AIM: To observe the characteristics of best corrected visual acuity(BCVA), microperimetry(MP), multifocal electroretinogram(mfERG), and optical coherence tomography angiography(OCTA)parameters in patients with idiopathic epiretinal membrane(IERM), and conduct a comparative study and correlation analysis on these parameters.METHODS:This was a cross-sectional study. A total of 56 patients(56 eyes)diagnosed with IERM who visited our hospital between February 2021 and November 2024 were collected as IERM group, and 33 healthy individuals(33 eyes)undergoing physical examinations were included as control group. Parameters were compared between the IERM group and the control group, as well as among IERM subgroups at different stages. Additionally, correlations among visual function parameters and between these visual function parameters and vascular structural OCTA parameters were analyzed.RESULTS: The general data of patients in the control group and IERM group were comparable. In the IERM group, BCVA, retinal sensitivity(RS), P1 wave amplitude in ring 1, superficial capillary plexus parafoveal vessel density(SCPpfvd), deep capillary plexus parafoveal vessel density(DCPpfvd), and the foveal avascular zone(FAZ)area were significantly lower than the control group(all P<0.01). In contrast, central retinal thickness(CRT), superficial capillary plexus foveal vessel density(SCPfvd), and deep capillary plexus foveal vessel density(DCPfvd)were significantly increased(all P<0.001). When comparing different stages of IERM, significant differences were observed in BCVA, CRT, RS, SCPfvd, and FAZ(all P<0.01). In eyes affected by IERM, BCVA(LogMAR)was negatively correlated with RS; P1 wave amplitude in ring 1 positively correlated with P1 wave implicit time in ring 1; SCPfvd positively correlated with BCVA(LogMAR)and negatively correlated with RS; DCPfvd negatively correlated with P1 wave implicit time in ring 1; and DCPpfvd positively correlated with RS(all P<0.05).CONCLUSION: Eyes with IERM exhibit abnormalities in visual function parameters and vascular structure, with varying degrees of alteration in BCVA, CRT, RS, SCPfvd, and FAZ across different stages. Comprehensive evaluation of BCVA, MP, mfERG, and OCTA contributes to a deeper understanding of the nature of IERM and aids in formulating appropriate diagnosis and treatment plans.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

Objective To investigate the effect of Mysm1 on the differentiation of neural stem cells(NSCs)into astrocytes and the possible mechanism.Methods NSCs were prepared from E12.5 cortices of wild-type C57BL/6 mice,cultured in vitro and induced to differentiate into astrocytes.Immunofluorescence staining,real-time quantitative PCR and Western blot assay were used to detect the expressions of Mysm1 during the differentiation of NSCs into astrocytes in vitro.Lentivirus was used to knock down Mysm1 expressions in NSCs before real-time quantitative PCR and Western blot assay were used to detect the knockdown efficiency.Immunofluorescence staining and Western blot assay were used to compare the differentiation of NSCs into astrocytes before and after Mysm1 knockdown in vitro.Transcriptomics was adopted to detect the differential gene after knockdown of Mysm1 in NSCs in vitro.Western blot assay was used to verify the changes of proteins associated with the differential gene.Cut-Tag was used to detect the enrichment of Mysm1 in the promoter region of glial fibrillary acidic protein(GFAP)genes during the differentiation of NSCs into astrocytes in vitro.After overexpression of GFAP following knockdown of Mysm1,immunofluorescence staining and Western blot assay were used to compare the differentiation of NSCs into astrocytes before and after overexpression in vitro.Results The expression of Mysm1 was gradually increased when NSCs were induced to differentiate into astrocytes in vitro.Mysm1 knockdown inhibited the differentiation of NSCs into astrocytes in vitro.Mysm1 affected the differentiation of NSCs into astrocytes by regulating the expression of GFAP.Overexpression of GFAP after Mysm1 knockdown partially rescued the ability of NSCs to differentiate into astrocytes.Conclusion Mysm1 regulates the differentiation of NSCs into astrocytes by epigenetically controlling GFAP transcription.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Objective:To search and summarize the best evidence for preoperative prehabilitation in patients with lung cancer complicated by chronic obstructive pulmonary disease and to inform the management of preoperative prehabilitation in patients with lung cancer combined with COPD by clinical providers.Methods:Systematically guideline websites, professional society websites, evidence-based databases, and comprehensive databases were searched for types of literature including clinical decision making, guidelines, expert consensus, evidence summaries, systematic evaluations, Meta-analyses, and randomized controlled trials. The time for the retrieval was from the inception of databases until October 31th, 2023. And the quality of the included literature was evaluated and evidence was extracted, evaluated the quality of the included literature, and extracted evidence.Results:Finally, 18 articles were included, including 8 guidelines, 8 expert consensus, and 2 systematic reviews. Summarized the 30 best evidence in 4 areas of prerehabilitation: need, timing, location, content (including smoking cessation management, respiratory exercise, exercise, nutritional support, and medication management).Conclusions:This study summarizes the best evidence for preoperative prehabilitation in patients with lung cancer combined with chronic obstructive pulmonary disease, and healthcare professionals should be mindful of the need to develop preoperative prehabilitation protocols judiciously, taking into account the specific clinical context during the subsequent translation of the evidence to the clinic.

Objective Ionization chamber detector is commonly used for direct and continuous measurement of tritium concentration in the air. However, the measurement sensitivity is low due to the limitations of weak current measurement technology. It is necessary to develop a proportional counter for measuring tritium in the air. Methods This study involved the design of a proportional counter, considering various factors such as materials and structure. The stability, plateau curve, detection efficiency, and energy spectrum of the counter were tested. Results The coefficient of variation of the proportional counter was 3.14%, which met the standard requirement of being less than 15%. The plateau length was 260 V and the plateau slope was 0.80%/100V, which met the requirement of being less than 1%/100V. The tritium detection efficiency reached 68.02%. The energy spectrum measurement indicated a significant difference between tritium signal generated by the proportional counter and background signal, and the distribution of tritium in the energy spectrum was more concentrated. The background counting rate during tritium gas activity measurement could be reduced through energy spectrum measurement. Conclusion The proportional counter can provide a reference for the direct and continuous measurement of tritium in the air.

Objective:To observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR).Methods:A cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. Results:A total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups ( H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio ( OR)=1.440, 95% confidence interval ( CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [ OR=1.990, 95% CI 1.440-2.749, P<0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95% CI 0.706-0.796, P<0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. Conclusions:The NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.

Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate,posing a serious threat to human health.Sodium-glucose linked transporter 2(SGLT2)inhibitors are a new type of oral hypoglycemic drug.SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion,but also by improving islet β cell function,reducing inflammatory responses,and inhibiting oxidative stress.In addition,SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism;reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function.They can also improve blood lipids by increasing degradation of triacylglycerol;reduce blood uric acid by promoting uric acid excretion in kidney and intestine,and by reducing uric acid synthesis.This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.