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.

Glioma is the most common primary central nervous system tumor,mainly derived from glial cells,with strong invasiveness,easy recurrence,and poor prognosis.Glioblastoma is a high-grade glioma with the highest degree of malignancy.The clinical treatment method is mainly surgical resection,supplemented by compre-hensive treatment such as radiotherapy,chemotherapy,and electric field therapy,but the treatment effect is not satisfactory.In recent years,with the rapid development of the field of tumor immunotherapy,CD73 is a novel immune checkpoint related to adenosine metabolism,which can promote tumor progression by inhibiting anti-tumor immune responses and promoting angiogenesis.This article systematically reviews the mechanism of action of CD73 and discusses its biological role and application in glioma,aiming to provide potential treatment options for glioma patients.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Objective:To investigate the effect of mucosal thickness around implants on marginal bone resorption.Methods:A retrospective analysis was conducted on the clinical data of 75 patients who received single-tooth implant restorations at Shaoxing Stomatological Hospital from December 2020 to May 2022. The patients were divided into two groups based on mucosal thickness: the thin gingiva group ( n = 40) and the thick gingiva group ( n = 35). In the thin gingiva group, implants were placed 1.5 mm below the bone surface, while in the thick gingiva group, implants were placed at the bone surface. Implant survival rates, marginal bone resorption, bone remodeling, and the incidence of adverse reactions were compared between the two groups. Results:The implant survival rate in the thin gingiva group was significantly lower than that in the thick gingiva group [75.00% (30/40) vs. 94.29% (33/35), χ 2 = 5.17, P < 0.05]. After 9 months of weight bearing, marginal bone resorption value in the thin gingiva group was significantly higher than that in the thick gingiva group [(0.16 ± 0.04) vs. (0.14 ± 0.02), t = 2.83, P < 0.05]. The bone remodeling value in the thin gingiva group was significantly lower than that in the thick gingiva group [(1.03 ± 0.21) vs. (1.25 ± 0.34), t = 3.48, P < 0.05]. The incidence of adverse reactions including infection, bleeding, occlusal weakness, and pain in the thin gingiva group was significantly higher than that in the thick gingiva group [25.00% (10/40) vs. 5.72% (2/35), χ 2 = 5.17, P < 0.05]. Conclusion:A mucosal thickness of ≥ 3 mm is associated with a higher survival rate of implants placed below the bone surface, which better maintains bone tissue stability, reduces bone resorption, promotes bone remodeling, and decreases the incidence of adverse reactions.

BACKGROUND: 3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction. METHODS: In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes’ effect of promotion vaginal reconstruction and to explore the mechanism in this process. RESULTS: It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway. CONCLUSION The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.

OBJECTIVE To construct the evaluation index system for scientific research ability of hospital pharmacists， and provide reference for the improvement of hospital pharmacists’ scientific research ability and the formulation of relevant scientific research policies. METHODS The relevant indexes of scientific research evaluation of hospital pharmacists were extracted by literature analysis， and consultation questionnaire was designed according to Likert grade 5 scoring method. Delphi method was used to conduct two rounds of questionnaire consultation for 28 experts， and the weight of each index was determined by analytic hierarchy process. The reliability and validity of index system were analyzed by questionnaire survey. RESULTS After two rounds of expert correspondence， evaluation index system for scientific research ability of hospital pharmacists was finally determined from three core dimensions： basic scientific research ability， scientific research achievements and transformation ability， academic influence and personnel training （including 11 sub-dimensions and 34 measurement items）. The weight value of each dimension index was determined. The result of reliability and validity analysis confirmed the scientific rationality of the index system. CONCLUSIONS The established evaluation index system for scientific research ability of hospital pharmacists is innovative， comprehensive and scientific. The index system model can provide reference for the improvement of hospital pharmacists’ scientific research ability and the formulation of relevant scientific research policies.

Objective:To investigate the effect of hsa-miR-199a-5p on keloid fibroblasts (KFs) fibrosis and its relationship with TGF-β/Smad signaling pathway in vitro. Methods:KFs were infected with the lentiviral vector carrying hsa-miR-199a-5p (hsa-miR-199a-5p group) or the blank vector (rLv-NC group), and a blank control group was set. The proliferation status of KFs were detected by CCK-8 assay. At 48 hours after infection, the expression of hsa-miR-199a-5p in KFs were detected by quantitative real-time PCR (qRT-PCR); cell apoptosis was detected by flow cytometry analysis; cell invasion ability was detected by Transwell; The mRNA and protein levels of collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin(α-SMA), Smad3 and TGF-β1 were detected by qRT-PCR and Western blotting, respectively.Results:At 48 hours after infection with RLV-hsa-miR-199a-5p lentiviral vector, the mRNA expression level of hsa-miR-199a-5p in hsa-miR-199a-5p group KFs was significantly higher than that in rLv-NC group and blank control group, and the difference was statistically significant ( P<0.01). Compared with the rLv-NC and blank control groups, the proliferation rate and invasiveness of the hsa-miR-199a-5p group decreased, the apoptosis rate increased, with statistical significance ( P<0.01); the mRNA and protein expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, Smad3 and TGF-β1 in hsa-miR-199a-5p group were significantly lower than those in rLv-NC group and blank control group, with statistical significance ( P<0.01). Conclusions:hsa-miR-199a-5p may inhibit the proliferation and invasion of KFs by inhibiting TGF-β/Smad pathway, and promote the apoptosis of KFs, thus inhibiting keloid fibrosis.

Objective:To investigate the effect of hsa-miR-199a-5p on keloid fibroblasts (KFs) fibrosis and its relationship with TGF-β/Smad signaling pathway in vitro. Methods:KFs were infected with the lentiviral vector carrying hsa-miR-199a-5p (hsa-miR-199a-5p group) or the blank vector (rLv-NC group), and a blank control group was set. The proliferation status of KFs were detected by CCK-8 assay. At 48 hours after infection, the expression of hsa-miR-199a-5p in KFs were detected by quantitative real-time PCR (qRT-PCR); cell apoptosis was detected by flow cytometry analysis; cell invasion ability was detected by Transwell; The mRNA and protein levels of collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin(α-SMA), Smad3 and TGF-β1 were detected by qRT-PCR and Western blotting, respectively.Results:At 48 hours after infection with RLV-hsa-miR-199a-5p lentiviral vector, the mRNA expression level of hsa-miR-199a-5p in hsa-miR-199a-5p group KFs was significantly higher than that in rLv-NC group and blank control group, and the difference was statistically significant ( P<0.01). Compared with the rLv-NC and blank control groups, the proliferation rate and invasiveness of the hsa-miR-199a-5p group decreased, the apoptosis rate increased, with statistical significance ( P<0.01); the mRNA and protein expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, Smad3 and TGF-β1 in hsa-miR-199a-5p group were significantly lower than those in rLv-NC group and blank control group, with statistical significance ( P<0.01). Conclusions:hsa-miR-199a-5p may inhibit the proliferation and invasion of KFs by inhibiting TGF-β/Smad pathway, and promote the apoptosis of KFs, thus inhibiting keloid fibrosis.

Objective:To evaluate the relationship between silent information regulator 2 homologue 3 (SIRT3) and mitochondrial function in mice with endotoxin-induced lung injury.Methods:Twenty clean-grade healthy adult male wild C57BL/6 (SIRT3 + /+ ) mice, 20 SIRT3 knockout (SIRT3 -/-) mice, weighing 20-25 g, aged 6-8 weeks, were studied.SIRT3 + /+ mice and SIRT3 -/- mice were divided into 4 groups ( n=5 each) according to the random number table method: blank control group (group C, group SIRT3 -/-C), endotoxin-induced lung injury group (group L, group SIRT3 -/-L), endotoxin-induced lung injury plus resveratrol group (group L+ R, group SIRT3 -/-L+ R), and resveratrol group (group R, group SIRT3 -/-R). Resveratrol 15 mg/kg was intraperitoneally injected once a day for 7 consecutive days in L+ R, R, SIRT3 -/-L+ R and SIRT3 -/-R groups, while the equal volume of normal saline was injected in the rest groups.Lipopolysaccharid 15 mg/kg was injected via the tail vein to develop a mouse model of endotoxin-induced lung injury at 30 min after resveratrol injection on 7th day, in L+ R and SIRT3 -/-L+ R groups and at the corresponding time points in L and SIRT3 -/-L groups, while the equal volume of normal saline was injected in the other groups.Blood samples were collected from the orbital venous plexus at 12 h after injection of normal saline or lipopolysaccharid for determination of serum total oxidation state (TOS) and total antioxidant state (TAS) levels by the xylenol orange method and ABTS colorimetric method, and the oxidative stress index (OSI) was calculated.After the mice were sacrificed, the lung tissues were taken for microscopic examination of the pathological changes which were scored and for determination of the mitochondrial membrane potential (MMP) (by JC-1 method), cellular oxygen consumption rate (OCR) (by the specific fluorescent probe method), and expression of SIRT3 (by Western blot). Results:Compared with group C or group SIRT3 -/-C, the lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in L, L+ R, SIRT3 -/-L and SIRT3 -/-L+ R groups ( P<0.05). Compared with group L, the lung injury score, serum TOS concentration and OSI were significantly decreased, TAS concentration, MMP and OCR were increased, and SIRT3 expression was up-regulated in group L+ R, and lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in group SIRT3 -/-L ( P<0.05). Compared with group L+ R, the lung injury score, serum TOS concentration and OSI were significantly increased, the TAS concentration, MMP and OCR were decreased, and the expression of SIRT3 was down-regulated in group SIRT3 -/- L+ R ( P<0.05). There was no significant difference in the indicators mentioned above between group SIRT3 -/-L+ R and group SIRT3 -/-L ( P>0.05). Conclusions:Down-regulation of SIRT3 expression can lead to impaired mitochondrial function, which is involved in the pathophysiological mechanism of endotoxin-induced lung injury.

Objective:To investigate status quo of professional self-identity of newly recruited nurses and analyze its influencing factors.Methods:From July to December 2018, a two-stage cluster sampling method was adopted. In the first stage, according to the economic and administrative regions, the area was divided into six regions, namely Northeast China, East China, North China, South China, Southwest China and Northwest China, and one ClassⅢGrade A hospital was randomly selected from each administrative region. In phase 2, a cluster sampling was used to select newly recruited nurses from 6 sample hospitals in 2018. A questionnaire survey was conducted using the Nurses' Professional Self-identity Scale. A total of 267 questionnaires were collected, 258 of which were valid, with an effective recovery rate of 96.63%.Results:The total mean score of Nurses' Professional Self-identity Scale for 258 newly recruited nurses was (3.84±0.66) . Univariate analysis showed that there were statistically significant differences in the total mean score of Nurses' Professional Self-identity Scale of newly recruited nurses with different ages, internship time, education background and labor and personnel relations. Multiple linear regression analysis found that educational background, internship time, labor and personnel relations were the influencing factors of the professional self-identity of newly recruited nurses.Conclusions:The professional self-identity of newly recruited nurses is at a medium level. Equal pay for equal work is one of the important guarantees to improve the professional self-identity of newly recruited nurses. Nursing managers should pay attention to the work pressure of new nurses with high academic qualifications and adopt targeted training programs to improve the professional identity of new nurses and ensure the stable development of the nursing team in my country.