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.

This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel (abpaclitaxel) and anlotinib for ovarian cancer. In this study, 44 patients diagnosed with platinum-resistant ovarian cancer were enrolled. Patients received ab-paclitaxel along with anlotinib until disease progression or intolerable toxicity. Efficacy was assessed according to RECIST 1.1 criteria or Rustin's criteria. The primary endpoint was the investigator-evaluated objective response rate (ORR). 44 patients were enrolled between January 2021 and March 2023 with a median age of 49 years. Twenty-nine had measurable lesions and 15 had non-measurable lesions. Overall, the investigator-evaluated ORR was 56.8% (25/44; 95% CI 0.411-0.713) in intention-to-treat population and 58.1% (25/43; 95% CI 0.422-0.726) in per-protocol population. The median progression-free survival was 9.8 months, and the median duration of response was 7.4 months. For safety, grade 3/4 adverse events (AEs) included leukopenia, gum pain, hypertension, and hand-foot syndrome. The response rates were 55.0% (11/20) in patients with previous use of antiangiogenic reagents and who had previous use of PARP inhibitors. The combination of ab-paclitaxel and anlotinib showed promising anti-tumor activity and a manageable safety profile in platinum-resistant ovarian cancer. Patients with previous use of antiangiogenic drugs or PARP inhibitors still benefited from this protocol.
Humans ; Female ; Middle Aged ; Indoles/therapeutic use* ; Quinolines/therapeutic use* ; Carcinoma, Ovarian Epithelial/drug therapy* ; Adult ; Ovarian Neoplasms/drug therapy* ; Prospective Studies ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Aged ; Drug Resistance, Neoplasm ; Albumin-Bound Paclitaxel/therapeutic use* ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival ; Paclitaxel/administration & dosage* ; Treatment Outcome

A 72-year-old female patient was admitted to the emergency department of Qintang District People′s Hospital of Guigang City in August 2023 due to chills and fever, abdominal distension and pain, diarrhea, cough and shortness of breath for 1 day. She had a history of chronic obstructive and pulmonary heart disease, stage Ⅲ hypertension, and ceftazidime allergy. Clinical diagnosis of acute bacterial infection of chronic obstructive pneumonia was made and levofloxacin combined with piperacillin/tazobactam were given as symptomatic treatment. The blood culture reported Campylobacter fetus after four days, and the patient was cured and discharged after seven days with negative blood culture. The morphology and mass spectrometry identification of the strain were consistent with the definition of Campylobacter fetus. Whole genome sequencing predicted the multi-site sequence type as Campylobacter fetus subsp. fetus( Cff) ST20, carrying the tetracycline resistance gene tet (O/M/O), 18 flagella genes (including rpoN gene from Campylobacter jejuni. these genes were not found in the other two Campylobacter fetus subspecies), and six virulence genes (including like-typhoidal toxin and typhoid toxin genes). The pathogen has the ecological characteristics of parasitic farmed animal colonization and the biological characteristics of high mobility and virulence. These attributes facilitated its entry into the bloodstream via the fecal-oral route, leading to invasive infections.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4％)patients were DSA positive,including 7(46.7％)cases of strong positive,3(20.0％)cases of moderate positive,and 5(33.3％)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95％CI:1.505～57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100％rate of successful transplantation,and 6 received single desensitization,with 4(66.7％)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

OBJECTIVES: Currently, it is difficult to assess the expression status of hormone receptor (HR) in breast malignant tumors with human epidermal growth factor receptor 2 (HER-2)-positive in the early preoperative stage, and it is difficult to predict whether it is non-invasively. This study aims to explore the value of MRI on the different HR expression status (HR⁺/HR^-) in HER-2 positive breast cancer. METHODS: Thirty patients with HR+ HER-2-positive breast cancer (HR+ group) and 23 patients with HR-HER-2-positive breast cancer (HR- group) from the First Hospital of Hunan University of Traditional Chinese Medicine between January 7, 2015 and November 26, 2021 were selected as subjects, and all the patients were examined by MRI and all were confirmed by surgery or pathological biopsy puncture. The immunohistochemical staining results were used as the gold standard to analyze the basic clinical conditions, peri-lesion conditions and MRI sign characteristics in the 2 groups. RESULTS: There were all significant differences in terms of mass margins, internal reinforcement features, and apparent diffusion coefficient (ADC) values between the HR+ group and the HR- group (all P<0.05). The logistic multivariate regression model showed that: when the lesion presented as a mass-type breast cancer on MRI, the internal enhancement features of the lesion were an independent predictor for differentiation in the 2 types of breast cancer [odds ratio (OR)=5.95, 95% CI: 1.223 to 28.951, P<0.05], and the mass margin (OR=0.386, 95% CI: 0.137 to 1.082, P>0.05) and ADC value (OR=0.234, 95% CI: 0.001 to 105.293, P>0.05) were not the independent predictors in distinguishing the 2 types of breast cancer. CONCLUSIONS Multiparametric MRI has good diagnostic value for HR expression status in HER-2-positive breast cancer. Combined logistic regression analysis to construct a predictive model may be helpful to the identical diagnosis.
Humans ; Female ; Breast Neoplasms/surgery* ; Magnetic Resonance Imaging/methods* ; Diffusion Magnetic Resonance Imaging/methods* ; Breast ; Magnetic Resonance Spectroscopy ; Retrospective Studies

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Ischemic stroke is an acute and serious cerebrovascular accident.Neurodegenerative disorders are characterized by progressive degeneration of neu-rons in the central nervous system(CNS),resulting in severe disability and death.Myelin is essential for the health and function of neuronal axons.Oligodendrocytes,the myelinating cells of CNS,are vulnerable to ischemia and neurodegenerative disorders.G protein-coupled receptor 17(GPR17)is a dual receptor activated by uracil nucleotides/cysteinyl leukotrienes(CysLTs).Abnormal GPR17 activation contributes to oligodendrocyte dysfunc-tion and axonal damage.Gelosa et al.reported that CysLT1 receptor antagonist montelukast increased the recruitment and proliferation of oligodendrocyte precursor cells(OPCs)at the acute phase after ischemic stroke.Similarly,a study showed that montelukast stimulated neural progenitor proliferation and hippocampal neuro-genesis of aged rats through inhibition of GPR17.These results were supported by several studies on neurode-generative diseases.The authors showed that pharmaco-logical blockade of GPR17 with CysLT1 or CysLT2 recep-tor antagonists(montelukast or HAMI3379)improved oli-godendrocyte function and fiber connectivity,highlighting GPR17 as a potential therapeutic target in oligodendro-cyte protection and remyelination.Recently,growing evi-dence has revealed a significant interaction between mi-croglia and oligodendrocytes in CNS injury and disease.It was reported that M2 microglia promoted,while M1 microglia inhibited oligodendrogenesis,OPCs maturation and remyelination.Microglia-mediated neuroinflamma-tion,considered as an important pathological event,neg-atively affected OPCs fate and function in experimental neurological disorders.This was further corroborated by later studies.It was recently reported that montelukast enhanced OPCs differentiation and maturation by upreg-ulating the number of M2 microglia at chronic phase of brain ischemia.In line with the above results,inhibition of microglial inflammation by montelukast was shown to be responsible for neurite outgrowth.Although the exact mechanisms were not fully clarified,these results indi-cate that montelukast may indirectly promote OPCs dif-ferentiation and remyelination by a microglia-dependent manner.It has been widely accepted that CysLT1,CysLT2 and GPR17 receptors are localized in various cell types and their expression are upregulated after brain damage.Therefore,it is likely that CysLT receptor antagonists confer neuroprotection by targeting different receptors and multiple cell functions.Many studies have reported that CysLT receptor antagonists promote protec-tion of oligodendrocytes by inhibiting GPR17.Moreover,they may improve OPCs differentiation and neuronal sur-vival by regulating CysLTs-mediated microglial activation.Altogether,these data open novel perspectives in the treatment of cerebral ischemia and neurodegenerative diseases.

Objective To explore the relationship between non-high density lipoprotein cholesterol(non-HDL-C)level and leptomeningeal collateral circulation in patients with acute middle cerebral artery occlusion.Methods A total of 85 patients with first-onset acute cerebral infarction with middle cerebral artery M1 segment occlusion were enrolled.According to the results of DSA,LMC circulation was assessed by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Circulation Assess-ment System.All patients were assigned to better LMC circulation group(score 2～4,n = 30)and worse LMC circulation group(score 0～1,n = 55),and the levels of non-HDL-C were compared between the two groups.Results The levels of LDL-C and non-HDL-C in worse LMC circulation group were significantly higher than those of the better LMC circulation group(P = 0.026,P = 0.010).non-HDL-C was an independent risk factor for the worse LMC circulation(OR = 3.019,95%CI:1.053～8.658,P = 0.04).LMC circulatory score of patients was negatively correlated with the levels of non-HDL-C level(r =-0.228,P = 0.036).The AUC of non-HDL-C predicted for the worse LMC circulation was 0.638(95%CI:0.521～0.755,P = 0.036).Conclusions non-HDL-C in patients with acute cerebral infarction was significantly related to worse LMC circulation,and was a risk factor for worse LMC circulation.It is suggested that the higher expression of non-HDL-C could be used to predict worse LMC circulation as a serological indicator.