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.

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

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

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

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Methods: Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1, 2020, to October 30, 2021 were enrolled as the research participants in the study. They were assigned to two groups based on traditional Chinese medicine (TCM) syndrome types: heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group. Healthy volunteers who underwent health check-ups in the Health Management Department were included as healthy group following the random number table method. The tears of the patients and the healthy volunteer participants were tested by high-performance liquid chromatography-mass spectrometry (LC-MS). The differential metabolites were screened out by multivariate statistical analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed on the differential metabolites. Finally, the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites. Results: A total of 32 dry eye patients were enrolled, including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern. Fourteen healthy volunteers were included as healthy group. There were no significant differences in baseline characteristics among the three groups (P > 0.05). A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group, mainly including lipids, lipid-like molecules, organic acids and their derivatives, organic heterocyclic compounds, and nucleosides and their analogues. For heat stagnation in liver meridian pattern group, 112 metabolites were determined, mainly including organic acids and their derivatives, lipids, and lipid-like molecules. The KEGG enrichment results of pathways and the relative content analysis of differential markers demonstrate that purine metabolism and caffeine metabolism pathways are common metabolic characteristics of all dry eyes. Among them, deoxyinosine monophosphate (dIMP) and 2-(formamido)-N1-(5-phospha-D-ribosyl) acetamidine can serve as their biomarkers. The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation, ovarian steroidogenesis, cholesterol metabolism, pyrimidine metabolism, and bile secretion (P < 0.05). Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine, leucine, and isoleucine biosynthesis pathways (P < 0.05). Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification. Different patterns of dry eye syndrome exhibit typical characteristics in the types and concentrations of metabolites, which correspond to the syndrome classification in TCM. This study initially confirms the rationality of TCM syndrome classification and provides significant reference for the mechanism of dry eye and drug development.

Objective To investigate the effect and mechanism of melatonin on the epithelial-mesenchymal transition(EMT)of human peritoneal mesothelial cells.Methods A human peritoneal mesoepithelial cell line(HMrSV5)was cultured.Decorin(DCN)overex-pression and knockout plasmids were constructed.The cells were divided into the normal,TGF-β1,TGF-β1+melatonin,TGF-β1+mela-tonin+siDCN,TGF-β1+melatonin+siNC,and TGF-β1+DCN groups.The cell proliferation and survival rates were determined using Cell Counting Kit-8(CCK-8).The protein and mRNA expression levels of DCN,TGF-β1,Smad2,and E-cadherin were detected by Western blotting and real-time polymerase chain reaction(PCR),respectively.Results The CCK-8 assay showed that the cell survival rates were higher in the TGF-β1+melatonin,TGF-β1+melatonin+siDCN,and TGF-β1+DCN groups than the TGF-β1 group(P＜0.05).The cell sur-vival rate was higher for the TGF-β1+melatonin group than the TGF-β1+melatonin+siDCN group(P＜0.05).Western blotting and real-time PCR showed DCN and that E-cadherin were significantly down-regulated in the TGF-β1 group compared with the control group(P＜0.05).Compared with the TGF-β1 group,the TGF-β1+melatonin and TGF-β1+melatonin+siDCN groups showed up-regulated E-cadherin and DCN expression levels and down-regulated TGF-β1 and Smad2 expression levels(P＜0.05).Compared with the TGF-β1+melato-nin+siDCN group,the TGF-β1+melatonin+siDCN group showed up-regulated E-cadherin and DCN expression levels and down-regulated TGF-β1 and Smad2 expression levels(P＜0.05).Conclusion Melatonin can delay the EMT of human peritoneal mesoepithelial cells,and the DCNgene may be an important target to inhibit the EMT of these cells.

Objective To analyse the concept of subjective financial distress in cancer patients.Methods Papers in regarding the subjective financial distress were retrieved from the databases such as China National Knowledge Infrastructure(CNKI),Wangfang Database,PubMed,Cochrane Library,Web of Science,CINAHL,and Embase from the inceptions to 16th October,2022.Walker and Avant's concept analysis was performed to analyse the acquired articles.Results A total of 48 articles were retrieved and included in the study.Walker and Avant's concept analysis showed that the subjective financial distress in the patients was subject to the 3 defining attributes:perceived economic risk,coping behaviours,and negative emotional reactions.The antecedents of this distress included individual factors,disease and treatment factors,and social factors.The consequences of them were the increase in negative health behaviours and poorer quality of life.Conclusions The attributes,antecedents and consequences of subjective financial distress,as identified through the conceptual analysis,can serve as a reference for subsequent researches.In future studies,it would be beneficial by further exploring the connotation by considering China's healthcare system.

Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.

Objective To determine the optimal conditions for CXCR4 upregulation by comparing the expression levels of chemokine(C-X-C motif)receptor 4(CXCR4)in MSCs cultured with varying concentrations of oxygen and hydrogen peroxide(H2O2).Methods MSCs were cultured with 0.1％,1％,or 3％O2 and 50 μmol/L H2O2 for different lengths of time(3,6,12,and 24 h).The mRNA and protein expressions of CXCR4 in MSCs were measured by real-time quantitative PCR(qPCR),Western blotting,and immunofluorescence staining.The viability and chemotactic ability of MSCs were measured using CCK-8,wound-healing and Transwell migration assays.Results Both hypoxia and H2O2 treatment were found to upregulate MSC expressions of CXCR4 to some extent.The mRNA and protein levels of CXCR4 were higher after 6-12 h of culture of MSCs with 3％O2,and significantly higher when treated with H2O2 for 6 h.Cell viability was significantly increased after culture with 3％O2 compared with the control group and both 3％O2 and H2O2 pretreatment could enhance chemotactic migration in MSCs.Conclusion Culture with 3％O2 and H2O2 pretreatment can upregulate CXCR4 expressions in MSCs and enhance migration in cells,with superior effects observed with 3％O2.Therefore,treatment with 3％O2 represents the best choice for upregulating the chemotactic ability of MSCs.