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 explore the effect of timely induction intervention on postpartum urination in primipara during vaginal delivery, so as to provide the evidence for preventing the occurrence of postpartum urinary retention and relieving the pain of primipara.Methods:This study adopted a randomized controlled trial design, and selected 400 cases of primipara who were hospitalized for vaginal delivery in the Obstetric Department of Dalian Women and Children's Medical Group Sports New Town Hospital from June 2021 to September 2022 as the study objects by convenience sampling method. They were divided into the intervention group and the control group with 200 cases each by random number table method, and the control group received routine postpartum care. Instruct active urination within 6 hours after delivery. The intervention received timely induction urination intervention. The general condition and bladder urine volume of the women in the intervention group were evaluated at 2, 4, 6 h after delivery, respectively, and personalized guidance was implemented, including the frequency of massage of the bottom of the uterus, the control of water intake, the selection of methods and timing of inducing urination, etc., and routine postpartum care was given when the women completed their first urination and had no complaints of discomfort. The first urination time, first urination volume, first bladder irritation during the first urination and the incidence of postpartum urinary retention in different periods were compared between the two groups.Results:The patients in the control group were (29.60 ± 3.20) years old, while the patients in the intervention group were (28.81 ± 3.42) years old. The first urination time in the intervention group was (6.89 ± 2.18) h, which was shorter than that in the control group (9.11 ± 3.86) h, and the difference was statistically significant ( t=-2.49, P<0.01). The first urination volume in the intervention group was (322.36 ± 120.15) ml, which was higher than that in the control group (262.93 ± 105.68) ml, and the difference was statistically significant ( t=3.39, P<0.05). The incidence of the first bladder irritation in the intervention group was 22.0%(44/200), which was lower than that in the control group 33.5%(67/200), and the difference was statistically significant ( χ2=6.60, P<0.05). The incidence of postpartum urinary retention within 24 h in the intervention group was 5.5%(11/200), which was lower than that in the control group 11.5%(23/200), and the difference was statistically significant ( χ2=4.63, P<0.05). The incidence of postpartum urinary retention within 1 week in the intervention group was 9.5%(19/200), which was lower than that in the control group 16.5%(33/200), and the difference was statistically significant ( χ2=4.33, P<0.05). There was no significant difference in the incidence of postpartum urinary retention within 24 to 72 h between the two groups ( P>0.05). Conclusions:Timely induction intervention can reduce the incidence of postpartum urinary retention, shorten the time of first urination, increase the volume of first urination and improve the comfort of first urination, which is worthy of clinical application.

OBJECTIVE: To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes. METHODS: From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. RESULTS: The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears). CONCLUSION Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.
Male ; Female ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Rotator Cuff Injuries/diagnostic imaging* ; Rotator Cuff/diagnostic imaging* ; Sensitivity and Specificity ; Ultrasonography ; Magnetic Resonance Imaging/methods* ; Rupture ; Arthroscopy

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Biomarkers ; Humans ; Idiopathic Pulmonary Fibrosis/genetics* ; MicroRNAs/metabolism* ; Sjogren's Syndrome/genetics*

Objective: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. Results: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/immunology* ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Neutralization Tests ; SARS-CoV-2

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

Objective To study the clinical and genetic characteristics of congenital hyperinsulinism (CHI).Method From November 2016 to November 2018,a cohort of 21 patients with CHI were retrospectively reviewed in our hospital.The second generation sequencing was performed on Ion torrent platform to identify the genetic etiology of this disease.Result The average birth weight was 3 748 g.Overall,11 of the 21 patients (52.4％) were large for gestational age (＞ Pg0),and 90.5％ (19/21) onset within 3 days after birth.Seizures occurred in 7 cases (33.3％).Diazine was effective in alleviation in 6 patients,octreotide was effective in 8 patients,and diazine and octreotide were ineffective in 7 patients.11 patients underwent 18-fluoro-l-dopa PET-CT scan,indicating focal islet cell proliferation in 8 patients and diffuse islet cell proliferation in 3 patients.8 focal cases accepted the partial pancreatectomy (7 cases who failed to respond to drug therapy,1 case who received octreotide had significant liver damage),and all of these 8 cases were confirmed with focal islet cell proliferation by postoperative pathology.7 cases had normal glucose level after surgery,while 1 case developed insulin-dependent diabetes.Patients of 3 cases with diffuse islet cell proliferation had no consent for surgery.Gene mutations were identified in 61.9％ (13/21) of patients (12 cases of ABCC8 gene and 1 case of KCNJ11 gene).15 sequence changes were identified (14 in ABCC8 and 1 in KCNJ11).3 new ABCC8 gene mutations (exon13:c.1822C ＞ T,p.Q608X;exon22:c.2691delC,p.W898Gfs*5;exon33:c.4039C ＞T,p.Q1347X),and 1 new KCNJJ11 gene mutation (exon1:c.629T ＞ A,p.H315Y) were firstly reported.Conclusion Partial pancreatectomy is an effective treatment for those CHI not responsive to drug,however,with an attendant risk of developing diabetes.Mutations of ABCC8 gene and KCNJJ11 gene are the main pathogenic genes of CHI.Patients with different gene mutations may have different responses to drug treatment.Therefore,it is necessary to improve gene testing in clinical practice to guide treatment and prognosis.3 new ABCC8 gene mutations and 1 new KCNJJ11 gene mutation were first reported,which expand the spectra of gene mutation.

BACKGROUND: We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH. METHODS: We enrolled 492 consecutive patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated using ROC curves. RESULTS: Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal cutoffs were ≤1.43×105 kU/mL, ≤1.89×104 IU/mL, and ≤3.97×107 IU/mL, with sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5% and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL, >2.29×102 IU/mL, and >8.75×103 IU/mL, with sensitivities and specificities of 72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively. CONCLUSIONS: HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg is an important surrogate marker for predicting EPCH and ENCH.
Area Under Curve ; Biomarkers ; DNA ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Hepatitis, Chronic* ; Humans ; Immunoassay ; Immunoenzyme Techniques ; Real-Time Polymerase Chain Reaction ; ROC Curve