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.

OBJECTIVES: To analyze the differences in the prognosis of gastric signet ring cell carcinoma (SRCC) among different races using the US Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We analyzed the data of patients with gastric SRCC from the SEER database from 2000 to 2020, and divided the patients into cohorts of whites, blacks, Asians or Pacific Islanders, American Indians/Alaska Natives according to their race. The prognosis and treatment of the cohorts were evaluated using baseline demographic analysis, Kamplan-Meier survival curve, and nomogram analysis. RESULTS: We analyzed the data of a total of 2058 patients, including 8.6% blacks, 72.4% whites, 16.6% Asians or Pacific Islanders, 1.0% American Indians/Alaska Natives, and 1.4% other races. The tumor grade varied among different races, and the prevalence and survival rates of patients differed significantly across races. The differences in the white cohort were the most prominent, and all the differences were statistically significant (P<0.05). Racial differences were also noted in patient management and prognosis. CONCLUSIONS There are racial differences in tumor grades and prognosis of gastric SRCC, and these differences provide evidence for optimizing clinical diagnosis and treatment strategies for this malignancy.
Aged ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Signet Ring Cell/therapy* ; Databases, Factual ; Prognosis ; Racial Groups ; SEER Program ; Stomach Neoplasms/therapy* ; Survival Rate ; United States/epidemiology* ; White ; Asian American Native Hawaiian and Pacific Islander ; American Indian or Alaska Native ; Black or African American

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

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.

Patients with ovarian cancer are prone to malignant bowel obstruction and often require surgical treatment, which could possibly lead to postoperative complications including enterocutaneous fistula. The treatment of enterocutaneous fistula requires phased and gradual approaches. Medical nutrition support is an important part of enterocutaneous fistula management, of which personalized strategies need to be developed based on factors such as the location of the intestinal fistula, fistula output, organ function, and nutritional status of patients. Here we report a case of nutritional therapy for a patient with recurrent ovarian cancer complicated with malignant bowel obstruction who developed a proximal enterocutaneous fistula after surgery. The relevant literature are reviewed, with the aim of informing nutritional therapy for enterocutaneous fistula.

Objective:To investigate, assess and analyze the attitude and competency in terms of clinical nutrition and intentions of teaching and examination methods, and their basic nutrition knowledge.Methods:A cross-sectional survey was conducted using stratified sampling method among first- to third-year undergraduate nursing students. A questionnaire was designed to cover several domains including attitude towards clinical nutrition, the importance of nurses in clinical nutrition practice, self-confidence in implementing nutrition counseling, knowledge of nutrition, and preference about teaching and examination methods, each of which was categorized into the 5 levels of strongly disagree/very unconfident, disagree/unconfident, unsure, agree/confident, and strongly agree/very confident (i.e., a scale of 1-5). Besides, the nutrition knowledge was examined through multiple choice questions.Results:A total of 262 students completed the survey. 252 (96.2%) students agreed that the nurses should be involved in the planning and promotions of patient healthy lifestyle, acknowledged the importance of nurses in clinical nutrition practice, and were willing to learn. However, there was overall under-recognition of nutrition, with the score of 4.07±0.92 in females and 3.63±0.84 in males ( P=0.017), whereas no significant difference was seen across grades (3.54±0.98, 3.96±0.83 and 3.87±0.60 for Grade 1,2 and 3 students, respectively, P=0.107). Students considered current nutritional training as inadequate and had low self-confidence in implementing patient nutritional education. The test showed overall poor knowledge on nutrition, with a mean score of 12.82/20 and a pass rate of 68.7%. The students in Grade 3 (14.61±2.45) performed better than those in Grade 1 and 2 (11.91±3.26 and 12.38±3.64, P=0.001). Students who have received nutritional training performed better than those who have not (13.32±3.52 vs. 11.28±3.52, P=0.004). However, there was no significant correlation between the test scores and the attitude towards nutrition, self-confidence in nutrition education and the attention to nutrition ( P>0.05). Regarding teaching methods, most students (55.7%) preferred the integrated method of traditional method, clinical case study, and flipped classroom. Conclusions:Undergraduate nursing students recognize the importance of nutrition in healthcare and confirm the significance of nurses in patient nutritional education. Nursing students have a positive attitude towards nutritional learning but have limited recognition of nutrition, low self-confidence in patient nutritional education, and inadequate knowledge. Clinical practice-based teaching methods can be integrated into their curriculum to improve the quality of nutrition programs.

Objective:To evaluate the body composition of ulcerative colitis (UC) patients by bioelectrical impedance analysis (BIA) and explore the correlation between body composition indices and disease activity, laboratory indices, and readmission.Methods:Patients with active UC hospitalized in the Department of Gastroenterology of Peking Union Medical College Hospital were enrolled continuously, and age and sex ratio-matched healthy volunteers were recruited through recruitment posters. Body composition was measured via BIA. Appendicular skeletal muscle index (ASMI) and trunk skeletal muscle index (TSMI) were calculated and adjusted for height (m 2). Muscle function was evaluated via handgrip strength. Moreover, patients were followed up after discharge and the readmissions due to recurrence or aggravation of UC were recorded. Results:This study enrolled 62 UC patients and 38 healthy volunteers. TSMI decreased significantly ( P<0.001) while ASMI showed no significant difference in male patients compared with healthy controls. ASMI ( P<0.001) and TSMI ( P=0.002) in female patients were significantly lower than those in healthy controls. Compared with patients with normal TSMI, a larger proportion of patients with low TSMI tended to show severe disease activity ( P=0.075), while no such trend was observed in patients with low ASMI. Handgrip strength and phase angle were significantly positively correlated with ALB in UC patients ( P<0.05). The proportion of patients with readmission was significantly higher in the low phase angle group than that in the normal phase angle group (58.3% vs. 22.0%, P=0.040). Conclusions:There were abnormal body composition and gender differences in UC patients. TSMI correlated better with clinical characteristics than ASMI in UC patients. Low phase angle might be predictive for readmission in UC patients.

Objective To investigate the mechanism by which Colony Stimulating Factor-1(CSF1)inhibits apoptosis in neurons subjected to oxygen-glucose deprivation(OGD).Methods Primary rat cortical neurons were divided into the OGD damaged neuron model group(OGD group),the rh-CSF1 intervention group(rh-CSF1 group),and control group.The sample size for each group was 3.After intervention with recombinant human CSF1(rh-CSF1),neuronal apoptosis rate and intracellular ATP content,reactive oxygen species levels,mitochondrial membrane potential,and mitochondrial DNA copy number were measured.The content of malondialdehyde within mitochondria and the activity of superoxide dismutase were also assessed.Results Intervention with rh-CSF1 increased mitochondrial membrane potential(0.55±0.03 vs.0.43±0.06,P<0.01),mitochondrial DNA copy number(0.88±0.05 vs.0.72±0.06,P<0.05),ATP content[(15.70±0.99)mmol/mg vs.(11.70±1.00)mmol/mg,P<0.01)],and superoxide dismutase[(18.47±1.38)U/mg vs.(14.78±1.81)U/mg,P<0.05)]activity in neurons injured by OGD.It also reduced levels of rectivereactive oxygen species(3.64±0.21 vs.4.45±0.33,P<0.05)and malondialdehyde within mitochondria[(2.13±0.19)mmol/mg vs.(2.78±0.20)mmol/mg,P<0.05)],and inhibited neuronal apoptosis(10.12±0.78 vs.17.04±1.23,P<0.01)Conclusion rh-CSF1 may alleviate the damage in neurons induced by OGD by improving mitochondrial function,reducing oxidative stress,and inhibiting cell apoptosis.

Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.

Object:To conduct a scoping review of maternal readiness for hospital discharge, so as to provide references for future clinical research and practice on maternal and infant care.Methods:Using the scoping review guidelines of Joanna Briggs Institute in Australia as the methodological framework, the relevant studies on maternal readiness for hospital discharge were searched by computer on PubMed, Web of Science, Scopus, CNKI, Wanfang Database, Chinese Science and Technology Journal Database and China Biology Medicine disc. The search period was from the establishment of the databases to October 20, 2022.Results:A total of 24 artiles were included. The influencing factors of maternal readiness for hospital discharge included sociodemographic factors, maternity factors, psychological factors, children factors, family social factors, medical staff related factors and other factors. The intervention measures of maternal readiness for hospital discharge included the establishment of discharge preparation team, the measures from hospital admission to prenatal period, the measures from postpartum to the day of discharge and the measures after discharge. There were many kinds of scales for maternal readiness for hospital discharge, and there was no unified assessment standard.Conclusions:The level of maternal readiness for hospital discharge is different, and its influencing factors should be paid attention to. In the future, further research can be conducted on intervention measures and evaluation standards for maternal discharge readiness, providing references for improving the level of maternal discharge readiness.