ObjectiveThe present study aimed to analyze the efficacy and safety of letermovir for preventing cytomegalovirus (CMV) infection and its impact on immune reconstitution in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsThe retrospective analysis included 83 patients who underwent allo-HSCT at Shanghai Children’s Hospital between January 2022 and June 2025 and survived ≥100 days post-transplantation. Forty patients received letermovir as primary CMV prophylaxis (letermovir group), and 43 patients did not receive prophylaxis (control group). The primary outcomes were the post-transplantation incidence of CMV infection and CMV disease. Secondary outcomes included the effects of letermovir on acute graft-versus-host disease (aGVHD), hematopoietic reconstitution (time to neutrophil and platelet engraftment), liver function, incidences of Epstein-Barr virus (EBV) and BK virus (BKV) infections, and cellular immune reconstitution.ResultsThe cumulative incidence of CMV infection post-transplantation was significantly lower in the letermovir group than in the control group (100 days: 7.5% vs. 53.5%, p<0.001; 180 days: 12.5% vs. 53.5%, p<0.001). No CMV disease occurred in either group. CMV reactivation occurred in 3 patients (7.5%) after discontinuation of letermovir. In the letermovir group, CMV infection occurred later [mean (range): 90.7 (31–168) days vs. 42.7 (16–90) days, p=0.050], lasted for a shorter duration [11.8 (7–15) days vs. 17.5 (4–39) days, p=0.042], and had a lower mean viral load [3,175 copies/ml vs. 30,407 copies/ml, p=0.393]. No significant differences were observed between the two groups in the time to neutrophil and platelet engraftment, incidence of grade II–IV and III–IV aGVHD, incidence of liver function abnormalities, or rates of EBV/BKV infection. Multivariate analysis showed that letermovir prophylaxis was an independent protective factor against CMV infection within 100 days post-transplantation (hazard ratio: 0.127, p=0.001). At 90 days, 180 days, and 1 year post-transplantation, the T lymphocyte and B lymphocyte counts were significantly lower in the letermovir group than in the control group (p<0.05). By 1 year post-transplantation, there was no difference in NK cell counts between the two groups (p=0.094). Within the letermovir group, only CD8+ T cell counts were significantly increased 1 year post-transplantation compared to pre-transplantation (p=0.027).ConclusionLetermovir is safe and effective at reducing the risk of CMV infection in children after allo-HSCT, significantly delaying the onset of infection and shortening its duration. Although letermovir may impact early lymphocyte subset reconstitution, immune function can recover to pre-transplantation levels by 1 year post-transplantation.

Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron’s papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.

OBJECTIVES:To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors. METHODS:A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022. RESULTS:The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (P<0.05). The children with platelet count >400×109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (P<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (P>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (P<0.05). CONCLUSIONS:The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×109/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.

BACKGROUND Hereditary spherocytosis (HS) is characterized by anemia, jaundice, splenomegaly, and cholelithiasis, and is caused by abnormal genes encoding red blood cell membrane components. The most common mutations found in HS are in the ANK1 gene. CASE SUMMARY A 4-mo-old girl was admitted to our hospital with pallor that had lasted for more than 2 mo. She presented with jaundice, anemia and splenomegaly. A heterozygous mutation of ANK1 (exon23: c.G2467T:p.E823X) was identified, and the mutation was determined to be autosomal dominant. This mutation is linked to the relatively serious anemia she had after birth; this anemia improved with age. CONCLUSION The utilization of next-generation sequencing may assist with the accurate diagnosis of HS, especially in atypical cases.

Resveratrol is a representative polyphenol of diet-derived putative cancer chemopreventive agents, which have attracted increasing interest in the cancer chemoprevention community. The inhibition of the action of human papillomavirus (HPV) E6 and E7 has been considered a key approach for cervical cancer therapy. Resveratrol has been shown to induce the apoptosis, and reduce both the viability and mitotic index of a number of cancer cell lines, including human cervical cancer cells. In the present study, it was confirmed that resveratrol inhibited the HPV E6 mRNA, HPV E6 protein and phosphorylated retinoblastoma protein (p-pRb1) levels, and increased the p53 protein levels in HeLa and Ca Ski cells, as well as in subcutaneous tumor tissue grown from HeLa cells. High-risk HPV uses a bicistronic RNA to control E6 and E7 genes simultaneously. On the whole, the present study demonstrates that resveratrol inhibits cervical cancer development by suppressing the transcription and translation of E6 and E7, and also by promoting the apoptosis and G1/S phase transition arrest. These findings may provide the basis for the development of resveratrol as a candidate for cervical cancer therapy.

Trans -resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo . Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.

外泌体（exosomes）是由细胞释放至胞外的膜性囊泡，直径40~100nm。外泌体可介导细胞间信息传递和物质交换，在疾病的发生发展中发挥着重要作用。在病毒感染过程中，外泌体既可传递病毒核酸、RNA和蛋白质，又可传递抗病毒分子引起免疫应答。通过对外泌体的深入研究，可在病毒感染临床治疗中提供新前景。

目的 探讨miR-374-5p靶向B细胞淋巴瘤(Bcl)-2相关X蛋白(Bax)对缺氧诱导心肌细胞凋亡的分子机制.方法 检测常氧和缺氧条件下大鼠心肌细胞H9c2和CP-R073中miR-374-5p的表达.以H9C2细胞缺氧处理建立细胞模型,随机分为H9c2常氧培养组、H9c2缺氧培养组、缺氧+miR-374-5p组、缺氧+miR-NC组、缺氧+miR-374-5p+pcDNA3.1-Bax组和缺氧+miR-374-5p+pcDNA3.1组.qRT-PCR检测各组H9c2中miR-374-5p的表达;四甲基偶氮唑蓝(MTT)比色法检测细胞增殖活力;流式细胞术检测细胞凋亡;Western印迹检测Bax、Bcl-2、细胞周期蛋白(Cyclin)D1和p21蛋白的表达.双荧光素酶报告基因分析法验证miR-610对ORC1的靶向作用.结果 在缺氧条件下,大鼠心肌细胞H9c2和CP-R073中miR-374-5p的表达显著下降(P<0.05).过表达miR-374-5p可抑制缺氧诱导的H9c2细胞凋亡(P<0.05).Bax是miR-374-5p的靶基因,miR-374-5p负向调控Bax的表达.过表达Bax可逆转miR-374-5p对缺氧诱导的H9c2细胞凋亡的抑制作用.结论 miR-374-5p可通过靶向下调Bax抑制缺氧诱导的心肌细胞凋亡.

Escherichia coli is an opportunistic bacterial pathogen that causes a wide range of nosocomial infections. The emergence of multidrug resistance in E. coli poses a severe threat to global health. Phage therapies are an alternative method to control multidrug-resistant pathogens, which have been attracting increasing attention. Owing to their ability to lyse bacteria specifically and efficiently, bacteriophages are considered novel antimicrobial agents. In this study, we used multidrug-resistant E. coli as an indicator and isolated, characterized, and compared two new phages of the Siphoviridae family referred to as vB_EcoS_XF and vB_EcoS_XY2. These phages were able to infect several pathogenic multidrug-resistant E. coli strains. A short latent period and large burst size ensured their rapidly reproduction in host cells. Their tolerance of high temperatures and high pH levels meant that remained stable when used to control pathogenic E. coli strains. No obvious cytotoxicity was observed when either HEK293 T or A549 cells were incubated with these two phages. Mass spectrometry analysis allowed us to identify several phage-encoded proteins. Genomic analysis revealed that no toxic proteins or antibiotic proteins were encoded. Genome comparison and phylogenetic analysis indicated that the phages identified show high similarity with E. coli phages of the genus Kagunavirus. The desirable characteristics of the novel phages identified make them good potential therapeutic candidates, and components of phage cocktails to treat multidrug-resistant E. coli in the future.

A virulent phage, named vB_EcoS_XY3, was isolated from hospital wastewater in Xiangyang, China. Its morphological characteristics, growth parameters, adsorption rate, and pH and temperature stability were determined. Phage vB_EcoS_XY3 was found to be able to infect Escherichia coli laboratory strains and also some multidrug-resistant E. coli strains. Its complete genome consists of 51,345 base pairs of double-stranded DNA with an average GC content of 55.24% and 85 putative protein-coding genes. Forty-four genes were annotated with known functions. These results will not only provide further insights into E. coli phages but also have implications for the development of potential biocontrol agents.

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES-mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial-mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

目的 探讨中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对新型冠状病毒肺炎(COVID-2019)预后的预测价值.方法 采用回顾性分析2020年2月至2020年3月湖北医药学院附属襄阳市第一人民医院救治的COVID-19感染患者20例,根据临床特征及病情分为普通组(包括普通型和轻型10例),重度组(包括重型和危重型10例).收集患者入院后当天、1周后和出院时实验室检测和流式细胞术检测结果,计算NLR、ΔNLR1(入院1周后NLR-入院当天NLR)、ΔNLR2(入院后l周NLR-出院时NLR),比较两组上述指标的差异.流式细胞仪检测两组患者外周血中淋巴细胞、中性粒细胞、单核细胞的散点分布特征,及中性粒细胞表面标记CD15、T细胞活化的标记抗原HLA-DR阳性率.结果 两组的NLR在治疗期间有显著变化,重度组的NLR在治疗1周时升高更明显,治愈出院时,两组患者的NLR都有显著下降.普通组CD15+中性粒细胞频数相对重度组较低,治疗期间没有显著波动,重度组CD15+中性粒细胞频数在治疗1周时明显升高,在治愈出院时显著下降;两组的HLA-DR+T细胞频数在治疗期间均有动态的显著变化,在治疗1周时明显升高,治愈出院时都有显著下降,而且在每个检测时间点都有组间差异.结论 动态监测NLR、CD15+中性粒细胞频数、HLA-DR+T细胞频数可反映COVID-19的病情和预后.

Background: Hirschsprung's disease (HSCR) caused by absence or dysfunction of ganglion cells in the submucosal plexus and intermuscular plexus of the intestinal wall. Studies have shown that homozygous mutations of glial cell-line derived neurotrophic factor ( GDNF ) can lead to the occurrence of HSCR. but heterozygous mutation must combine with other related abnormal genes could to cause the HSCR. The other Guanylyl cyclase C ( GUCY2C ) gene is rarely reported as a direct cause of HSCR. Our findings Provides a new perspective for application of mutation screening in the genetic counseling.Case presentation: We report clinical and genetic findings of a trio pedigree with Hirschsprung's disease. Whole exome sequencing and Sanger sequencing were performed for propositus and all members of trio pedigree, respectively. We also collected 74 healthy control samples and used Sanger sequencing to identify that found the mutation. We first described the rare trio pedigree of HSCR caused by two special genes of GDNF (p.Arg93Gln) and GUCY2C (p.Tyr1072Cys). Studies have found that mutations in GDNF alone do not cause HSCR symptom, so is propositus’ mother in this study. Common mutation of GDNF gene mutation inherited from mother of proband, but the rare mutation of GUCY2C from the father. None of the parents showed HSCR phenotype. We provide evidence for the causative role of the two variants.Conclusions: Our study found that GDNF and GUCY2C together lead to the occurrence of HSCR. This finding expands the genotype spectrum and increases knowledge on the genetic molecular mechanisms of the HSCR. Our findings will provide help for the screening of pathogenic genes of HSCR.

Background Hereditary spherocytosis (HS) is the most common haemolytic anaemia caused by congenital membrane defects of red blood cells. The name derives from the presence of spherical red blood cells in the peripheral blood. Clinical manifestations of HS are anaemia, haemolytic jaundice, and large spleen, and infection can worsen the condition, often with cholelithiasis. HS is mainly caused by abnormal functions of the products of six genes. Splenectomy is the main treatment for HS. Case presentation Half a day after birth, the proband exhibited HS-related symptoms, with progressive aggravation. Routine examination in the outpatient department showed an increase in white blood cells and a decrease in red blood cells. His mother had HS and a partial splenectomy. We suspected that the infant might also have HS. Genomic DNA samples were extracted from the three members of the HS trio pedigree, and genomic whole-exome sequencing (WES) was performed. The three DNA samples were amplified by polymerase chain reaction (PCR), followed by Sanger sequencing to identify mutation sites. A novel nonsense heterozygous mutation, c.790C > T (p. Gln264Ter), in the ANK1 gene, which causes premature termination of translation, was found in this Chinese family with autosomal dominant HS. Conclusions This de novo nonsense mutation can cause the onset of HS in early childhood, with severe symptoms. Expanding the ANK1 genotype mutation spectrum will lay a foundation for the further application of mutation screening in genetic counselling.

随着二代测序的快速推进,组学领域呈现了井喷式的发展.医生已能够根据患者的分子指征,更有针对性进行治疗,医疗从传统的循证医学逐渐的进入到了精准医学的范畴.精准医学强调综合个人的检查数据,在正确的时间,以正确的方式,给予病人正确的治疗.这种转变促使当代的医学研究生的培养模式和方式的改进,同时传统的医学思维方式需要改进以适应精准医疗的逐步发展.