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.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

Objective:To analyze the clinical features, diagnosis, treatment and prognosis of nodular fasciitis (NF) in the head and neck.Methods:Seven cases of primary NF in the head and neck admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 1990 to 2022 were retrospectively analyzed, including 3 males and 4 females, aged from 2 to 67 years, and the location, course of disease, clinical manifestations, imaging findings, and treatment results of the disease were summarized.Results:Of the 7 patients, the primary sites were respectively nasal vestibule, paranasal sinus, nasal dorsum, sella turcica and clivus, neck, subglottis, and tonsil. Three cases presented with rapidly growing subcutaneous painless masses within 2 months, 1 case presented with hemoptysis, hoarseness and asthma for 28 days, 1 case presented with blood in the nasal discharge for 2 months, 1 case presented with headache for 1 month, and 1 case was found to have tonsillar neoplasms on physical examination for 3 days. CT was performed in 5 patients and the lesions showed soft tissue density shadows, and MRI was also performed in 2 of them, which showed T1 isointensity or T2 slightly long abnormal signal shadows. All patients underwent simple surgical resection of the mass. The patients were followed up for 13 months to 10 years, and none had recurrence.Conclusion:Primary NF in the head and neck is rare, with atypical clinical symptoms and imaging findings. Surgery is the mainstay of treatment for NF with good results.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Objective:To evaluate the effects of sugammadex on the quality of recovery after laparoscopic bariatric surgery in severely obese patients.Methods:One hundred and eighty patients, aged 18-65 yr, with body mass index ≥ 40 kg/m 2, undergoing elective laparoscopic bariatric surgery, of American Society of Anesthesiologists physical status Ⅲ, were enrolled and divided into 2 groups ( n=90 each) by the random number table method: sugammadex group (S group) and neostigmine group (N group). Before anesthesia, bilateral T 6 and T 9 paravertebral nerve blocks were performed, and 0.33% ropivacaine 15 ml was injected on each side.When the reappearance of T 2 was monitored under train-of-four (TOF) stimulation after the end of surgery, and sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.04 mg/kg and atropine 0.02 mg/kg were intravenously injected in N group.After the patient was transferred to the general ward, flurbiprofen axetil 50 mg was injected intravenously every 12 h, and oxycodone and flurbiprofen axetil were used for patient-controlled intravenous analgesia at the same time.When the numerical rating scale (NRS) score ≥4 and the analgesic pump was ineffective, bilateral T 7 paravertebral nerve block was performed for rescue analgesia, and 0.33% ropivacaine 15 ml was injected on each side.The postoperative quality of recovery was assessed by the 15-item Quality-of-Recovery scale before operation and at 24 h after operation.The TOF ratio ≥ 0.9 and extubation time were recorded.The SpO 2 at the time of transfer to post-anesthesia care unit (PACU), the lowest SpO 2 and occurrence of SpO 2 < 92% during PACU were recorded.The occurrence of residual muscle relaxation and Ramsay sedation score were recorded at 30 min after entering PACU.The time of PACU stay, time to the first off-bed activity and length of hospital stay were recorded.The cumulative consumption of oxycodone, requirement for rescue analgesia, dizziness, nausea and vomiting, hypoxemia, and pulmonary complications were recorded within 48 h after operation. Results:There were no significant differences in the total score of 15-item Quality-of-Recovery scale before surgery and at 24 h after surgery, cumulative consumption of oxycodone within 48 h after surgery, rate of rescue analgesia, and incidence of dizziness, nausea and vomiting, hypoxemia and pulmonary complications between the two groups ( P>0.05). Compared with N group, the scores of the three recovery indicators (feel energized with enough rest, engagement in work or family activities, and tension and anxiety) were significanatly increased, time to TOF ratio ≥ 0.9, extubation time, time of PACU stay, time to the first off-bed activity and length of hospital stay were shortened, and the incidence of residual muscle relaxation was decreased in S group ( P<0.05). Conclusions:Antagonizing residual muscle relaxation with sugammadex is helpful for the recovery of severely obese patients after laparoscopic bariatric surgery.

To reveal the pharmacological mechanism of 3-arylcoumarin derivative 3-(4′-hydroxyphenyl)-6-hydroxycoumarin (SJ-6) against vascular calcification, advanced glycation end products (AGEs) were used to induce the calcification of human aortic vascular smooth muscle cells (HCASMCs), and calcification was identified by alizarin red staining and quantification.The effects of SJ-6 on alkaline phosphatase (ALP) activity, cell proliferation rate, calcium content, and total reactive oxygen species (ROS), superoxide dismutase (SOD), AGEs, and tetra methylethlene diamine proteinase factor-α (TNF-α), interleukin-6 (1L-6), interleukin-β (1L-β), runt-related transcription factor 2 mRNA (Runx2 mRNA), the receptor of advanced glycation endproducts (RAGE), nuclear factor kappa-B (NF-κB), napdh oxidase-1 (NoX-1), protein kinase C(PKC), protein kinase b(AKT), p38 mitogen-activated protein kinase (p38 MAPK), and smooth muscle actin-α (SMA-α) protein expression were determined.According to our results, SJ-6 significantly decreased AGEs content, ALP activity, intracellular calcium content, ROS content, Runx2 mRNA and inflammatory factors TNF-α, 1L-6 and 1L-β (P < 0.05) and increased SOD content (P < 0.01), with similar to those of the positive control drug aminoguanidine hydrochloride (AGH).Therefore, we investigated the pharmacological mechanism of compound SJ-6, which was found to significantly inhibit the expression of RAGE, NF-κB, NoX-1, PKC, Akt, p-p38 and other essential signaling proteins in the calcified cell model (P < 0.01) and increas the expression of smooth actin SMA-α (P < 0.01).SJ-6 inhibits vascular calcification by inhibiting oxidative stress and the expression of AGEs/RAGE, Akt/PKC and NF-κB signaling pathways, suggesting that it may be a novel drug for the treatment of vascular calcification.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*

Objective To study the clinic significance of allergen serum immunoglobulin E (IgE) detection for the flying personnel with allergic rhinitis.Methods One hundred and twentyeight flying personnel with clinically suspected allergic rhinitis were drawn 2 ml venous blood.Serum tIgE (total IgE) and 14 allergen sIgE (specific IgE) including 7 aspiration allergens and 7 food allergens were detected with antibody kit.Strong positive reaction rates of the flying personnel with aspiration allergens and food allergens were compared as well as the correlation of serum tIgE and positive reaction rate of allergen sIgE was analyzed.Results Positive reaction rate of tIgE in 128 flying personnel with allergic rhinitis was 85.9 ％ (110/128) and positive reaction rate of sIgE was 91.4％ (117/128).The top 3 positive reaction rates of aspiration allergens were dust mite (66.4％),tree combination (32.8％) and house dust (23.4％).The top 3 positive reaction rates of food allergens were fruit combination (mango/pineapple/apple/peach/strawberry) (18.0％),seafood combination (shrimp/crab/scallop) (16.4％) and fish combination (ling/trout/weever) (13.3％).Positive response rate of the flying personnel with both aspiration and food allergens was 12.5 ％ (16/128).The aspiration allergens mainly reflected as strong positive reaction while the food allergens mainly expressed as weakly positive reaction.The strong positive reaction showed significance between aspiration and food allergens.(x2=16.881,P＜0.05).The strong positive reaction of allergen serum had the positive correlation to tIgE value (r=0.517,P＜0.01).Conclusions The allergen serum IgE detection have shown its objective,accurate and noninvasive advantages and are with less age,disease,medication,manipulation and other external limitations.The test results can be quantitatively or semi-quantitatively expressed and can determine tIgE level within the detection.So it has certain clinical significance on diagnosis,treatment,evaluation and prevention for the flying personnel with allergic rhinitis.

Objective To study the clinic significance of allergen serum immunoglobulin E (IgE) detection for the flying personnel with allergic rhinitis.Methods One hundred and twentyeight flying personnel with clinically suspected allergic rhinitis were drawn 2 ml venous blood.Serum tIgE (total IgE) and 14 allergen sIgE (specific IgE) including 7 aspiration allergens and 7 food allergens were detected with antibody kit.Strong positive reaction rates of the flying personnel with aspiration allergens and food allergens were compared as well as the correlation of serum tIgE and positive reaction rate of allergen sIgE was analyzed.Results Positive reaction rate of tIgE in 128 flying personnel with allergic rhinitis was 85.9 ％ (110/128) and positive reaction rate of sIgE was 91.4％ (117/128).The top 3 positive reaction rates of aspiration allergens were dust mite (66.4％),tree combination (32.8％) and house dust (23.4％).The top 3 positive reaction rates of food allergens were fruit combination (mango/pineapple/apple/peach/strawberry) (18.0％),seafood combination (shrimp/crab/scallop) (16.4％) and fish combination (ling/trout/weever) (13.3％).Positive response rate of the flying personnel with both aspiration and food allergens was 12.5 ％ (16/128).The aspiration allergens mainly reflected as strong positive reaction while the food allergens mainly expressed as weakly positive reaction.The strong positive reaction showed significance between aspiration and food allergens.(x2=16.881,P＜0.05).The strong positive reaction of allergen serum had the positive correlation to tIgE value (r=0.517,P＜0.01).Conclusions The allergen serum IgE detection have shown its objective,accurate and noninvasive advantages and are with less age,disease,medication,manipulation and other external limitations.The test results can be quantitatively or semi-quantitatively expressed and can determine tIgE level within the detection.So it has certain clinical significance on diagnosis,treatment,evaluation and prevention for the flying personnel with allergic rhinitis.