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.

Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.

In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences· Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.

Objective:To test and evaluate the reliability and clinical effectiveness of osteoporotic thoracolumbar fracture (OTLF) scoring and classification system.Methods:A multicenter retrospective case series study was conducted to analyze the clinical data of 530 OTLF patients admitted to 8 hospitals including Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to June 2022. There were 212 males and 318 females, aged 55-90 years [(72.6±10.8)years]. There were 4 patients with grade C and 18 with grade D according to American Spinal Injury Association (ASIA) classification. According to the osteoporotic thoracolumbar injury classification and severity (OTLICS) score, all patients had an OTLICS score over 4 points and required surgical treatment. Among them, 410 patients had acute symptomatic OTLF (ASOTLF), including 24 patients with type I, 159 type IIA, 47 type IIB, 31 type IIC, 136 type IIIA, 8 type IIIB, 2 type IV (absence of neurological symptoms) and 3 type IV (presence of neurological symptoms), and 120 patients had chronic symptomatic OTLF (CSOTLF), including 62 patients with type I, 21 type II, 17 type III, 3 type IV (reducible under general anesthesia), 9 type IV (not reducible under general anesthesia), 1 type V (reducible under general anesthesia), 5 type V (presence of neurological symptoms), and 2 type V (not reducible under general anesthesia). Surgical procedures included percutaneous vertebroplasty (PVP), positional repositioning plus PVP, percutaneous kyphoplasty (PKP), posterior open reduction combined with bone graft fusion and bone cement augmented screw internal fixation, posterior open reduction combined with decompression, bone graft fusion and bone cement augmented screw internal fixation, and posterior open reduction combined with osteotomy and orthopedics, bone graft fusion and bone cement augmented screw internal fixation. A weighted Kappa was used to test the interobserver and intraobserver reliability of the OTLICS score, the ASOTLF classification, and the CSOTLF classification. The visual analog scale (VAS), Oswestry disability index (ODI), ASIA classification were compared before, at 1 month after surgery and at the last follow-up. Incidence of postoperative complications was observed.Results:The percentage of mean interobserver agreement for OTLICS staging was 93.4%, with a mean confidence Kappa value of 0.86, and the percentage of mean intraobserver agreement was 93.0%, with a mean confidence kappa value of 0.86. The percentage of mean interobserver agreement for ASOTLF staging was 94.2%, with a mean confidence Kappa value of 0.84, and the percentage of mean intraobserver agreement was 92.5%, with a mean confidence Kappa value of 0.83. The percentage of mean interobserver agreement for CSOTLF subtyping was 91.9%, with a mean confidence Kappa value of 0.80, and the percentage of mean intraobserver agreement was 91.3%, with a mean confidence Kappa value of 0.81. All the patients were followed up for 6-12 months [(9.0±2.1)months]. The VAS and ODI scores were significantly lower in patients with ASOTLF and CSOTLF classifications at 1 month after surgery and at the last follow-up than those before surgery (all P<0.05). The VAS scores in patients with ASOTLF types IIA, IIB, IIC, IIIA, and IV were significantly lower at the last follow-up than that at 1 month after surgery; the ODI scores in patients with ASOTLF types I, IIA, IIB, IIIA, IIIB and IV were significantly lower at the last follow-up than those at 1 month after surgery. The VAS scores in patients with CSOTLF types II, III, IV, and V were significantly lower at the last follow-up than those at 1 month after surgery, and the ODI scores in patients with all CSOTLF types were significantly lower at the last follow-up than those at 1 month after surgery (all P<0.05). Two patients with ASIA grade C recovered to grade D, and the rest recovered to grade E at the last follow-up ( P<0.01). No major vessel or nerve injury or internal fixation failure was found during follow-up. There were 18 patients with cement leakage, none of whom showed relevant clinical symptoms. There were 35 patients with new vertebral fractures, all of whom recovered well after symptomatic treatment. Conclusions:The OTLICS score, ASOTLF classification and CSOTLF classification have a high degree of reliability. Application of stepwise treatment for patients with different levels of injury according to the scoring and classification system can reduce pain, promote recovery of the spinal function, and reduce complications, which is of some significance in guiding the selection of clinical treatment.

Objective:To explore the effect of umbilical vein catheterization (UVC) on portal vein blood flow velocity (PBFVe) and its relationship with gastrointestinal (GI) complications in neonates.Methods:A prospective study was conducted on neonates with indications for UVC and achieving one-time successful catheterization at Gansu Provincial Women and Child-care Hospital from March 2019 to March 2021. Successful UVC was defined as the umbilical catheter reaching the entrance of the inferior vena cava and right atrium through the ductus venosus. PBFVe was measured by bedside ultrasound before and after UVC. All subjects were divided into two groups as those with GI complications anytime from insertion to withdrawal (complication group), and those with no GI complications (no complication group) to compare the PBFVe value before UVC and the percentage of decrease in PBFVe after UVC. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were used to analyze the risk factors of GI complications and the predictive value of the percentage of decrease in PBFVe after UVC.Results:Of 91 subjects included, 59.3% (54/91) had no GI complications, and 40.7% (37/91) had. After UVC, PBFVe was decreased than before in neonates both with and without GI complications [(11.3±1.8) vs (14.7±2.4) cm/s; (12.4±1.7) vs (14.2±1.8) cm/s, t=－16.92 and－17.62, respectively, both P<0.05]. PBFVe before UVC were similar between the two groups. However, the complications group had a lower PBFVe after UVC ( t=－2.98, P=0.004) and a higher percentage of decrease in PBFVe [(22.5±6.0)% vs (12.6±4.9)%, t=8.65, P<0.001] when compared with the no complications group. Multivariate logistic regression analysis showed that the body weight was the protector of GI complications ( OR=0.294, 95% CI:0.089-0.974, P=0.045), and the percentage of decrease in PBFVe was the risk factor ( OR=1.478, 95% CI:1.249-1.749, P<0.001). The area under the curve of the percentage of decrease in PBFVe for predicting GI complications was 0.919 (95% CI:0.843-0.966, P<0.001). The cut-off value was 16.9% with a sensitivity of 89.2% and a specificity of 85.2%. Conclusions:UVC can reduce the PBFVe of neonates. The more the PBFVe decreases, the greater the possibility of GI complications.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Objective:To analyze the prognostic factor of arteriovenous fistula (AVF) maturation and provide the theoretical basis for the hemodialysis patients' AVF surgery.Methods:Retrospective investigation was conducted on patients that underwent AVF surgery in Wuhan Central Hospital from January 2017 to June 2019 as study subjects to investigate the prognostic factor of AVF maturation. The general information, hematological indicators, preoperative and postoperative ultrasound data of patients were recorded. Patients were divided into mature group and immature group according to the physical examination status, functional status and postoperative color doppler ultrasound data after AVF surgery, and the differences between the two groups were compared. Logistic regression analysis was used to analyze the prognostic factors of AVF maturation, and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of each factor for AVF maturation.Results:A total of 164 patients were included, including 110 patients in the mature group and 54 patients in the immature group. There were statistically significant differences between the two groups in surgical vein diameter, surgical artery diameter, brachial artery flow, cardiac ejection fractions, systolic blood pressure, diastolic blood pressure and history of diabetes (all P<0.05), while there were no statistically significant differences in other indicators such as gender, age, etc. Logistic regression analysis showed that preoperative surgical artery diameter (every increase by 0.1 mm, OR=1.402, 95% CI 1.159-1.697, P=0.001), surgical vein diameter (every increase by 0.1 mm, OR=1.341, 95% CI 1.176-1.528, P<0.001), cardiac ejection fraction (every increase by 5%, OR=1.184, 95% CI 1.087-1.289, P<0.001), systolic blood pressure (every increase by 10 mmHg, OR=1.407, 95% CI 1.103-1.796, P=0.006), brachial artery flow (every increase by 10 ml/min, OR=1.047, 95% CI 1.004-1.091, P=0.034) and history of diabetes ( OR=0.271, 95% CI 0.103-0.715, P=0.008) were the independent influencing factors for AVF maturation. ROC curve showed that preoperative surgical artery diameter ( AUC=0.728, 95% CI 0.643-0.839, P<0.001), surgical vein diameter ( AUC=0.762, 95% CI 0.686-0.839, P<0.001), cardiac ejection fraction ( AUC=0.711, 95% CI 0.626-0.796, P<0.001) were the important indicators for predicting AVF maturation. Conclusions:Preoperative surgical artery diameter, surgical vein diameter, cardiac ejection fraction and diabetes mellitus are the prognostic factors of AVF maturation. In preoperative vascular assessment, attention should be paid to the diameter of target arteries and veins, as well as to the cardiac function and diabetes mellitus of patients.

Objective:To explore the effect of the angle between sagittal part of left portal vein and ductus venous(AsLPVDV), and the diameter of ductus venous(DDV) on the success rate of umbilical venous catheterization (UVC) in neonates.Methods:This was a retrospective study including 80 neonates requireing UVC in Gansu Provincial Women and Child-care Hospital from April 2020 to January 2021. According to the results of UVC, they were grouped into the success group(successful insertion of catheter, n=76) and failure group(failed to insert, n=4), or one-time success group (successful after first insertion attempt, n=43) and non-one-time success group(successful after several attempts or failed to insert, n=37). The AsLPVDV and the DDV were measured before UVC by bedside ultrasound. For those with obstruction of catheterization were guided by pressing the abdomen in right side recumbent position under real-time ultrasound monitoring. The success rate of UVC and the differences of AsLPVDV and DDV among different groups were compared. Chi-square test, t test, or U test were adopted for the comparison among groups. Receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the AsLPVDV and the DDV in predicting the one-time success of UVC. Results:The total success rate of UVC was 95%(76/80) and the one-time success rate was 53.8%(43/80). A larger AsLPVDV and DDV were observed in the success group compared with the failure group [(142.2±8.3)° vs (133.6±3.2)°, (3.0±0.4) vs(1.8±0.4) mm, t=6.284 and 2.064, both P<0.05] as well as in one-time success group compared with the non-one-time success group [(147.5±6.2)° vs (135.2±4.7)°, (3.1±0.3) vs (2.8±0.6) mm, t=9.956 and 2.939, both P<0.05]. Area under the curve of AsLPVDV and DDV in predicting one-time success of UVC were 0.944(95% CI:0.869-0.983) and 0.811 (95% CI:0.708-0.890), respectively. The cut-off value was 140.4° for AsLPVDV and 2.9 mm for DDV, with the sensitivity of 93.0% and 90.7%, and specificity of 91.9% and 64.9%, respectively. Conclusions:The success rate of UVC is related to AsLPVDV and DDV. AsLPVDV is of high value in predicting the one-time success of UVC.

Objective To investigate the effect of U50488H on the ultrastructure and organ function in septic shock rats. Methods Forty SD male rats were randomly(random number) divided into 5 groups: sham group, septic shock group, U50488H+septic shock group, nor-BNI+U50488H+septic shock group, and nor-BNI+septic shock group, with 8 rats in each group. Cecal ligation and puncture (CLP) was performed to induce septic shock in the septic shock group. Rats in the U50488H+septic shock group were treated with U50488H injection by intravenous at the shock point, and other procedures were the same as the septic shock group. Rats in the nor-BNI+U50488H+septic shock group were treated with nor-BNI injection by intravenous 3.5 h after abdomen closed, and other procedures were the same as the U50488H+septic shock group. Except for U50488H injection, rats in the nor-BNI+septic shock group received procedures the same as the nor-BNI+U50488H+septic shock group. Albumin, cardiac troponin I (cTnI) and N terminal pro B type natriuretic peptide (NT-proBNP) in serum were measured at abdomen-closed, 3, 6, and 12 h after CLP. The changes of histology and ultramicro structure under electron microscope of lung, heart, liver and kidney of rats were observed at 12 h after CLP. Statistical analysis was performed using SPSS 19.0. Comparison among groups was carried out using ANOVA, and Student's t-test was used for multiple comparisons as post-hoc. Results At 6 and 12 h of CLP, serum albumin of the septic shock group were significantly lower than those of the sham group (P<0.01), while those in the cTnI and NT-pro BNP groups were higher at 3, 6, and 12 h of CLP (P<0.01). Compared with the septic shock group, serum albumin of the U50488H+septic shock group increased significantly (P<0.01), whereas the serum levels of cTnI and NT-pro BNP decreased remarkably at 3, 6 and 12 h of CLP (P < 0.05, P < 0.01, respectively). Compared with the sham group, the alveolar wall was severely damaged, the alveolar septum and blood vessel wall were thickened obviously; the myocardial fiber was swollen, necrotic, and the infiltration of central granulocyte was increased significantly; hepatocyte showed edema, vacuolar-like steatosis, fatty degeneration, spotty and focal necrosis; and slight edema and vacuolar degeneration were found in the glomerulus endothelial in the septic shock group. Compared with the septic shock group, the ultrastructural damage of the lung, heart, liver and kidney of the U50488H+ septic shock group was significantly improved. All the above effects of U50488H could be blocked by nor-BNI (a selective κ-opioid receptor antagonist) (P<0.01). Conclusions U50488H can promote the recovery of serum albumin, and protect organ function in septic shock rats.

Objective To evaluate the relationship between the changes in gray matter volume ( GMV) in different brain regions in the early postoperative period and the development of chronic pain after radical mastectomy. Methods Forty-four American Society of Anesthesiologists physical status Ⅰ or Ⅱpatients, aged 25-64 yr, scheduled for elective radical mastectomy, were divided into 3 groups according to the numeric rating scale ( NRS) score within 3 months after surgery: severe chronic pain group ( NRS score≥3, group SEP), slight chronic pain group (NRS score=1 or 2, group SLP) and no chronic pain group ( NRS score=0, group NP ) . All the patients underwent whole brain MRI scan within 7 days after surgery. MRI data processing and analysis were carried out using SPM8-based VBM software package and REST 1. 8 software. Results There were 17 cases in group SEP, 10 cases in group SLP and 17 cases in group NP. Compared with group NP, GMV in the right postcentral gyrus was significantly decreased, and GMV in the right superior frontal gyrus was increased in group SEP ( P＜0. 01) . Conclusion The changes in GMV in the right postcentral and superior frontal gyrus in the early postoperative period may be related to the development of chronic pain after radical mastectomy.