OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） combined with neoadjuvant chemotherapy in the treatment of early triple-negative breast cancer （TNBC）. METHODS Randomized controlled trials （RCTs） comparing ICIs combined with neoadjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy alone （control group） were retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， Wanfang Data， and VIP databases， as well as relevant studies published at oncology academic conferences. The search period was from database inception to June 30， 2025. After literature screening， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 6 RCTs involving 3 786 patients were finally included. The meta-analysis results showed that the experimental group had superior event-free survival [HR＝0.73， 95%CI （0.62， 0.85）， P＜0.000 1]， overall survival [HR＝0.69， 95%CI （0.57， 0.84）， P＝0.000 3]， and pathological complete response （pCR） [OR＝1.57， 95%CI （1.37， 1.80）， P＜0.000 01] compared to the control group. The incidence of ≥grade 3 adverse event （AE）， severe AE （SAE）， and ≥ grade 3 immune-related adverse event （irAE） in the experimental group was significantly higher than that in the control group. There was no statistically significant difference between the two groups in the incidence of any AE or any irAE （P＞0.05）. Subgroup analysis revealed that， regardless of programmed cell death ligand 1 expression status （negative or positive），the pCR in the experimental group was significantly higher than that in the control group （P＜0.05）. Additionally， the pCR of the patients with positive lymph nodes in the experimental group was significantly higher to that in the ontrol group （P＜0.05）. There was no statistically significant difference in pCR between the two groups with negative lymph nodes （P＝0.09）. CONCLUSIONS ICIs combined with neoadjuvant chemotherapy can significantly improve event-free survival and overall survival in patients with TNBC， providing patients with long-term survival benefits. However， the risk of ≥ grade 3 AE， SAE and ≥ grade 3 irAE has increased.

AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.

Objective: To investigate the changing trends for associations of anxiety and depressive symptoms with smartphone addiction among middle school students, so as to provide a scientific basis for preventing smartphone addiction in middle school students. Methods: From 2022 to 2023, a method of combining convenient sampling with cluster sampling was used to select 8 923 middle school students from 27 junior high schools and 3 senior high schools in a district of Shenzhen City between September 2022 (baseline, T1) and September 2023 (follow up, T2). The Smartphone Addiction Scale-Short Version (SAS-SV), Patients Health Questionnaire-9 Item (PHQ-9), and Generalized Anxiety Disorder 7-item Scale (GAD-7) were administered to assess smartphone addiction, anxiety and depressive symptoms. Mixed effects models were used to analyze the association of anxiety and depressive symptoms with smartphone addiction among middle school students. Results: From September 2022 to September 2023, the reported prevalence of smartphone addiction increased from 24.22% to 25.25% ( χ 2=45.71); and smartphone addiction scores [ 24.00 (16.00, 32.00),25.00(16.00, 33.00)], anxiety symptom scores [2.00(0.00, 7.00),3.00(0.00, 7.00)] and depressive symptom scores[3.00(0.00, 8.00),5.00(0.00, 9.00)] all significantly increased ( Z =-17.43, -42.38, -41.57) (all P <0.05). There were statistically significant difference in the distribution of anxiety and depression symptom levels among middle school students in 2022 and 2023 ( χ 2=85.15, 106.85, both P <0.05). After adjusting for covariates such as age, gender and family background, mixed effects models revealed dose response associations of anxiety and depressive symptoms with smartphone addiction among middle school students:mild anxiety symptom( OR =3.22), moderate to severe anxiety symptom ( OR =5.36), mild depressive symptom ( OR =3.32) and moderate to severe depressive symptom ( OR =6.13) were significantly associated with higher risks of smartphone addiction (all P <0.05). Interaction effect analysis found that co existing anxiety and depressive symptoms synergistically increased addiction risk by 5.60 times ( OR =5.60) compared to the asymptomatic group, with 32% of the combined risk attributable to their interaction ( S=1.64, AP =0.32)(both P < 0.05 ). Conclusions Anxiety and depressive symptoms are significantly associated with smartphone addiction, exhibiting a synergistic effect. Attention should be paid to emotional issues and smartphone addiction among middle school students.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

ObjectiveTo analyze the correlation between the clinical symptoms， signs， syndrome characteristics and laboratory indicators of cough variant asthma （CVA） and deepen the understanding of the treatment of this disease based on the theory of "Fu Feng". MethodsAn observational study was conducted. A total of 207 CVA patients who visited the respiratory department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from September 2022 to November 2023 were included. The information from the four diagnostic methods and the laboratory test results of patients were collected. Factor analysis was conducted on the information obtained through the four diagnostic methods in TCM， and the nature and location of CVA were extracted. Sample cluster analysis （Q clustering） and the K-means method were used for data clustering analysis to determine the syndrome types of CVA and analyze the syndrome characteristics and differences in laboratory indicators among different syndrome types. ResultsThe main symptom of CVA patients was cough， accompanied by symptoms such as itchy throat， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， chest tightness， hoarseness， bitter mouth， poor appetite， and skin itching. Factor analysis showed that the disease was located in the lung， involving the liver， spleen， and kidney. The pathological factors involved Yin deficiency， Yang deficiency， wind factor， dampness factor， Yin factor， and Qi stagnation. Cluster analysis revealed four syndrome types： Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. Fengfu Yinshang syndrome accounted for the highest proportion， followed by Tanyin Zufei syndrome. There were no significant differences in eosinophil count and percentage， fractional nasal nitric oxide （FnNO） level， and pulmonary function indexes among the four syndromes. The levels of serum total IgE and fractional exhaled nitric oxide （FeNO） in patients with Fengfu Yinshang syndrome were significantly higher than those in patients with Shixie Neiyun syndrome and Tanyin Zufeisyndrome. ConclusionCough is the main symptom of CVA， accompanied by pharyngeal itching， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， and allergic manifestations. The disease involves the lung， liver， spleen， and kidneys. The essence of the pathogenesis lies in a latent dormant pathogen and a disorder of the pivot mechanism. The four common syndrome types are Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. The TCM syndrome types are correlated with laboratory indexes. The serum total IgE and FeNO of patients with Fengfu Yinshang syndrome are worse.

Purpose To compare the HRCT findings of lung damage in patients with idiopathic inflammatory myopathies(IIMs)with positive and negative anti-Ro-52 antibody.Materials and Methods Fifty patients with IIMs admitted to Beijing Shijitan Hospital,Capital Medical University from January 2015 to July 2023 were retrospectively analyzed.The patients were divided into anti-Ro-52 antibody negative group(18 cases)and positive group(32 cases),the lung CT findings of the two groups were compared,the distribution of lung lesions and related signs were analyzed.Results The incidence of interstitial lung disease in the anti-Ro-52 antibody-negative group was 11.1%(1 case),which was lower than that in the positive group 75.6%(31 cases)(P=0.001).Among the interstitial lung disease-positive patients,the proportion of lesions in the anti-Ro-52 positive group was more symmetrical(28 cases,87.5%,P=0.022)and peripheral distribution(20 cases,62.5%,P=0.039)than that in the anti-Ro-52 negative group.Non-specific interstitial pneumonia-like lesions were the main lesions in the two groups,including 14 cases(43.8%)in the anti-Ro-52 positive group and 7 cases(38.9%)in the negative group.However,9 cases(28.1%)of the anti-Ro-52 positive group had acute interstitial pneumonia-like lesions and 1 case(5.6%)of the negative group had acute interstitial pneumonia-like lesions.Imaging accompanying signs:anti-Ro-52 positive combination and consolidation(14 cases,43.8%,P=0.009),nodular shadow(17 cases,53.1%,P=0.025),and reverse halo sign(12 cases,37.5%,P=0.021)were more than those in the anti-Ro-52 negative group.Conclusion IIMs patients with positive anti-Ro-52 antibody have a higher incidence of interstitial lung disease.HRCT findings are of great significance for diagnosis and treatment of IIMs.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

OBJECTIVE To analyze the clinical characteristics of the 12 patients tested with Candida auris in a three-A hospital so as to provide guidance for prevention and control of nosocomial C.auris infection.METHODS The specimens sources and departments where the C.auris strains were isolated as well as the drug resistance were retrospectively collected from Zhongda Hospital Affiliated to Southeast University between Sep.2023 and Jun.2024.The clinical characteristics of the patients with C.auris infection were summarized.The epidemiological survey was conducted for the possibility of its transmission in hospitals,and the corresponding modified preven-tion measures were put forward.RESULTS Among the 12 patients who were tested with C.auris,10 were male,and 2 were female;the age ranged between 21 and 92 years old.Most of the patients were complicated with multi-ple underlying diseases and had the history of repeated hospitalization as well as the history of invasive operation procedures such as tracheotomy,urinary catheterization,gastric tube indwelling and venoarterial catheterization;in the meantime,other multidrug-resistant organisms(MDROs)and fungi were tested in those patients,and the patients used multiple types of antibiotics.Totally 16 strains of C.auris were isolated from the 12 patients with C.auris tested,62.50％(10/16)of which were isolated from urine specimens,18.75％(3/16)were isolated from sputum specimens,and 6.25％(1/16)were isolated from deep venous catheter,tissue biopsy and wound swab specimens.All of the 16 strains of C.auris were resistant to fluconazole and sensitive to caspofungin;4 strains were resistant to amphotericin B.Totally 2 patients had Candida auris infection,one was pulmonary infection,and the other was urinary tract infection,and the infection rate was 16.67％;both patients were cured.There were 10 cases of colonization,and the colonization rate was 83.33％.The result of epidemiological survey indicated that the C.auris that was tested in the No.8 patient may originate from the No.4 patient who carelessly brought from outside the hospital due to poor implementation of standardized prevention measures.CONCLUSIONS The patients tested with C.auris usually have complicated medical backgrounds.Although the colonized C.auris strains are dominant among the strains in the hospital,the related departments need to intensify the implementation of pre-vention measures so as to prevent the transmission of C.auris and pay special attention to the early identification and management of imported pathogens.

Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter P_gapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD₆₀₀ value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods* ; Escherichia coli/metabolism* ; Promoter Regions, Genetic/genetics* ; Green Fluorescent Proteins/metabolism* ; Transcription Factors/genetics* ; Escherichia coli Proteins/genetics* ; Diamines/metabolism* ; Gene Expression Regulation, Bacterial

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.