AIM:To compare and analyze the effectiveness and safety of reducing the diameter of the back optical zone diameter(BOZD)of orthokeratology lens designed by CRT and VST in controlling the progression of myopia in children and adolescents.METHODS:Retrospective study. The study subjects were 400 myopia patients aged 8-16 years who were admitted to the orthokeratology fitting center of our hospital from June 2019 to May 2022, with 400 eyes(including right eye data analysis). The subjects were divided into CRT-S group(BOZD<6.0 mm), CRT group(BOZD=6.0 mm), VST-S group(BOZD<6.2 mm), VST group(BOZD=6.2 mm)according to the brand of orthokeratology lens and BOZD group, with 100 cases in each group. Uncorrected visual acuity(UCVA), corneal flat K value, axial length, spherical equivalent, and incidence of corneal injury were collected and analyzed at 1 d, 1 wk, 1 and 6 mo, 1 and 2 a, respectively.RESULTS:After wearing lenses for 1 d, the UCVA of the VST-S group improved the fastest, but after 1 wk, all groups reached a good UCVA, and there was no significant difference between groups. The corneal flat K value of the CRT-S group decreased the most after wearing lenses for 6 mo, and there was no significant difference in the corneal flat K value of all groups after 1 year of lens wearing. At each time point, the axial length growth decreased significantly after reducing the BOZD of the same brand of orthokeratology lens. At 6 mo, there was no significant difference in the axial length growth and defocus ring diameter between the CRT-S group and the VST-S group, but at 1 and 2 a, the VST-S group had significantly lower axial length growth and defocus ring diameter than the CRT-S group. The growth of the diopter sphere and spherical equivalent(SE)was significantly reduced when the BOZD of the same brand of orthokeratology lens was reduced at 2 a follow-up. The VST-S group had the smallest changes in the degree of SE and had the best myopia control effect. There was no significant difference in the change value of the diopter cylinder and the incidence of corneal injury among the four groups.CONCLUSION:Reducing the BOZD of the orthokeratology lens can effectively control the growth of the axial length and the progression of myopia degree. The myopia control effect of the VST lens is better than that of the CRT lens after reducing the BOZD. Reducing the BOZD of the orthokeratology lens does not increase the risk of additional corneal injury.

AIM:To compare and analyze the effectiveness and safety of reducing the diameter of the back optical zone diameter(BOZD)of orthokeratology lens designed by CRT and VST in controlling the progression of myopia in children and adolescents.METHODS:Retrospective study. The study subjects were 400 myopia patients aged 8-16 years who were admitted to the orthokeratology fitting center of our hospital from June 2019 to May 2022, with 400 eyes(including right eye data analysis). The subjects were divided into CRT-S group(BOZD<6.0 mm), CRT group(BOZD=6.0 mm), VST-S group(BOZD<6.2 mm), VST group(BOZD=6.2 mm)according to the brand of orthokeratology lens and BOZD group, with 100 cases in each group. Uncorrected visual acuity(UCVA), corneal flat K value, axial length, spherical equivalent, and incidence of corneal injury were collected and analyzed at 1 d, 1 wk, 1 and 6 mo, 1 and 2 a, respectively.RESULTS:After wearing lenses for 1 d, the UCVA of the VST-S group improved the fastest, but after 1 wk, all groups reached a good UCVA, and there was no significant difference between groups. The corneal flat K value of the CRT-S group decreased the most after wearing lenses for 6 mo, and there was no significant difference in the corneal flat K value of all groups after 1 year of lens wearing. At each time point, the axial length growth decreased significantly after reducing the BOZD of the same brand of orthokeratology lens. At 6 mo, there was no significant difference in the axial length growth and defocus ring diameter between the CRT-S group and the VST-S group, but at 1 and 2 a, the VST-S group had significantly lower axial length growth and defocus ring diameter than the CRT-S group. The growth of the diopter sphere and spherical equivalent(SE)was significantly reduced when the BOZD of the same brand of orthokeratology lens was reduced at 2 a follow-up. The VST-S group had the smallest changes in the degree of SE and had the best myopia control effect. There was no significant difference in the change value of the diopter cylinder and the incidence of corneal injury among the four groups.CONCLUSION:Reducing the BOZD of the orthokeratology lens can effectively control the growth of the axial length and the progression of myopia degree. The myopia control effect of the VST lens is better than that of the CRT lens after reducing the BOZD. Reducing the BOZD of the orthokeratology lens does not increase the risk of additional corneal injury.

Retinal vein occlusion(RVO)is the second most common blinding retinal vascular disease, and its secondary macular edema(ME)is an important cause of visual function impairment in patients. Intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs serves as the first-line treatment, yet it is confronted with such issues as the need for repeated injections and non-response in some patients. Imaging and laboratory biomarkers play a crucial role in the early accurate diagnosis, prediction of disease progression, and evaluation of visual prognosis of RVO-ME. This study systematically reviews the research progress of imaging and laboratory biomarkers related to the prognosis of RVO-ME after anti-VEGF treatment in recent years, covering imaging biomarkers like central retinal thickness and ellipsoid zone integrity, as well as laboratory biomarkers such as serum APLN and aqueous humor IL-6. It summarizes the associations between different biomarkers and the prognosis of anti-VEGF therapy, aiming to provide a basis for the early accurate assessment and optimization of individualized treatment for RVO-ME patients, which holds significant clinical reference value.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.