To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Posterior capsule opacification(PCO)is a common postoperative complication of cataract surgery, primarily caused by the proliferation and migration of residual lens epithelial cells(LECs). Although neodymium-doped yttrium aluminum garnet(Nd:YAG)laser posterior capsulotomy effectively treats PCO, it carries risks of complications such as cystoid macular edema(CME). Thus, preventing PCO formation is of critical clinical importance. Despite advancements in intraocular lens(IOL)materials and designs, achieving complete PCO eradication remains challenging. This review systematically examines recent advancements in surface-modified IOLs, including anti-biofouling IOL(reducing LECs adhesion), capsular adhesion-enhanced IOL(promoting capsular bag integration), micro-patterned IOL(physically inhibiting migration), photothermal/photodynamic IOL(inducing light-activated LECs apoptosis), and drug-eluting IOL(sustained drug release). These surface modification strategies demonstrate synergistic effects through complementary mechanisms(including physical barrier formation, chemical intervention, and bioactive regulation), effectively suppressing LECs proliferation while significantly reducing PCO incidence. Importantly, these approaches eliminate the risks associated with conventional Nd:YAG laser treatment, offering substantial advantages. By providing a comprehensive evaluation of these cutting-edge technologies, this review serves as a valuable reference for IOL design optimization. It represents a paradigm shift in cataract management strategies, transitioning from reactive therapeutic interventions to proactive preventive measures, and ultimately leads to improving long-term visual outcomes for patients.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

One of the key components of adsorbents for blood purification is the microsphere adsorbent. Microsphere adsorbents should meet the following requirements: stable physical and chemical structures, easy for functional modification to endow the adsorbents with specific adsorption functions or characteristics, with good biocompatibility and with low non-specific adsorption, as well as with enough mechanical strength. Microsphere adsorbents prepared from polysaccharide bio-based materials fulfill the above requirements and have been widely used in the field of blood adsorption. In this article, adsorbents prepared from polysaccharide bio-based materials such as cellulose, agarose, alginate, as well as adsorbents prepared from the aforementioned materials and carbon materials and the application of the said bio-based adsorbents in blood adsorption is reviewed. The future development is also discussed, aiming to provide guidance and reference for the preparation, functional modification and application research of bio-based adsorbents for blood adsorption.
Microspheres ; Adsorption ; Humans

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective:To investigate the effects of gambogenic acid(GNA)on the proliferation and apoptosis of CAL27 cell xenograft tumor in nude mice.Methods:18 SPF nude mice were randomly divided into 3 groups(n=6).All nude mice were inoculated with CAL27 cells at logarithmic growth stage to establish subcutaneous transplanted tumor models.The mice in low and high dose GNA groups were treated with GNA of 8.0 mg/kg iv.and 16.0 mg/kg iv.every other day,respectively,and those in the control group was given the same amount of normal saline.The tumor growth curve was plotted during drug administration.2 weeks later,the nude mice were sacrificed,the tumor tissue was removed and the tumor inhibition rate was evaluated by the tumor size measurements.TUNEL as-say was used to detect the apoptosis of transplanted tumor cells in the groups.The expression levels of AKT,Bcl-2 and PI3K proteins in tumor tissue were detected by immunohistochemistry(IHC).The toxicity and side effects of GNA on normal tissues were detected by HE staining.Results:The transplanted tumors in low and high dose GNA groups grew slowly,and the tumor weight and volume were significantly lower than those in the control group(P＜0.05),the tumor inhibition ratio of low and high dose groups was 57.58％and 83.68％respectively.TUNEL results showed that the apoptosis index of GNA low and high dose groups was higher that of control group(P＜0.05).IHC results showed that the expression of AKT,Bcl-2 and PI3K in the tumor tissues of nude mice in low and high dose GNA groups was lower than that in the control group(P＜0.05).HE results showed that GNA had not effect on normal tissues and or-gans(P＜0.05);Conclusion:GNA may induce CAL27 cell apoptosis by regulating the expression of AKT,Bcl-2 and PI3K,and in-hibites the development of human tongue squamous cell carcinoma with little effect on normal tissues and organs.