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.

Non-alcoholic fatty liver disease is a common chronic liver disease in clinical practice. In recent years, with increasing social attention to the health of women and the elderly, the prevention and treatment of non-alcoholic fatty liver disease after menopause has increasingly become a research hotspot in metabolic diseases. This study explores the pathogenesis and treatment method of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation" and combined with the physiological and pathological characteristics of postmenopausal women and the Western medicine understanding of non-alcoholic fatty liver disease. We believe that the pathogenesis of non-alcoholic fatty liver disease in postmenopausal women is rooted in the "deficient qi" caused by depletion of liver and kidney essence and blood. The imbalance between the physical and functional aspects of the liver due to this "deficient qi" is the primary factor, while the "stagnation" of phlegm and blood stasis is the manifestation. Furthermore, the "deficient qi" and "stagnation" reinforce each other, with the deficiency leading to stagnation and stagnation exacerbating the deficiency, thus accelerating the progression of the disease. The treatment approach should be one that combines nourishing deficiency and resolving stagnation, addressing both root cause and maifestations. Given the female characteristic of "the liver as the innate organ" and the post-menopausal physiological state of "gradual decline of kidney essence", it is important to focus on nourishing the liver and kidneys, nurturing the liver′s physical body while maintaining its function, and also promoting the circulation of qi, resolving phlegm, and invigorating blood circulation to remove blood stasis. This approach aims to reduce the accumulation of lipids in the liver, offering a new perspective and approach for the treatment of non-alcoholic fatty liver disease in post-menopausal women with traditional Chinese medicine.

This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). : Firstly，estimate the daily new infection rate in Wuhan before January 23，2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 to January 30th if the lockdown measure had been delayed for 7 days，assuming that the daily new infection in Wuhan after January 23 increased in a high，moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that，calculate the number of infection cases imported from Wuhan during this period. Finally，predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. : The daily new infection rate in Wuhan was estimated to be 0.021%，0.026%，0.029%，0.033% and 0.070% respectively from January 19 to January 23. And there were at least 20 066 infection cases in Wuhan by January 23，2020. If Wuhan lockdown measure had been delayed for 7 days，the daily new infection rate on January 30 would have been 0.335% in the exponential growth model，0.129% in the linear growth model，and 0.070% in the logarithm growth model. Correspondingly，there would have been 32 075，24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China，and the number of cumulative confirmed cases as of March 19 in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.
COVID-19 ; China/epidemiology* ; Cities ; Communicable Disease Control ; Humans ; SARS-CoV-2

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 investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50％ by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) ＞5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8％ (748/1 503) patients had residual physical symptoms (PHQ-15＞4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3％,846/1 503),trouble sleeping (50.6％,760/1 503),headache(43.6％,655 / 1 503),constipation,loose stools or diarrhea(41.3％,620/1 503),feeling heart pound or race (37.6％,565/1 503),dizziness (34.0％,511/ 1 503),nausea,gas or indigestion (33.6％,505/1 503),etc.The 75.7％ (555/733) of the physical symptoms (PHQ-15＞4) in residual group was significantly higher than the 25.1％ (193/770;x2=385.38,P＜0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P＜0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.

Objective To explore the incidence of dysphagia and its potential risk factors.Methods From January 2014 to December 2015,a total of 187 patients who underwent single-level anterior cervical spine surgery were recruited in this retrospective analysis study.Specific perioperative data including age,gender,smoking,alcohol use,BMI,estimated blood loss,surgical segment,length of incision,and length of hospital stay were recorded respectively.The Bazaz grading system and the swallowing quality of life (SWAL-QOL) score were used to assess the presence and severity of dysphagia.According to the Bazaz grading system,the patients were divided into dysphagia group and non-dysphagia group 1 week after operation.One-factor x2 test and one-sample t test were used to univariate analyze the two groups of related factors,and select the potential variables for multivariate logistic regression analysis to identify the risk factors leading to dysphagia.Results The number of dysphagia patient was 99 (52.94％) at 1 week after surgery,and 16 (8.56％) at 1 year.The preoperative mean SWAL-QOL score was 65.62±4.41 points,which decreased to 58.72±7.54 points after surgery and rose up to 64.66±5.26 points at the 12-month follow-up.The SWAL-QOL score at 1 week after surgery was correlated with the operative time (r=-0.474;P ＜ 0.001).Multivariate analysis indicated that preoperative tracheal exercise (OR=0.302,95％CI:0.131,0.748),operation time ＜ 60 min (OR=0.407,95％CI:0.190,0.878),and arthroplasty (OR=0.211,95％CI:0.102,0.425) were the independent factors to reduce the incidence of postoperative dysphagia.Conclusion The incidence and severity of dysphagia symptoms after single-level anterior cervical spine surgery gradually decreased with the extension of follow-up time.Preoperative tracheal exercise,shortened operative time and manual artificial disc replacement may be helpful to reduce the postoperative occurrence of dysphagia.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

OBJECTIVETo assess the reproducibility of 3.0 T high-resolution magnetic resonance imaging (HR MRI) for evaluation of atherosclerotic stenosis in the middle cerebral artery (MCA).

METHODSFrom February, 2011 to December, 2013, 66 consecutive patients with MCA-M1 atherosclerotic stenosis (50%-99%) confirmed by digital subtractive angiography (DSA) received examinations with 3.0 T HR MRI for measurement of the vessel area (VA) and lumen area (LA) at the maximum narrow site (VA(narrow) and LA(narrow)) and the reference site (VA(reference) and LA(reference)) as well as the plaque distribution (ventral, dorsal, superior, and inferior). Two independent readers reviewed all the images and one reader reevaluated these images 4 weeks later. The inter- and intra-observer reproducibility was evaluated using the intraclass correlation coefficient (ICC).

RESULTSThe measurements of VA(narrow), VA(reference), and LA(reference) using HR MRI showed excellent inter- (ICC=0.801, 0.843, and 0.808, respectively) and intra-observer reproducibility (ICC=0.811, 0.916, and 0.958, respectively), but the measurement of LA(narrow) had only moderate inter- and intra-observer reproducibility (ICC=0.584 and 0.625, respectively). For plaque distribution analysis (ventral, dorsal, superior, and inferior plaques), HR MRI also showed excellent inter- (ICC=0.856, 0.836, 0.791, and 0.905, respectively) and intra-observer reproducibility (ICC=0.876, 0.827, 0.825, and 0.950, respectively).

CONCLUSIONHR MRI shows good inter- and intra-observer reproducibility in identifying MCA-M1 atherosclerotic plaque distribution and vessel and lumen measurements, but its reliability for lumen area measurement at the maximum narrowing site needs to be improved.