Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Diffuse large B-cell lymphoma(DLBCL)is an aggressive disease that exhibits high heterogeneity in terms of biology,clinical manifestations,and prognosis.The tumor microenvironment(TME)plays a crucial role in supporting tumor cell survival.Exploring the TME is of great significance for revealing the occurrence and development of DLBCL,guiding clinical treatment,and predicting prognosis.Multiplex immunofluorescence(mIF)is one of the methods for investigating the TME.mIF can directly perform staining and labeling on tissue sections,retaining the orig-inal spatial structure of DLBCL tissues.mIF not only quantifies the expression levels of markers but also relatively ac-curately identifies the types of different cells,revealing the spatial distribution and interactions of various cells.In addi-tion,its exploration of the expression and role of immune checkpoints cannot be ignored.In this review,the current ap-plication of mIF in DLBCL TME studies is reviewed,which provides a broader perspective for the characterization of DLBCL TME and opens up new ideas for exploring potential therapeutic targets and prognostic markers in DLBCL pa-tients.

Objective:To quantitatively summarize the catechol-O-methyltransferase ( COMT) gene Val158Met polymorphism and the risk of obsessive-compulsive disorder (OCD). Methods:We searched databases including PubMed, Embase, Weipu and Wanfang for randomized controlled trials (RCTs) investigating the association between COMT gene polymorphisms and OCD up to November 1, 2023. Studies that reported genotype frequencies for both OCD patients and general healthy controls were included. Stata11 software was used to calculate pooled odds ratios ( OR) with 95% CI, perform heterogeneity test, and assess publication bias. Results:19 studies with 2, 393 OCD patients and 4, 134 healthy controls were included. The overall results showed that the Val158Met polymorphism was associated with OCD patients (allele model: OR=1.10, 95% CI: 1.02-1.20, P=0.016; homozygote model: OR=1.25, 95% CI:1.05-1.49, P=0.014; recessive model: OR=1.18, 95% CI:1.01-1.37, P=0.040). In the ethnic-stratified analysis, this significant association was mainly observed in Caucasians (allele model: OR=1.17, 95% CI:1.06-1.30, P=0.003; homozygote model: OR=1.35, 95% CI: 1.08-1.67, P=0.008; recessive model: OR=1.21, 95% CI: 1.01-1.44, P=0.041; dominant: OR=1.20, 95% CI: 1.01-1.43 P=0.040), but not in Asians. In gender-stratified analysis, Met-homozygote was associated with male OCD ( OR=1.75, 95% CI: 1.00-3.04, P=0.049). Moreover, the additional analysis found that the risk of OCD was significantly increased in Caucasian males (allele model: OR=1.48, 95% CI: 1.08-2.03, P=0.014; heterozygote model: OR=1.41, 95% CI: 1.03-1.93, P=0.030; dominant model: OR=1.60, 95% CI:1.08-2.38, P=0.020). Conclusion:This meta-analysis suggests that the COMT gene Val158Met polymorphism is associated with an increased risk of OCD in males, particularly in Caucasian males.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Thyroid cancer is the most common endocrine malignancy. Although most patients achieve good prognosis through surgery and conventional treatments, approximately 15%-20% of patients with papillary thyroid cancer and the anaplastic and medullary thyroid cancers still lack effective treatment options. The tumor immune microenvironment plays a critical role in the occurrence, progression, and drug resistance of thyroid cancer. This review focused on the key immune cells in thyroid cancer, including tumor-associated macrophages, myeloid-derived suppressor cells, mast cells, natural killer cells, and T lymphocytes, and explored their roles and mechanisms in tumor immune evasion. Immunotherapy has become an emerging treatment strategy for advanced thyroid cancer, we summarized the attempts and advances in immune checkpoint inhibitors, targeted macrophage therapy and tumor vaccines.

Objective To conduct a visual analysis of research hotspots and development trends in stress ulcer(SU)from 2004 to 2024 using CiteSpace software.Methods Relevant SU literature published between January 1,2004,and May 7,2024,was retrieved from the Web of Science data-base and analyzed visually using CiteSpace software.Results A total of 623 articles were included in this study.The number of publications followed a wavy increase trend from 2004 to 2024.The au-thor with the highest number of publications was MOLLER M H,the institution with the most publica-tions was Copenhagen University Hospital in Denmark,and the country with the most publications was China.Keyword analysis revealed that SU research primarily focused on exploring pathogenesis and developing prophylactic and therapeutic drugs.Conclusion The pathogenesis of SU needs further elucidation.Research on drugs and prevention tailored to different mechanisms inducing SU,the im-pact of enteral nutrition on patient prognosis,and the effectiveness of traditional Chinese medicine in prevention and treatment are hotspots and development trends in future research.

Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.

Objective:To establish a rapid detection method based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)for drug resistance of Carbapenem-resistant Enterobacteriaceae(CRE),so as to provide basis for enhancing clinically diagnostic effect.Methods:A total of 120 suspected CRE strains that were isolated from the clinical laboratory of Jiading District Central Hospital Affiliated to Shanghai University of Medicine&Health Sciences during October 2023 and September 2024 were collected,and the experimental detection of 44 strains was finally completed.The 44 suspected CRE bacterial strains were all from hospitalized patients.A rapid detection protocol based on the MALDI-TOF MS platform was initially established and improved,and experimental detection was carried out using the fully automatic rapid microbial mass spectrometry detection system(VITEK MS).The results of identification review and antimicrobial susceptibility test(AST)for VitEK-2 Compact strain was used as the reference standard.The screening results and detection efficacy of two kinds of detection methods were compared.Results:In the 44 suspected CRE strains,31 CRE strains were screened out by MALDI-TOF MS detection,and 31 CRE stains were screened out by VITEK-2 Compact recheck detection.In them,one strain of Enterobacter cloacae was confirmed as negativity by the MALDI-TOF MS test,but it was confirmed as CRE by the VITEK-2 Compact test.One strain of Klebsiella pneumoniae was confirmed as positivity by the MALDI-TOF MS test,but it was confirmed as mediator for carbapenem drugs by the VITEK-2 Compact test.The tested results of VITEK-2 Compact was used as standard,the results of four-grid table(2×2 contingency table)statistical method indicated that the sensitivity,specificity,accuracy rate and Youden index(R)of MALDI-TOF MS were respectively 96.7%,92.3%,100%and 89.1%.Conclusion:The rapid detection method based on the MALDI-TOF MS platform for CRE drug resistance has simple operation process and high accuracy rate,which can provide a basis for the application of targeted antibacterial drugs at early stage.