AIM: To analyze changes in the anterior chamber angle structure in patients with implantable collamer lens with central-port(ICL V4c)implantation, and to investigate their associations with preoperative anterior segment anatomical parameters.METHODS: Retrospective case study. Patients with myopia or myopia combined with astigmatism who underwent ICL V4c implantation in the Refractive Surgery Center of the Department of Ophthalmology, the 2nd Affiliated Hospital of Harbin Medical University between July 2024 and November 2024 were recruited. Preoperative and postoperative uncorrected visual acuity, best-corrected visual acuity, intraocular pressure, anterior chamber angle(ACA), white-to-white distance(WTW), anterior chamber depth(ACD), angle to angle distance(ATA), horizontal sulcus-to-sulcus distance(HSTS), vertical sulcus-to-sulcus distance(VSTS),crystalline lens rise(CLR), pupil diameter(PD), iris thickness at 750 μm from the scleral spur(IT750),maximal iris thickness(ITM), iris curvature(I-Curv), and iris cross-sectional area(I-Area), angle opening distance(AOD750), thetrabecular-iris angle(TIA750)and the trabecular-iris space area(TISA750)in the temporal, nasal, superior, and inferior directions,as well as the vault at various postoperative time points were measured.RESULTS: The study involved 40 patients(79 eyes)with myopia or myopia combined with astigmatism who underwent ICL V4c implantation(10 males and 30 females)with the mean age of 24.73±3.79 y. Compared with preoperative measurements, at 1 mo postoperatively, the AOD750, TIA750, and TISA750 parameters at the four angles(temporal, nasal, superior, and inferior)all showed a significant reduction(P<0.01). Statistically significant differences in vault were observed at postoperative 1d(0.49±0.1), postoperative 1 wk(0.43±0.14), and postoperative 1 mo(0.41±0.14)(all P<0.001). Correlation analysis indicated that the postoperative state of the anterior chamber angle was jointly influenced by anterior chamber parameters(ACD, ATA, HSTS、VSTS), iris morphology(I-Area, IT750), pupil size(PD), and surgical factors(ICL size, early vault), and that the combination of influencing factors varied across different orientations. Regression analysis showed that ACD was positively correlated with all postoperative anterior chamber angle parameters(P<0.05). IT750 exhibited negative correlations with the temporal and inferior angles(P<0.05). I-Area was positively correlated with temporal AOD750 and TISA750(P<0.05), and PD had negative correlations with temporal TIA750 and nasal AOD750(P<0.05).CONCLUSION: Postoperative anterior chamber angle narrowing is a common phenomenon after ICL V4c implantation. The degree of change exhibits a significant correlation with multiple preoperative anterior segment anatomical parameters. Preoperative comprehensive assessment of ACD, PD, and IT750 may facilitate the evaluation of the risk of postoperative angle changes and the enhancement of surgical safety.

OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.

Objective: This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China. Methods: In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms. Results: In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001). Conclusion Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric cancer and its effect on gastric cancer progression and prognosis were analyzed using publicly available databases and clinical data of patients undergoing radical surgery in our hospital, and its possible biological functions were explored using KEGG and GO analyses. In gastric cancer HGC-27 cells, the effects of lentivirus-mediated TMCO1 overexpression and TMCO1 silencing on cell apoptosis, proliferation, invasion and migration were examined. RESULTS: TMCO1 expression was significantly elevated in gastric cancer tissues (P<0.05), and its high expression was positively correlated with cancer progression (P<0.001) and a lowered postoperative 5-year survival rate of the patients (P<0.05). Bioinformatic analyses suggested that TMCO1 may affect gastric cancer cell apoptosis via Wnt signaling. In HGC-27 cells, TMCO1 overexpression significantly promoted tumor cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion, whereas TMCO1 silencing produced the opposite effects. Western blotting showed that β-catenin levels were significantly upregulated in TMCO1-overexpressing cells and downregulated in cells with TMCO1 silencing. CONCLUSIONS TMCO1 is overexpressed in gastric cancer tissues, and its high expression promotes gastric cancer progression and affects long-term prognosis of the patients possibly by activating the Wnt/ β-catenin signaling pathway to inhibit apoptosis of gastric cancer cells.
Humans ; Stomach Neoplasms/metabolism* ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Gene Expression Regulation, Neoplastic

Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
Animals ; Neuralgia/pathology* ; Septal Nuclei/physiopathology* ; Male ; Spleen/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Mice, Inbred C57BL ; Splenectomy ; Mice ; Neural Pathways/physiopathology* ; Disease Models, Animal ; Ganglia, Spinal/physiopathology* ; Sympathectomy ; Macrophages

Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis (LN), and targeting plasma cell aggregation offers a promising therapeutic strategy. Ginsenoside compound K (i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol) (CK), a derivative of ginsenoside, has indicated significant potential in alleviating renal damage in lupus-prone mice, potentially by modulating B cell dynamics in response to endoplasmic reticulum (ER) stress. In this study, CK (20 or 40 mg/kg) was orally administered to female MRL/lpr mice for 10 weeks. The effects of CK on B cell subpopulations, renal function, and histopathological changes were evaluated. Single-cell ribonucleic acid sequencing was employed to analyze gene expression profile and pseudotime trajectories during B cell-mediated renal injury. Additionally, in vitro B cell assays were conducted to explore the role of the sirtuin-1 (SIRT1)-X-box binding protein 1 (XBP1) axis in ER stress. Our findings demonstrated that CK effectively reduced anti-double stranded DNA (dsDNA) antibody levels, alleviated systemic inflammation, improved renal function, and facilitated the clearance of deposited immune complexes. CK likely suppressed the unfolded protein response (UPR), delaying the differentiation of renal-activated B cells into plasma cells. It promoted B cell-specific SIRT1 activation and inhibited the splicing of XBP1 into its active form, XBP1s. CK also restored ER morphology by interacting with calmodulin (CALM) to maintain ER calcium storage, reinforcing SIRT1 functional integrity and promoting XBP1 deacetylation, thereby limiting plasma cell differentiation. In conclusion, CK mitigates plasma cell accumulation in the renal microenvironment by preventing SIRT1-mediated XBP1 splicing, offering a potential therapeutic approach for LN.