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 role and mechanism of lysine acetyltransferase 8(KAT8)on the prolifera-tion of colorectal cancer cells.Methods The expression of KAT8 in cancerous tissues and adjacent tissues of color-ectal cancer patients was analyzed by RNA-seq data of TCGA database.Cell proliferation was detected by colony-forming unit assays and CCK8.The GEO database was used to analyze the differential genes of KAT8 knockdown cells and control cells and perform functional pathway enrichment analysis.In the colorectal cancer database hosted on cBioPortal,that conducted an analysis examining the correlation between KAT8 and genes in the regulation of N6-methyladenosine(m6A)modification.Western blot technique was employed to assess the protein expression lev-els of KAT8 and METTL3.Results Compared to human normal colorectal tissue,KAT8 was highly expressed in colorectal cancer(P＜0.05).Knockdown or selective inactivation of KAT8 inhibited colorectal cancer cells prolifera-tion(P＜0.05).In colorectal cancer cell lines,knocking down KAT8 reduced m6A modification levels(P＜0.05).Knocking down KAT8 inhibited METTL3 expression(P＜0.05).Over-expression of METTL3 reversed cell prolifera-tion which was inhibited by knockdown KAT8(P＜0.05).Conclusions KAT8 facilitates the proliferation of color-ectal cancer cell lines through regulation of METTL3-mediated m6A modifications.

Objective:To compare the application effects of electric impedance tomography (EIT)-guided positive end-expiratory pressure conventional PEEP and PEEP-fraction of inspired oxygen (FiO 2) table-guided PEEP in the mechanical ventilation of patients with traumatic brain injury (TBI) complicated with acute respiratory distress syndrome (ARDS). Methods:A retrospective cohort study was conducted on the clinical data of 80 TBI patients complicated with ARDS admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from July 2020 to December 2022, including 42 males and 38 females, aged 29-59 years [(42.4±7.8)years]. The Glasgow coma scale (GCS) scores were 3-12 points [(7.7±2.2)points]. According to ARDS classification, 33 were mild, 26 moderate and 21 severe. All the patients were treated with mechanical ventilation according to lung protective ventilation strategy, including 42 patients treated with EIT-guided PEEP (EIT group) and 38 treated with conventional PEEP-FiO 2 table-guided PEEP (conventional group). At 12 hours, 1, 3 and 5 days after ventilation, the optimal PEEP, respiratory mechanics [driving pressure (ΔP), static compliance (C St), mechanical power (MP)], pulmonary gas exchange [arterial blood pH value, arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (P/F)], ventilation distribution [heterogeneity index (GI), regions of interest (ROI)1-4], hemodynamics [heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP)], cerebral perfusion status [intracranial pressure (ICP), regional cerebral oxygen saturation (rScO 2) grading], and treatment outcomes (mechanical ventilation duration, incidence of ventilator-induced lung injury (VILI), length of ICU stay, 6-month survival rate) separately at their optimal PEEP were compared between the two groups. Results:All the patients were followed up for 6 months. The optimal PEEP of the EIT group was (7.4±1.0)cm, (8.2±1.2)cm, (9.8±0.8)cm and (8.4±0.7)cm respectively at 12 hours, 1, 3 and 5 days after mechanical ventilation, which were higher than (7.0±1.0)cm, (7.6±1.0)cm, (9.0±0.6)cm and (7.2±0.5)cm of the conventional group ( P<0.05 or 0.01). At their optimal PEEP separately, at 12 hours, 1, 3 and 5 days after treatment, the ΔP of the EIT group was (7.1±1.3)cmH 2O, (7.7±1.3)cmH 2O, (9.5±1.1)cmH 2O and (6.1±1.3)cmH 2O respectively, which were all lower than (8.9±1.3)cmH 2O, (10.5±1.3)cmH 2O, (11.2±1.2)cmH 2O and (8.7±1.2)cmH 2O of the conventional group respectively ( P<0.05 or 0.01); the C St of the EIT group was (51.5±4.2)ml/cmH 2O, (52.9±4.6)ml/cmH 2O, (55.1±4.3)ml/cmH 2O and (57.5±3.6)ml/cmH 2O, which were all higher than (46.8±3.9)ml/cmH 2O, (47.6±4.4)ml/cmH 2O, (49.9±4.3)ml/cmH 2O and (53.3±3.6)ml/cmH 2O of the conventional group respectively ( P<0.05); the MP of the EIT group was (7.9±1.8)J/min, (8.8±1.3)J/min, (10.6±1.3)J/min and (7.8±0.9)J/min, which were lower than (8.6±1.5)J/min, (9.5±1.0)J/min, (12.2±1.8)J/min and (8.6±0.9)J/min of the conventional group respectively ( P<0.05 or 0.01); the P/F of the EIT group was (207.1±7.1)mmHg, (213.1±6.9)mmHg, (239.3±13.1)mmHg and (255.5±11.8)mmHg, which were all higher than (179.6±7.2)mmHg, (187.8±9.6)mmHg, (212.8±9.6)mmHg and (228.1±12.3)mmHg of the conventional group respectively ( P<0.05 or 0.01); the GI of the EIT group were 0.381±0.013, 0.387±0.012, 0.392±0.010 and 0.395±0.010, lower than 0.403±0.005, 0.406±0.005, 0.409±0.005 and 0.411±0.004 of traditional group respectively ( P<0.01); there were no significant differences in the arterial blood pH value, PaCO 2, ROI1-4, HR, CVP, MAP, ICP, or rScO 2 grading between the two groups (P>0.05). The ventilation duration of the EIT group was (78.5±9.0)hours, which was shorter than (83.1±7.4)hours of the conventional group ( P<0.05). The incidence of VILI was 0.0% (0/42) in the EIT group, which was lower than 7.8% (3/38) in the conventional group ( P<0.05). There were no significant differences in the ICU stay or 6-month survival rate between the two groups ( P>0.05). Conclusions:In mechanical ventilation treatment of TBI complicated with ARDS, the optimal PEEP guided by EIT was higher than that guided by PEEP-FiO 2 table. At this optimal PEEP, the respiratory mechanics and oxygen supply of the patients can be improved more effectively, making regional lung ventilation more uniform, reducing the mechanical ventilation time and decreasing the incidence of VILI without affecting their hemodynamics and brain perfusion.

Objective:To explore the clinical and CT imaging features of immune checkpoint inhibitor-associated pneumonia (CIP) and to improve the early diagnostic ability of CIP.Methods:From June 1, 2020 to October 31, 2021, the clinical data and chest CT images of 2 067 patients with advanced malignant tumor treated with immune checkpoint inhibitor (ICI) in the First Medical Center, Chinese PLA General Hospital were retrospectively analyzed. Patients with CIP were enrolled according to the guidelines for CIP diagnosis, and the incidence, time from the start of medication to the onset of CIP, medication cycle, imaging features, imaging patterns, CT grade and outcomes were analyzed. χ 2 test was used to compare the incidence of CIP in patients with or without basic lung disease. Results:Among 2 067 patients with malignant tumors treated with ICI, 67 patients developed CIP, the incidence of CIP was 3.2%. The incidence of CIP was significantly different between 386 patients with basic lung disease (7.00%, 27/386) and 1 681 patients without basic lung disease (2.4%, 40/1 681) (χ 2=21.32, P<0.001). The time from the start of medication to the onset of CIP was 7-367 d (median 52 days), and the duration of medication was 1-12 cycles (median 2 cycles). The imaging features of CIP presented as ground glass opacities in 54 cases (80.6%), solid nodules in 26 cases (38.8%), consolidations in 25 cases (37.3%) and irregular reticular opacities in 24 cases (35.8%). The main radiologic pattern was organizing pneumonia (OP, 34 cases, 50.7%), and followed by diffuse alveolar damage (DAD) pattern (14 cases, 20.9%). According to CT grading, there were 26 cases in low risk grade, 17 cases in moderate risk grade and 24 cases in high risk grade. Of 43 low-and medium-risk grade cases, 25 were OP pattern, accounting for 58.1%, and among 24 high-risk grade patients, 13 were DAD pattern, accounting for 54.2%. Forty-three of the 52 patients were initially untreated, of which 23 patients progressed, 17 had lesion shrinkage, and 3 had resolution, and relapsed in 8 cases after resolution or drug withdrawal. Conclusions:The imaging manifestations of CIP are mainly ground glass opacities, nodules, consolidations, and irregular reticular opacities. The radiologic patterns are mainly OP and DAD. OP is the most common pattern in low-moderate risk grade CIP and DAD is the most common pattern in high risk grade CIP. Patients with basic lung disease are more likely to get CIP.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

Objective: To predict the efficacy of endoscopic tissue adhesives in the treatment of gastric varices in patients with liver cirrhosis by Nomogram model. Methods: From August 2014 to September 2017, 158 patients with liver cirrhosis caused esophagogastric variceal bleeding and received endoscopic tissue adhesives treatment at Zhongshan Hospital, Fudan University were collected. All patients were followed for 12 months. The primary outcome was rebleeding. The factors of rebleeding after endoscopic treatment of esophagogastric varices were analyzed. Nomogram prognostic model was developed and compared with Child-Pugh grading, computed tomography angiography (CTA) and hepatic venous pressure gradient (HVPG) in prognostic accuracy in rebleeding after endoscopic treatment in liver cirrhosis caused esophagogastric varices. Univariate and multivaricate Cox regression analysis, Kaplan-Meier curve and log-rank test were performed for statistical analysis. Results: During the follow-up, rebleading occurred in 18 cases (11.4%), 37 cases (23.4%) and 49 cases (31.0%) at 2, 6, and 12 months after endoscopic treatment. The results of univariate Cox regression analysis showed the risk factors of rebleeding after endoscopic treatment of gastric varices included gender, alcoholic liver cirrhosis, diabetes mellitus, Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence vs. absence) HVPG (<16 mmHg vs. ≥16 mmHg, 1 mmHg = 0.133 kPa), extensive portal embolism, esophageal varices, type 2 gastric varices, injection points of tissue adhesive (≤3 points vs. > 3 points), injection volume of tissue adhesive (≤ 3 mL vs. > 3 mL) (hazard ratio (HR)=0.575, 2.018, 1.562, 3.433, 2.945, 1.859, 2.743, 0.324, 1.840, 1.477, and 1.716; 95% confidence interval (CI) 0.305 to 1.084, 0.902 to 4.514, 1.753 to 6.724, 1.663 to 5.217, 1.012 to 3.415, 0.852 to 8.830, 0.079 to 1.335, 1.012 to 3.317, 0.839 to 2.602, and 0.935 to 3.152; all P<0.2). The results of multivariate Cox regression analysis indicated that Child-Pugh grade, extraluminal vessels by CTA, and HVPG (HR = 2.095, 95% CI 1.099 to 3.995, P = 0.025) were all independent risk factors of rebleeding after endoscopic treatment of gastric varices (HR=2.665, 2.886, and 2.095; 95% CI 1.339 to 5.300, 1.580 to 5.271, and 1.099 to 3.995; all P<0.05). Kaplan-Meier curves showed that Child-Pugh grade (Grade A vs. B or C), extraluminal vessels on CTA (presence or absent) and HVPG (<16 mmHg vs. ≥16 mmHg) could effectively predict cumulative non-rebleeding rate in one year after endoscopic treatment of gastric varices, and the differences were statistically significant (all P<0.05). Receiver operataring characteristic curve analysis demonstrated that the predictive value of the model combined with Child-Pugh grade, extraluminal vessels on CTA and HVPG was higher than that of Child-Pugh grade and HVPG (AUC=0.746, 0.673 and 0.585; 95% CI 0.662 to 0.829, 0.583 to 0.762, and 0.486 to 0.683; P<0.01, P=0.001 and P=0.089, respectively). Patients were divided into low, medium, and high-risk groups according to the 25th and 75th percentiles of the Nomogram score. The results showed that Nomogram model could effectively distinguish high-risk groups of rebleeding after endoscopic treatment of gastric varices, and the difference was statistically significant (P <0.01). Conclusions Extraluminal vessels on CTA, HVPG and Child-Pugh grade are independent prognostic evaluation indexes of rebleeding after endoscopic treatment of gastric varices. The predictive accuracy of Nomogram model based on these three prognostic factors may be better than Child-Pugh grade and HVPG.

Objective To study the clinical features of hepatic pseudolymphoma.Methods A retrospective study was conducted on 19 patients with hepatic pseudolymphoma who were diagnosed and treated at Zhongshan Hospital in Shanghai from June 2013 to December 2017.Eighteen patients were females and one was a male.The mean age was (55±9) years,range 36 to 68 years.This study mainly analyzed the imaging features,treatment and postoperative results.Results All patients were diagnosed accidentally,and 78.9％ patients did not exhibit any evidence of hepatic B viral infection.A monofocal lesion was found in 14 patients and multifocal lesions in 5 patients.Surgical treatment was performed in all the patients.The lesion size was (1.1±0.4) cm (range 0.5～2.4 cm).Ultrasound revealed hypo-or slightly hypo-echogenicity.On MRI,diffusion weighted imaging showed slight hyperintensity or hyperintensity,all lesions manifested as homogeneous and slightly hyperintensity on T2WI and hypointensity on T1WI.Dynamic enhancement pattern,wash in and wash out,degressive and persistent enhancement were observed in 16(55.2％),12(41.4％),and 1 (3.4％) patients,respectively.More than 70％ of lesions were diagnosed as malignant tumors on preoperative imaging.During a follow-up of 6 ～ 44 months (median:19 months),no patient developed metastasis or recurrence.Conclusions Hepatic pseudolymphoma commonly occurred in women with a small sized lesion.Due to the lack of specific clinical manifestations and imaging findings,preoperative diagnosis was difficult.Surgical resection is still the most optimal treatment.The patients usually have favorable prognosis.

Objective To compare the compressed sensing (CS)and parallel imaging (PI)techniques applied to contrast-enhanced MRI (CE-MRI)scanning of liver and to determine their clinical applicability.Methods Thirty patients with liver mass who underwent the CE-MRI scanning with both CS and PI techniques were recruited in the current study.The SNR of the liver,acquisition time and subjective image quality scores were compared between CS (CE-MRI with CS)and PI (CE-MRI with PI)groups respectively.Results The SNR values of pre-enhancement T1 WI in CS group were lower than those in PI group (1 97.82±32.5 3 vs 204.94±35.28,P＜0.05).However,there was no significant difference in the SNR values of images in equilibrium phase between the two groups (CS vs PI:392.38±72.93 vs 405.03±82.09,P＞0.05).The acquisition time in CS group was significantly shorter than that in PI group [(11.71±0.23)s vs (17.85±0.42)s, P＜0.01].Significantly higher subjective image quality scores were found in CS group than those in PI group (3.54±0.57 vs 2.91±0.80,P＜0.01). Conclusion CS technique may benefit the patients who cannot hold breath well and improve the CE-MRI image quality.

Objective : To investigate the cytotoxicity of slightly acidic electrolyzed water (SAEW) on oral keratinocyte monolayers. Methods: TR146 human keratinocyte monolayers were exposed to SAEW pretreated with bovine serum albumin（BSA）. It was divided into 4 groups, BSA 0 mg/mL (SAEW stock solutsion), BSA 0.5 mg/mL, BSA 1 mg/mL and BSA 2 mg/mL. The relative growth rate (RGR) was measured using a CCK-8 assay at 1 min, 5 min, 15 min, 30 min and 1 h, and the survival rate was measured using a Trypan Blue exclusion assay at 1 h. Results: The CCK-8 assay showed significantly different OD values in the SAEW and negative control groups at different times and FAC concentrations (P<0.05). With increasing FAC concentrations and observation times, the RGR in the SAEW group decreased, and the SAEW showed moderate to severe cytotoxic effects. The OD values in the BSA (0.5~2 mg/mL)-pretreated SAEW and negative control groups were not significantly different at different times or FAC concentrations (P > 0.05); the RGRs of the BSA-pretreated SAEW group all approached 100%, and no cytotoxic effects were observed in the BSA-pretreated SAEW group. The Trypan Blue exclusion assay showed significantly different survival rates in the SAEW and negative control groups at different FAC concentrations (P < 0.05). As the FAC concentration increased, the survival rate in the SAEW group decreased, and SAEW showed moderate to severe cytotoxic effects. The survival rates in the BSA-pretreated SAEW and negative control groups were not significantly different at different FAC concentrations (P > 0.05); the survival rates in the BSA-pretreated SAEW group all approached 100%, and no cytotoxic effects were observed. Conclusion SAEW showed no adverse effects on the viability of dental oral keratinocyte monolayers in vitro in the presence of BSA at concentrations equivalent to that of protein in saliva.