process between the two groups. Results: ① The WAS group had higher lymphocyte subpopulation counts than the CGD group. ② Among children aged 1-3 years who underwent transplantation, the WAS group had higher lymphocyte subpopulation counts than the CGD group. ③ Further comparisons were performed between children with non-umbilical cord blood transplantation (non-UCBT) and children with umbilical cord blood transplantation (UCBT) in the WAS group. On Day 15 and 30 post-transplantation, the non-UCBT group had higher B-cell counts than the UCBT group. On the remaining time points post-transplantation, the UCBT group had higher lymphocyte subpopulation counts than the non-UCBT group. ④ Comparisons were performed between children with non-UCBT in the WAS group and in the CGD group, the lymphocyte subpopulation counts were higher in the WAS group compared to the CGD group. ⑤ On Day 100 post-transplantation, the CGD group had higher C3 levels than the WAS group. On Day 360 post-transplantation, the CGD group had higher IgA and C4 levels than the WAS group. Conclusion: ① The rate of immunity recovery was faster in children within the WAS group compared to those children within the CGD group, which may be attributed to the difference of percentage undergoing UCBT and primary diseases. ② In the WAS group, the non-UCBT group had higher B-cell counts than the UCBT group at Day 15 and 30 post-transplantation, however, the UCBT group had higher B-cell counts than the non-UCBT group at Day 100 and 180 post-transplantation, suggesting that cord blood has strong B-cell reconstitution potentiality after transplantation.

HPV vaccine information, knowledge, attitude, and recommendation intention among male college students in China.

This study aimed to describe the status quo of human papilloma virus (HPV)-related knowledge and attitude among Chinese male college students and explore the factors influencing HPV vaccination intention. A national, cross-sectional online survey was conducted among male college students in China to investigate their HPV-related information, knowledge, attitudes, and vaccine recommendation intentions. Path analysis based on the information, knowledge, attitude, and intention model was used to assess the relationships between predictors. In total, 823 male college students participated in the survey. More than 80% of the respondents believed that the HPV vaccine was necessary for their female partners, whereas 136 (16.52%) respondents knew nothing about HPV or HPV vaccines. Information exposure was a positive predictor of HPV-related knowledge. Knowledge subsequently had a positive impact on trust in HPV vaccines, and sufficient knowledge and a positive attitude increased the intention to recommend HPV vaccination (p < .001). Among the demographic characteristics, age and a major in medicine were positively associated with the information score (p < .05). The male college students' HPV-related knowledge was inadequate and negatively influenced their vaccine recommendation intentions. If we take advantage of the Internet and individual sources to increase students' exposure to information, we will improve their HPV-related knowledge and attitudes; thus, the intention to recommend HPV vaccination will ultimately be stronger.

Solitary Interdigital Condyloma Latum in a Female Adolescent: A Case Report of an Unusual Form of Secondary Syphilis.

Condylomata lata are flat-topped, moist papules or plaques usually found in the anogenital area as cutaneous manifestations of secondary syphilis. Here, we present a unique case of a solitary interdigital condyloma latum of secondary syphilis in a 16-year-old female sex worker without other cutaneous findings. Sexual contact history, histopathology, including direct detection of Treponema pallidum, and serological tests were essential for the diagnosis of this case. The patient reached serological cure with two doses of intramuscularly delivered penicillin G benzathine. Owing to the dramatic rise in the incidence of primary and secondary syphilis, medical workers should be aware of the atypical skin manifestations of secondary syphilis in adolescents who are at risk of acquiring sexually transmitted diseases to avoid the progression to late syphilis and further transmission to sexual partners.

Inhibition of Integrin αvß3-FAK-MAPK signaling constrains the invasion of T-ALL cells.

The role of adhesion receptor integrin αvß3 in T-ALL was unclear. Firstly, we performed quantitative real-time PCR to assess medullary expression of integrin ß3(ITGB3) in T-ALL patients and high ITGB3 expression was relevant with the central nervous system leukemia(CNSL) incidence. Decreasing of cell invasion was observed in Jurkat and Molt4 treated with integrin αvß3 specific antibody and inhibitor as well as cells with ITGB3 interference. Further, phosphorylation of FAK, cRAF, MEK and ERK decreased in cells with integrin αvß3 inhibition or interference. Invasion decreased in T-ALL cells treated with FAK and ERK inhibitors. In conclusion, inhibition of integrin αvß3 signals significantly limits the cell invasion of T-ALL cells.

HPV Vaccine Hesitancy and Influencing Factors among University Students in China: A Cross-Sectional Survey Based on the 3Cs Model.

The burden of disease caused by cervical cancer ranked second among female tumors in China. The HPV vaccine has been proven to be a cost-effective measure to prevent cervical cancer, but the vaccination rate remained low to date among university students. This study aimed to understand the status quo of HPV vaccine hesitancy among university students across China during the COVID-19 pandemics and systematically analyze determinants of HPV vaccine hesitancy based on the WHO 3Cs model. Cross-sectional data were collected using an online survey of female university students in four cities across China in June 2022. Multinomial logistic regression was adopted to determine factors influencing vaccine hesitancy based on the 3Cs model with three dimensions, namely complacency, convenience, and confidence. Among 1438 female university students surveyed in this study, 89.7% did not hesitate to vaccinate against HPV, only 8.9% hesitated to some extent, and 1.4% refused to vaccinate. The actual vaccination rate for the HPV vaccine was 34.2%. Based on the 3Cs model, this study found that the trust on the efficacy of vaccines, risk perception of being infected by HPV, price, and distance/time were influencing factors of vaccine hesitancy. Knowledge of the HPV vaccine and sociodemographic characteristics, such as education levels, were also statistically relevant. Therefore, it is recommended that relevant scientific knowledge on cervical cancer and the HPV vaccine should be spread on campus, the vaccination appointment procedure should be simplified, and the affordability of vaccination should be increased through strategic purchasing or providing subsidies, so as to reduce HPV vaccine hesitancy.

Modeling the Health and Economic Burden of Chronic Obstructive Pulmonary Disease in China From 2020 to 2039: A Simulation Study.

OBJECTIVES: Despite a growing prevalence of respiratory diseases in recent decades in China, limited evidence is available on the health and economic burden of chronic obstructive pulmonary disease (COPD). We estimated the 20-year health and economic burden of COPD in China from 2020 to 2039. METHODS: We created a probabilistic dynamic open-cohort Markov model of COPD for the Chinese population aged ≥40 years. Projections of population growth and urbanization rates were obtained from the United Nations Population Division. Other parameter inputs including smoking prevalence, COPD prevalence and severity distributions, disease-related costs, and utility weights were obtained from the most recent published literature. We modeled number of COPD patients, excess mortality due to COPD, exacerbations, COPD-attributable losses of quality-adjusted life-years, and direct and indirect COPD costs over the 20 years. RESULTS: The number of COPD patients was projected to increase from 88.3 million in 2020 to 103.3 million in 2039. The projected total losses of quality-adjusted life-years and the excess mortality due to COPD were, respectively, estimated to be 253.6 million and 3.9 million over the 20 years. The projected 20-year total discounted direct and indirect costs of COPD were, respectively, $3.1 trillion and $360.5 billion. The projected health and economic burden was higher in males and urban areas. CONCLUSIONS: COPD is projected to inflict a substantial burden to the society and the health care system in China. Effective strategies for prevention and early management of COPD are needed to mitigate the forthcoming disease burden.

[Clinical effect of allogeneic hematopoietic stem cell transplantation in children with hyper-IgM syndrome]. / å¼‚åŸºå› é€ è¡€å¹²ç»†èƒžç§»æ¤æ²»ç–—å„¿ç«¥é«˜IgM综合征的临床分析.

OBJECTIVES: To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM). METHODS: A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT. RESULTS: After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (P=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (P<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (P=0.02) and DFS rate (P=0.04). CONCLUSIONS: Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.

Signal transducer and activator of transcription 3 signaling in tumor immune evasion.

The underlying mechanism of tumor immune evasion is a highly concerning subject for researchers. Increasing evidences reveal that the over-activated signal transducer and activator of transcription 3 (STAT3) is a crucial molecular hub in malignant tumors. STAT3 controls autophagy molecules that impair CTL-mediated tumor cell lysis, inhibiting natural killer cells and inducing apoptosis in T lymphocytes to create an immunosuppressive environment. STAT3 signaling regulates the expression of immune factors and recruits immunosuppressive cells to establish a tolerant tumor microenvironment (TME). STAT3 signaling regulates the expression of immune factors and recruits immunosuppressive cells to create an immunosuppressive environment. All this aid tumor cells in escaping from immune surveillance. In this review, we outlined the STAT3-mediated mechanisms involved in tumor immune evasion and their potential regulatory functions in the TME. We discussed the impact of STAT3 signaling on PD-L1, HIF-1α, exosome, lncRNA, and autophagy in the promotion of tumor immune evasion and highlighted the recent research on STAT3 signaling and tumor immune evasion that may assist in developing effective STAT3-targeted drugs for advancing immunotherapy.