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.

Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a⁺ and CD207⁺ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans ; Bone Diseases/therapy* ; Histiocytosis, Langerhans-Cell/therapy*

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Objective To observe the clinical efficacy of acupuncture at Neiyingxiang(EX-HN09)points combined with western medicine in the treatment of allergic rhinitis of deficiency-cold of lung qi type.Methods Sixty patients with deficiency-cold of lung qi type of allergic rhinitis were randomly divided into observation group and control group,with 30 patients in each group.The control group was treated with Desloratadine Tablets combined with Mometasone Furoate Aqueous Nasal Spray,and the observation group was treated with acupuncture at Neiyingxiang points combined with the self-made rhinitis recipe on the basis of the control group,and the clinical efficacy of the two groups was evaluated after 14 days.The changes of nasal symptom scores,Visual Analogue Scale(VAS)and rhinoconjunctivitis quality of life scores of the patients of the two groups were observed before and after the treatment.After 14 days of treatment,the clinical efficacy of the two groups was evaluated.The changes in nasal symptom scores,as well as VAS and rhinoconjunctivitis quality of life questionnaire(RQLQ)scores were observed before and after treatment.The changes in traditional Chinese medicine(TCM)sydnrome scores and serum immunoglobulin E(IgE)were compared before and after treatment in the two groups,and the safety of the two groups was evaluated.Results(1)The total effective rate of the observation group was 93.33%(28/30),and the control group was 73.33%(22/30).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the symptoms of nasal congestion,sneezing,runny nose and nasal itching were significantly improved in the two groups(P＜0.01),and the observation group was significantly superior to the control group in improving nasal symptoms,and the differences were statistically significant(P＜0.05).(3)After treatment,the VAS scores of patients in the two groups were significantly improved(P＜0.01),and the observation group was superior to the control group in improving VAS scores,with statistically significant differences(P＜0.05).(4)After treatment,the PQLQ scores of patients in the two groups improved significantly(P＜0.01),and the observation group was significantly superior to the control group in improving the PQLQ scores,and the difference was statistically significant(P＜0.05).(5)After treatment,the TCM syndrome scores of the patients in the two groups were significantly improved(P＜0.01),and the observation group was significantly superior to the control group in improving TCM syndrome scores,with statistically significant differences(P＜0.05).(6)After treatment,the serum IgE levels of patients in the two groups were significantly improved(P＜0.01),and the observation group was significantly superior to the control group in improving serum IgE levels(P＜0.05),with a statistically significant difference.(7)There was no significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Acupuncture at Neiyingxiang points plus self-made rhinitis recipe combined with western medicine in the treatment of deficiency-cold of lung qi type of allergic rhinitis can significantly improve the clinical symptoms of the patients,thus improving the quality of life of the patients,and the therapeutic efficacy is remarkable.

Objective·To evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.