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.

AIM: To evaluate the efficacy of 0.01% hypochlorous acid as a conjunctival sac disinfectant before cataract phacoemulsification and its impact on the ocular surface.METHODS: Randomized controlled clinical trial. A total of 285 patients who were scheduled for cataract phacoemulsification surgery were randomly divided into the hypochlorous acid group and the povidone iodine group. Before and after disinfection, conjunctival sac swabs were taken, and bacterial culture and colony-forming units(CFUs)testing were performed using blood agar and chocolate agar media, respectively. All patients were evaluated for ocular symptom scores and pain severity scores 2 h, 1 d, and 1 wk after disinfection, and underwent corneal fluorescein staining, eye redness index, tear meniscus height, and noninvasive breakup time(NIBUT)examination. The incidence of endophthalmitis after surgery was recorded.RESULTS: Conjunctival sac disinfection with 0.01% hypochlorous acid significantly reduced the rate of positive bacterial cultures and colony-forming ability of the conjunctival sac, with statistically significant differences compared with the pre-disinfection period(both P<0.01), and the disinfecting ability of hypochlorous acid was comparable to that of povidone-iodine(χ2=0.811, P=0.368). The scores of ocular symptoms and pain severity in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(both P<0.01). The corneal fluorescein staining and eye redness index in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(all P<0.01). No endophthalmitis occurred in either group of patients. CONCLUSION: As a conjunctival sac disinfectant, 0.01% hypochlorous acid is safe and effective, with minimal discomfort and damage to the ocular surface in patients.

Objective:To investigate the related risk factors of surgical appendectomy after endoscopic retrograde appendicitis therapy (ERAT) in children.Methods:From September 2019 to November 2023 at the Children's Hospital Affiliated to Shandong University,the data from all related children with appendectomy after ERAT were analyzed. The general situation and main clinical manifestations of the children were collected. According to the effect of ERAT,the patients were divided into transfer to surgical group and appendicitis recurrence group by the reasons and time of transfer to surgical treatment. The indexes such as ERAT and reoperation process and pathological types of appendix after operation were collected,and the clinical experience was summarized.Results:Among the 242 children who underwent ERAT,32 cases underwent appendectomy again,including 19 males and 13 females,with an average age of（9.16±2.77）years,and the reoperation rate was 13.2%. The clinical manifestation was abdominal pain (32 cases,100.0%),mainly right lower abdominal pain (28 cases,87.5%),and the main duration was less than 3 months (30 cases,93.8%). Abdominal ultrasound or CT before ERAT mainly indicated appendicitis (11 cases,34.4%) and appendicitis complicated with appendiceal calculus (11 cases,34.4%). There were 9 children in transferred to surgical group,of which 5 cases were transferred to surgery because of ERAT intubation failure,and 4 cases were transferred to surgery because of appendix perforation or abscess. Postoperative pathology showed acute suppurative appendicitis in 5 cases and acute gangrenous appendicitis in 4 cases. There were 23 children in appendicitis recurrence group,whose abdominal pain was relieved after ERAT,but their symptoms were repeated after discharge. After clinical evaluation,they were diagnosed as recurrent appendicitis and underwent surgical appendectomy. Most of them were reoperated within 6 months after ERAT (21 cases,91.3%).Postoperative pathology was mainly chronic appendicitis (10 cases,43.5%).Conclusion:Acute suppurative appendicitis and acute gangrenous appendicitis are prone to catheterization or endoscopic failure during ERAT,and there is a high risk of surgical transfer. ERAT may relieve the symptoms of chronic appendicitis in children. If the symptoms are repeated,surgery is still needed to remove the appendix.

Objective:Applying bibliometrics to analyze the research history, hotspots and trends of Traditional Chinese Medicine (TCM) interventions in edema-related diseases, and to provide reference for the revision of diagnostic and therapeutic criteria for edema in TCM.Methods:The literature about edema treated with TCM was retrieved from CNKI, Wanfang, VIP, CBM from 1 st. Jan 1995 to 25 th. May 2022. CiteSpace and VOSviewer softwares were used to draw the knowledge map, and analyze the co-occurrence relationship and clustering characteristics of the institution, author, keywords and mechanism hotspots. Results:Totally 3 198 articles were included. The annual number of documents issued generally shows a spiral rise trend. Liaoning University of Chinese Medicine published the most articles. Core authors published the most articles were Sun Wei (13 articles); the team with the highest cooperation intensity was Yang Hongtao's team; keywords formed 7 clusters. Hotspot mechanisms included metabolic disorders, immune balance, anti-inflammation, calcium and phosphorus metabolism. Keywords in the past 7 years were membranous nephropathy, chronic heart failure, diabetes, lymphedema etc.Conclusions:The attention paid to the intervention of TCM in the field of edema is generally on the rise, and has decreased in the past two years. The research categories focus on the experience of famous doctors, clinical trials, and mechanistic studies, and nephropathy-related edema has been the focus of research; diabetic nephropathy, chronic heart failure, metabolomics, and immunotherapy are expected to be the focus of attention in the next stage.

Objective:To analyze the efficacy evaluation criteria of the existing TCM treatment for edema RCT research, and to provide reference for the construction of unified standards.Methods:The batabases CNKI, WanFang Data, VIP, CBM, Pubmed and Web of Science were retrieved. The randomized controlled trials for the treatment of edema of TCM research, from September 1, 1993 to July 31, 2022, were screened and included. The content of efficacy evaluation, performed statistics on evaluation standard, the curative effect evaluation indexes, as well as standard composition, usage were extracted. We analyzed the characteristics, application and problems of the existing efficacy evaluation criterion.Results:A total of 123 Chinese articles were included. The included literature involved nephrogenic edema, cardiogenic edema, idiopathic edema, apoplexy limb edema and other edema. In recent years, randomized controlled trials on the treatment of edema by TCM have mainly used four efficacy evaluation criteria. Of which the Guidelines for Clinical Research on New Chinese Medicines (Trial) in 2002 had the highest utilization rate of 29.27%. Secondly, the utilization rate of Standard for Diagnosis and Curative Effect of TCM Diseases and Syndromes was 21.14%. The rest of the criteria were used by less than 6%. While 39.02% of the literature did not use the standards or used self-designed standards. Among the composition of efficacy evaluation indices, the application rate of TCM syndrome or symptom efficacy index was the highest (91.87%), the utilization rate of the Minnesota Living with Heart Failure Questionnaire Indicators was only 4.88%; biochemical tests accounted for a large proportion of Western medical indicators, while the measurement of edema severity was rarely applied. Conclusions:At present, the evaluation criteria of edema curative effect are diversified and insufficiently popularized, which need to be further screened and improved. It is suggested to construct a TCM edema efficacy evaluation model based on the characteristics of edema syndrome, comprehensively evaluate the efficacy from multiple dimensions such as TCM syndromes, western medicine indicators, and quality of life, and improve the scientific indicators.

Objective:To analyze the value of peritumoral vascular invasion (PVI) on the prognosis of patients with osteosarcoma.Methods:A total of 232 patients with primary osteosarcoma from 2007 to 2016 were retrospectively analyzed, including 142 males and 90 females. The average age was 17.9±8.2 years (range, 3-39 years). There were 22 positive and 210 negative cases of PVI, 94 deaths and 138 survivals. Univariate survival analysis (Log-rank test and univariate Cox regression) was used to evaluate the effects of age, gender, PVI status, tumor location, surgical method, sensitivity to chemotherapy, and chemotherapy regimen on the prognosis of osteosarcoma. The indicators with statistically significant differences were included in the multivariate Cox regression model to finally determine the risk factors affecting the prognosis of osteosarcoma. The relationship between PVI status and 5-year survival and the incidence of recurrence or metastasis was evaluated using the Kaplan-Meier method.Results:All patients were followed up for 7.6±4.5 years (range, 0.1-15 years). The differences in sensitivity to chemotherapy (χ 2=9.52, P=0.002), choice of chemotherapy regimen (χ 2=8.87, P=0.012), choice of surgical modality (χ 2=13.50, P<0.001), tumor metastasis rate (χ 2=8.51, P=0.004) and mortality rate (χ 2=5.39, P= 0.020) of PVI positive group and PVI negative group had statistically significant differences. Univariate survival analysis was performed on 232 patients with osteosarcoma (gender, age, PVI status, site of tumor development, surgical modality, sensitivity to chemotherapy, and chemotherapy regimen). Indicators with statistically significant differences were included in a multifactorial Cox regression model. The results showed PVI positive [5-year survival rate: HR=2.02, 95% CI (1.61, 2.79), P=0.010; 5-year recurrence or metastasis rate: HR=2.25, 95% CI (1.55, 3.14), P<0.001], surgical procedure as amputation [5-year survival rate: HR=1.22, 95% CI (0.94, 1.78), P=0.037; 5-year recurrence or metastasis rate: HR=1.58, 95% CI (1.11, 2.23), P=0.026] and poor sensitivity to chemotherapy [5-year survival rate: HR=2.71, 95% CI (1.84, 3.98), P=0.001; 5-year recurrence or metastasis rate: HR=2.52, 95% CI (1.88, 3.45), P<0.001] was associated with poor prognosis. Kaplan-Meier curve showed that the 5-year survival rate of PVI positive group was 34%, which was lower than 68% of PVI negative group. The 5-year recurrence or metastasis rate was 72% in the PVI negative group, which was significantly higher than 38% in the PVI negative group ( P<0.05). Conclusion:The 5-year survival rate of PVI positive group was lower than that of PVI negative group, and the 5-year recurrence or metastasis rate was higher than that of PVI negative group. The presence of microvascular angiosarcoma plugs infiltrating the peritumoral tissue in surgical specimens of osteosarcoma after neoadjuvant chemotherapy is a useful indicator to assess the prognosis of patients with osteosarcoma.

Lipid Droplets/metabolism* ; Bacteria ; Lipid Metabolism

Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.

Background: Bovine papilloma is a neoplastic disease caused by bovine papillomaviruses (BPVs), which were recently divided into 5 genera and at least 24 genotypes. Objectives: The complete genome sequence of BPV type 15 (BPV Aks-02), a novel putative BPV type from skin samples from infected cows in Southern Xinjiang China, was determined by collecting warty lesions, followed by DNA extraction and amplicon sequencing. Methods: DNA was analyzed initially by polymerase chain reaction (PCR) using the degenerate primers FAP59 and FAP64. The complete genome sequences of the BPV Aks-02 were amplified by PCR using the amplification primers and sequencing primers. Sequence analysis and phylogenetic analysis were performed using bio-informatic software. Results: The nucleotide sequence of the L1 open reading frame (ORF) of BPV Aks-02 was 75% identity to the L1 ORF of BPV-9 reference strain from GenBank. The complete genome consisted of 7,189 base pairs (G + C content of 42.50%) that encoded 5 early (E8, E7, E1, E2, and E4) and 2 late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX 2 C zinc-binding domain and a LxCxE motif. Among the different members of this group, the percentages of the complete genome and ORFs (including 5 early and 2 late ORFs) sequence identity of BPV Aks-02 were closer to the genus Xipapillomavirus 1 of the Xipapillomavirus genus.Phylogenetic analysis and sequence similarities based on the L1 ORF of BPV Aks-02 revealed the same cluster. Conclusions The results suggest that BPV type (BPV Aks-02) clustered with members of the Xipapillomavirus genus as BPV 15 and were closely related to Xipapillomavirus 1.

Objective To investigate the expression and clinical significance of transcription factor SOX5 in peripheral blood mononuclear cells (PBMCs) and serum in patients with rheumatoid arthritis (RA). Methods The relative expression of representative genes of the SOX gene family in the PBMCs from RA patients were detected by Real-Time Polymerase Chain Reaction (RT-PCR), and serum levels of SOX5 expression were measured by enzyme-linked immunosorbent assay (ELISA) in 30 RA patients, 27 osteoarthritis (OA) patients and 30 healthy controls (HC). The expression levels of SOX5 in PBMCs were detected by RT-PCR after stimulated with IL-6, TNF-α, IL-1β and IL-17 for 24 hours. The relationship between SOX5 and receptor activator of nuclear factor κB ligand (RANKL) was detected by co-Immunoprecipitation (co-IP). The formation of TRAP-positive cells after silence SOX5 in osteoclast precursor cell treated with RANKL was observed by Tartrate-resistant acid phasphate stain (TRAP). The differences were tested using one-way ANOVA followed by Student-Newman-Keuls post hoc analysis Correlations were analyzed using Pearson's analysis. Results SOX5 was predominantly expressed in the PBMCs of RA as compared with other SOX family genes in PBMC. PBMC levels of SOX5 in RA patients (21±19) were higher than the OA patients (10±8) and healthy control group (5±4)(F=8.343, P<0.01). While, Serum levels of SOX5 in RA patients [(19132±12054) pg/ml were higher than the OA patients [(9065±15172) pg/ml] and healthy control group [(3242±1251) pg/ml] (F=15.31, P<0.01). IL-6, TNF-α, IL-1β and IL-17 led to the up-regulation of SOX5 expression in PBMCs. IL-6, TNF-α, IL-1β promoted the interaction of SOX5 and RANKL in PBMCs. Silencing SOX5 reduced the formation of TRAP-positive cells in osteoclast precursor cell treated with RANKL. Conclusion Our results have proven that transcriptional factor SOX5 regulates the expression of RANKL and participates in the process of RA bone erosion. Inhibition of SOX5 expression may be a new therapy target of RA.