OBJECTIVES: To investigate the causal relationship between Helicobacter pylori (Hp) infection and immune thrombocytopenia (ITP) using Mendelian randomization (MR), as well as the association between Hp infection and chronic ITP (cITP) through a clinical study. METHODS: The datasets from genome-wide association studies were used to select the single nucleotide polymorphism loci significantly associated with Hp infection as genetic instrumental variables. The MR analysis model was used to investigate the causal relationship between ITP and Hp infection. A retrospective analysis was conducted on the medical data of 316 children with newly diagnosed ITP at the First Affiliated Hospital of Xinjiang Medical University from January 2020 to December 2023. The children were followed up for 1 year, and a multivariate logistic regression analysis was used to investigate the risk factors for cITP. RESULTS: The inverse variance weighted analysis revealed that Hp infection was significantly associated with an increased risk of ITP (OR=1.280, 95%CI: 1.098-1.492, P=0.002). There was no heterogeneity or pleiotropy in this MR study (P>0.05), and the model was stable. The "leave-one-out" sensitivity analysis verified the reliability of the results. The multivariate logistic regression analysis demonstrated that Hp infection was an independent risk factor for progression to cITP (OR=7.916, 95%CI: 3.327-18.832, P<0.001). CONCLUSIONS Hp infection is a risk factor for the onset of ITP and is an independent risk factor for cITP in children.
Humans ; Helicobacter Infections/complications* ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Child ; Male ; Female ; Helicobacter pylori ; Prognosis ; Child, Preschool ; Logistic Models ; Retrospective Studies ; Risk Factors ; Polymorphism, Single Nucleotide ; Adolescent ; Infant

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on cognitive function in mice with post-traumatic stress disorder(PTSD).Methods The mice were randomly divided into normal group,model group and experimental group.Except for the normal group,the PTSD mouse model was established by single prolonged stress(SPS).The experimental group was intraperitoneally injected with 10 mg·kg-1 TMP,and the normal group and the model group were intraperitoneally injected with an equal amount of 0.9％NaCl.The Morris water maze,open field and elevated plus maze tests were used to evaluate the cognitive behavior of the mice.The apoptosis of neurons was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of ionized calcium binding adapter molecule-1(Iba-1)protein was detected by immunofluorescence(ICC).The content of oxidative stress inflammatory factors was detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency of the normal group,model group,and TMP group were(56.50±9.89),(87.16±10.48)and(68.63±10.19)s,respectively;the corner residence time of the open field were(190.37±40.64),(260.39±40.54)and(218.63±38.27)s,respectively;the apoptosis rates were(18.28±2.35)％,(39.36±3.65)％and(30.74±3.58)％,respectively;the fluorescence intensities of Iba-1 were(8.01±2.23)％,(50.87±7.31)％and(7.49±1.41)％;malondialdehyde contents were(5.46±0.95),(12.98±2.06)and(8.31±1.28)nmol·mg-1,respectively;tumor necrosis factor-α contents were(53.59±9.91),(115.46±11.53)and(74.38±10.77)pg·mL-1,respectively.The above indexes in the normal group and the experimental group were statistically significant compared with the model group(P＜0.05,P＜0.01).Conclusion TMP can improve the cognitive function of PTSD mice,and the mechanism may be related to the regulation of inflammation and oxidative stress.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

Based on the isolation and identification of Nosema ceranae(N.ceranae)in honeybees,this study optimized the synthesis method of nano-FeS derived from albumen and explored in vitro and in vivo antifungal effects against N.ceranae.Pathogens were isolated from infected honeybee colonies and identified as N.ceranae using morphological and molecular biology techniques.In vitro experiments were conducted to confirm the antifungal effects of nano-FeS against N.ceranae and elucidate the mechanism.In vivo experiments were carried out to validate the therapeutic effects of nano-FeS against N.ceranae infection.Nano-FeS was synthesized using the solvothermal method with an optimal scheme determined through orthogonal experiments,with an average par-ticle size of 75 nm.Flow cytometry and fluorescence staining experiments confirmed that nano-FeS induced apoptosis and necrosis in N.ceranae.After N.ceranae was exposed to nano-FeS,intracellu-lar iron accumulation,disruption of the glutathione and glutathione peroxidase antioxidant system,and subsequent ROS accumulation were observed,ultimately leading to lipid peroxidation of cell membranes.In vivo experiments demonstrated reduced mortality and decreased spore counts in the midgut of honeybees fed with nano-FeS.Transcriptome analysis and qPCR revealed the impact of nano-FeS on gene expression in the N.ceranae infected honeybee midgut.This study presented a promising alternative antifungal agent for N.ceranae infection in honeybees and elucidated the an-tifungal mechanism of nano-FeS related to ferroptosis.Additionally,the study found a positive cor-relation between the mass concentration of nano-FeS and its antifungal effectiveness against N.ceranae.

Objective To explore the effects of polystyrene microplastics(PS-MPs)on the growth,activity,oxida-tive stress levels,biofilm formation and virulence of Klebsiella pneumoniae.Methods Klebsiella pneumoniae was exposed to PS-MPs at different concentrations(10,50 and 100 μg/ml)and particle sizes(0.1,1.0 and 5.0 μm),and the growth curves were measured.The bacterial activity was determined by CCK-8(cell counting kit-8).The level of intracellular reactive oxygen species(ROS)was determined by fluorescence probe.The biofilm forming ability was determined by crystal violet staining.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the relative expression levels of biofilm-forming genes(luxS,mrkA,wbbM,pgaA,wzm)and viru-lence genes(ureA,uge,wabG,fimH).Results A high concentration(100 μg/ml)of 0.1 μm PS-MPs had a stronger inhibitory effect on the growth and activity of Klebsiella pneumoniae,and the intracellular ROS level signifi-cantly increased,indicating that smaller particle size and higher concentration of PS-MPs were more toxic to bacte-ria.PS-MPs of 100 μg/ml particle size groups(0.1,1.0 and 5.0 μm)significantly promoted the biofilm forma-tion of Klebsiella pneumoniae.The relative expression levels of biofilm formation related genes(luxS,mrkA,wbbM,pgaA,wzm)and virulence genes(ureA,uge,wabG,fimH)increased.Conclusion By inducing Kleb-siella pneumoniae to produce a high level of ROS,PS-MPs can cause oxidative stress,inhibit the growth and activi-ty of bacteria,and enhance the biofilm formation ability and virulence,thus affecting the biological characteristics of Klebsiae pneumoniae.

Objective To investigate the therapeutic effect of segmental decompression combined with corrective short-segment fusion surgery for the treatment of degenerative lumbar scoliosis.Methods In total,124 patients with degenerative lumbar scoliosis were selected and divided into short-and long-segment fusion groups using the random number table method,with 62 patients in each group.Posterior short-segment decompression,fixation,and fusion were performed in the short-segment fusion group;the fusion segment was the adjacent lumbar vertebra.Posterior long-segment decompression,fixation,and fusion were performed in the long-segment fusion group;the fusion segments included multiple adjacent lumbar vertebrae.At the 6th month after surgery,the coronal Cobb angle of lumbar convexity,sagittal Cobb angle of lumbar lordosis,intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,spinal canal diameter,Japanese Orthopedic Association(JOA)score,Oswestry Disability Index(ODI),degree of pain in the lower back and lower limbs,and postoperative complications were compared between the groups.Results The Cobb angle of the coronal lumbar scoliosis in the short-and long-segment fusion groups was significantly higher than that before surgery(P<0.05).At the 6th month after surgery,the intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,and spinal canal diameter in both groups increased,and those in the short-segment fusion group were higher than those in the long-segment fusion group(P<0.05);at the 6th month after the operation,the JOA scores of the short-segment and long-segment fusion groups were higher than those before surgery,and the JOA score of the short-segment fusion group was higher than that of the long-segment fusion group(P<0.05).The ODI score was lower than that before surgery in the short-and long-segment fusion groups,and the ODI score in the short-segment fusion group was lower than that in the long-segment fusion group(P<0.05).At the 6th month after surgery,the pain scores of the lower back and lower limbs in the short-and long-segment fusion groups were significantly higher than those before surgery(P<0.05).There were two cases of dural tears during decompression caused by lamina dura adhesion in the long-segment fusion group,and no serious complications were observed in the short-segment fusion group.Conclusions Both short-and long-segment decompression fixation fusion using a posterior approach can achieve good therapeutic effects for treating degenerative lumbar scoliosis.However,compared to the long-segment fusion group,the short-segment fusion group undergoing short-segment decompression fixation fusion through a posterior approach had a shorter surgical period,lower intraoperative blood loss,better recovery of lumbar function,and a lower risk of postoperative complications.