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 investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.

Objective:To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.

ObjectiveTo study the effect of Tanreqing injection （TRQ） on the pulmonary flora in the rat model of chronic obstructive pulmonary disease （COPD）. MethodWistar rats were randomized into control， model， and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ （2 g·kg^-1）. At the end of the experiment， after blood collection from the abdominal aorta of the rats， the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected， and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal， and those of the model group showed neutrophil infiltration， telangiectasia， lung hemorrhage and emphysema in individual cases， and thickening of collagen fibers in the trachea. Compared with the model group， the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group， the model group showcased increased alveolar space （P<0.01）， which was reduced in the TRQ group （P<0.05）. Compared with the control group， the model group showed increased wall thickness （P<0.01）， and the increase was attenuated in the TRQ group （P<0.01）. TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level， the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas， compared with the control group. After treatment with TRQ， the relative abundance of g_Stenotrophomonas increased， and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group， and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD， which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.

Objective:To standardize the management of auditory hallucination symptoms in inpatients with mental illness and develop an expert consensus on the management of auditory hallucinations in hospitalized psychiatric patients.Methods:From March 2023 to July 2023, the Mental Health Committee of the Chinese Nursing Association focused on the key issues in the management of auditory hallucinations symptoms in inpatients with mental illness, based on clinical practice, using literature analysis combined with the work experience of mental health experts, and formed the first draft of the expert consensus on the management of auditory hallucinations in inpatients with mental illness (hereinafter referred to as the consensus). Through 3 rounds of expert consultation and 3 rounds of expert demonstration meeting, the draft was adjusted, revised, and improved.Results:37 experts were included in the Delphi expert consultation, 1 male and 36 females with 39-67(51.48 ± 6.61) years old. The positive coefficients of experts in 3 rounds of Delphi expert consultations were all 100%, and the degrees of expert authority were 0.924, 0.938 and 0.949, respectively. The average importance value of each item was higher than 4.00, the variation coefficient of each item was less than 0.25. The Kendall harmony coefficient of the experts were 0.179, 0.195 and 0.198, respectively (all P<0.05). There were 15, 12, 12 experts in the first, seeond, third rounds of expert demonstration meeting. Finally, a consensus was reached on the recommendation of 4 parts, included auditory hallucination assessment, management format, symptom management implementation, and precautions. Conclusions:The consensus covers all parts of the management of auditory hallucination symptoms in hospitalized patients with mental disorders, which is practical and scientific. It is helpful to guide mental health professionals to standardize the management of auditory hallucination symptoms, improve the quality of nursing and ensure the safety of patients.

Objective:To identify early diagnostic biomarkers for preeclampsia by analyzing the placental and peripheral circulatory transcriptomic data of patients.Methods:Clinical information and microarray expression profiles of preeclampsia patients were sourced from high-throughput gene expression databases. Multi-omics approaches, including differential gene expression analysis, enrichment analysis, and weighted gene co-expression network analysis (WGCNA), were utilized to identify candidate diagnostic markers and explore potential mechanisms of preeclampsia. Subsequently, a combination of machine learning techniques, including random forest, support vector machine, and least absolute shrinkage and selection operator (LASSO), were employed for further screening of these candidates. Finally, the selected diagnostic markers were validated using a peripheral circulation dataset.Results:Differential gene expression analysis revealed 71 upregulated and 21 downregulated genes in preeclampsia. WGCNA linked the onset of preeclampsia with blue and teal modules. Enrichment analysis of candidate biomarkers suggested changes in cell cycle, cellular senescence, and immune-related pathways as primary drivers of preeclampsia. Further refinement through machine learning identified significant upregulation of COL17A1 and DIO2 genes in the peripheral blood of patients, demonstrating robust diagnostic potential. Conclusions:COL17A1 and DIO2 genes can be used as peripheral circulating diagnostic markers for the early diagnosis of eclampsia.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with a complex pathogenesis, which causes the lack of precise and personalized prevention, control, and treatment approaches in clinical practice. Traditional Chinese medicine (TCM) with multiple components acting on multiple targets plays a role in the prevention and treatment of COPD. After evaluating the treatment of cough, dyspnea, and lung distension based on syndrome differentiation in TCM, we summarized the commonly used TCM preparations for treating COPD. These preparations are mainly composed of medicines for clearing interior heat and releasing exterior, tonifying, activating blood and resolving stasis, resolving phlegm, relieving cough and breathlessness, and regulating Qi movement. Because all of them contain a variety of active ingredients such as flavonoids, terpenoids, and phenols, we analyzed the mechanisms of the classic prescriptions alone or in combination with othermedicines or therapeuticmethods. These mechanisms involve counteracting inflammation, oxidative stress, and fibrosis, inhibiting apoptosis, alleviating airway remodeling, and enhancing immunity. Meantime, we summarized the existing problems in the treatment of COPD by TCM. This review provides a scientific basis for the research and treatment of COPD in the future.

Objective:To evaluate the efficacy of continuous infusion of lidocaine via urinary catheter for postoperative analgesia in patients undergoing urological surgery.Methods:Forty male American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-75 yr, with body mass index of 18-25 kg/m 2, scheduled for elective percutaneous nephrolithotomy, were divided into 2 groups ( n=20 each) using a random number table method: continuous infusion of lidocaine through urinary catheter group (group L) and patient controlled intravenous analgesia (PCIA) group (group PCIA). All the patients underwent total intravenous anesthesia, and a matched type of sterile urethral irrigation catheter was inserted after the operation.In group L, 0.5% lidocaine was continuously infused at a rate of 5 ml/h via the urinary catheter, while the equal volume of 0.9% normal saline was continuously infused via the urinary catheter, and PCIA was connected in group PCIA.PCIA solution contained sufentanil 125 μg (diluted to 250 ml in normal saline), and the PCA pump was set up with a 5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 5 ml/h.When visual analogue score was>4, sufentanil 0.05 μg/kg was injected intravenously as rescue analgesic.The development and severity of catheter-related bladder discomfort (CRBD) were recorded immediately at the end of the operation (T 1), and at 6 h (T 2), 24 h (T 3) and 48 h (T 4) after the operation, respectively.Riker sedation-agitation scale (SAS) score was recorded at T 1, 2, and QoR-9 scale was recorded at T 3, 4.The concentrations of serum cortisol (Cor), norepinephrine (NE), epinephrine (E) and blood glucose (Glu) were measured by enzyme linked immunosorbent assay.First off-bed time, exhaust time, length of hospital stay after surgery, and the requirement for rescue analgesia and adverse reactions (nausea and vomiting, respiratory depression, hypotension, skin itching) within 48 h after the operation were recorded. Results:Compared with group PCIA, the incidence of CRBD and the severity were significantly decreased at T 1-4, SAS score was decreased at T 1, 2, QoR-9 score was increased at T 3, 4, Cor, NE, E and Glu concentrations were decreased at T 1-4, the incidence of postoperative rescue analgesia was decreased, first off-bed time, exhaust time and length of hospital stay after surgery was shortened, and the incidence of postoperative nausea and vomiting, respiratory depression, hypotension, skin itching was decreased in group L ( P<0.05). Conclusion:Continuous infusion of lidocaine through the urinary catheter can provide good postoperative analgesia, reduce postoperative stress response and adverse reactions, and facilitate early postoperative recovery in patients undergoing urological surgery.

Objective:To investigate the effects of Xiaoyu-Jiangzhi capsules on blood lipid, carotid artery atherosclerosis (CAA) and plaque in apolipoprotein E knockout (ApoE -/-) mice. Methods:The ApoE -/- mice were fed with high-fat food to establish carotid atherosclerosis model. The ApoE -/- mice were randomly by weight divided into model group, Atorvastatin group, low- and high-dose Xiaoyu-Jiangzhi capsules group. The C57BL/6cnc mice were used as control group and fed with normal diet. The Atorvastatin group was given atorvastatin suspension 1.3 mg/kg, low and high dose groups were given Xiaoyu-Jiangzhi capsule suspension 325 and 975 mg/kg, and the control group and model group were given equal volume of distilled water. The mice were gavaged with 0.1 ml/10 g body weight, once a day, and the weight of mice was recorded weekly. After 12 weeks of continuous intragastric administration, the blood lipid and liver /body weight index of the mice were measured. Carotid arteries were sliced to conduct oil red O staining and VG staining for the pathological analysis. Results:After 12 weeks of drug administration, the weight of mice in the high-dose group was significantly lower than the model group. The level of TC (25.92 ± 4.21 mmol/L vs. 30.39 ± 4.67 mmol/L) and LDL-C (7.97 ± 2.14 mmol/L vs. 10.26 ± 1.97 mmol/L) in the high-dose group significantly decreased ( P<0.05), the level of HDL-C in the low and high-dose group significantly increased ( P<0.05). The pathological results showed that after 12 weeks of administration, the carotid artery lipid deposition blockage rate in the Atorvastatin group and the high dose group were significantly smaller than the model group( P<0.05), and no vascular plaque has been formed. Conclusion:The Xiaoyu-Jiangzhi capsules could reduce LDL-C, increase HDL-C levels, reduce the constriction of arterial stenosis and slow down the formation process of carotid plaque.

Objective To evaluate the effect of Yiqifumai mixture on ventricular arrhythmia induced by isoproterenol. Methods Forty spontaneous hypertensive rats (SHR) were randomly divided into a control group and a Chinese medicine (TCM) group with 20 rats in each group. The control group was given distilled water 3.48 mL·kg-1·d-1, and the TCM group was given Yiqifumai mixture (composition: Codonopsis pilosula, Rhizoma coptidis, Pinellia ternate, Euonymus alatus, Rhizome of chuanxiong, Salvia miltiorrhiza, Radix paeoniae rubra, Radix paeonia alba, Licorice, Zizyphus jujuba, Polygala tenuifolia) 3.48 mL·kg-1·d-1, both groups were administered continuously for 7 days. Arrhythmia was induced by subcutaneous injection of isoproterenol 100 mg/kg into the neck 1 hour after the last administration in both groups. ECG telemetry was carried out for 2 hours to record whether single premature ventricular contraction (SP), paired premature ventricular contraction (PP) and ventricular tachycardia (VT) occurred in the control group and the TCM group, and the incidences, numbers and times of their occurrences were registered. Results There were no statistical significant differences in SP incidence (SPR), PP incidence (PPR), VT incidence (VTR) between the control group and TCM group at 1 hour and 2 hours [1 hour SPR was 90% (18/20) vs. 80% (16/20), PPR was 65% (13/20) vs. 65% (13/20), VTR was 45% (9/20) vs. 40% (8/20); 2 hours SPR was 100% (20/20) vs. 100% (20/20), PPR was 75% (15/20) vs. 75% (15/20), VTR was 65% (13/20) vs. 60% (12/20); all P > 0.05]. After 1 hour of ECG telemetry, the number of SP in the TCM group was significantly lower than that in the control group [numbers: 10.00 (4.00, 11.00) vs. 16.00 (8.50, 42.50), P < 0.05]; after 2 hours of ECG telemetry, the numbers of SP, PP and VT in the TCM group were significantly lower than those in the control group [SP (numbers), 27.00 (15.50, 38.00) vs. 37.50 (24.00, 74.50), PP (numbers), 5.00 (3.00, 8.00) vs 7.00 (5.00, 11.00), VT (numbers), 2.50 (1.25, 4.00) vs. 7.00 (4.50, 11.00), all P <0.05]. After 1 hour and 2 hours of ECG telemetry, the occurrence times of SP, PP and VT were slightly longer than those in cintrol group, but there were no significant differences between the two groups [1 hour: SP (minutes) was 4.35 (3.65, 9.90) vs. 3.66 (1.12, 9.52), PP (minutes) was 35.56 (26.78, 46.42) vs. 23.39 (11.74, 43.42), VT (minutes) was 22.31 (6.25, 30.02) vs. 14.27 (8.79, 31.38); 2 hours: SP (minutes) was 7.06 (3.65,12.29) vs. 4.09 (1.38, 14.11), PP (minutes) was 46.40 (33.88, 71.39) vs. 33.81(14.54, 46.20), VT (minutes) was 75.49 (59.37, 96.63) vs. 60.55 (24.65, 86.48), all P > 0.05]. Conclusion Yiqifumai mixture has the effect of anti-arrhythmia induced by isoproterenol and its effect in longer term use is more significant.