The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Objective To investigate the effect of Mysm1 on the differentiation of neural stem cells(NSCs)into astrocytes and the possible mechanism.Methods NSCs were prepared from E12.5 cortices of wild-type C57BL/6 mice,cultured in vitro and induced to differentiate into astrocytes.Immunofluorescence staining,real-time quantitative PCR and Western blot assay were used to detect the expressions of Mysm1 during the differentiation of NSCs into astrocytes in vitro.Lentivirus was used to knock down Mysm1 expressions in NSCs before real-time quantitative PCR and Western blot assay were used to detect the knockdown efficiency.Immunofluorescence staining and Western blot assay were used to compare the differentiation of NSCs into astrocytes before and after Mysm1 knockdown in vitro.Transcriptomics was adopted to detect the differential gene after knockdown of Mysm1 in NSCs in vitro.Western blot assay was used to verify the changes of proteins associated with the differential gene.Cut-Tag was used to detect the enrichment of Mysm1 in the promoter region of glial fibrillary acidic protein(GFAP)genes during the differentiation of NSCs into astrocytes in vitro.After overexpression of GFAP following knockdown of Mysm1,immunofluorescence staining and Western blot assay were used to compare the differentiation of NSCs into astrocytes before and after overexpression in vitro.Results The expression of Mysm1 was gradually increased when NSCs were induced to differentiate into astrocytes in vitro.Mysm1 knockdown inhibited the differentiation of NSCs into astrocytes in vitro.Mysm1 affected the differentiation of NSCs into astrocytes by regulating the expression of GFAP.Overexpression of GFAP after Mysm1 knockdown partially rescued the ability of NSCs to differentiate into astrocytes.Conclusion Mysm1 regulates the differentiation of NSCs into astrocytes by epigenetically controlling GFAP transcription.

Objective To analyze the imaging manifestations of malignant transformation of ovarian mature teratoma.Methods The clinical data and CT and MRI imaging findings of four patients confirmed as malignant transformation of ovarian mature teratoma by operation and pathology were analyzed retrospectively.The following imaging features were assessed:size,shape,texture,enhancement degree and pattern,et al.Results Among the four cases,three lesions were located in the left ovary and one in the right ovary.The minimum size and maximum size were 87 mm×80 mm×87 mm and 171 mm×141 mm×215 mm,respectively.All of the lesions showed as round-like or ovoid cystic masses with fat-fluid level(4/4),and floating mixed density or signal masses(2/4).The demonstrated local thickening of the cyst wall(2/4)and/or soft mass growing across the wall(3/4),with significant inhomogeneous enhancement(2/3).Conclusion The malignant transformation of ovarian mature teratoma often presents as a cystic mass with fat-fluid level,and local thickening or soft mass of the cyst wall,with significant enhancement.It should be considered in the elderly patients with abnormal tumor markers and above imaging features.

Objective To investigate the value of unenhanced CT combined with clinical features in predicting adnexal torsion in women with abdominal pain and an adnexal mass. Methods A retrospective selection of patients with abdominal pain and an adnexal mass underwent operation in 2 tertiary hospitals from January 2018 to September 2023. The torsion group (n＝53) and non-torsion group (n＝53) were matched in a 1∶1 ratio. 15 CT signs of adnexal masses were reviewed independently by two radiologists using a double-blind method. The high-risk factors were screened using multivariate logistic regression analysis. The diagnostic values of high-risk factors for adnexal torsion were assessed using receiver operating characteristic (ROC) curves. Results According to the surgical and pathological results, the most common adnexal mass in torsion group was mature cystic teratoma (32.1%), and the most common mass in the non-torsion group was adnexal abscess (20.8%). The age, fever rate, white blood cell count, location of mass, thickened fallopian tube rate, and pelvic effusion rate were not statistically different between the two groups, the nausea and vomiting and remaining CT signs were significant different between the two groups (P＜0.05). Multivariate logistic analysis showed that nausea and vomiting (OR＝4.886), navel sign (OR＝22.733), and whirl sign (OR＝43.462) were independently associated with adnexal torsion (P＜0.05). The area under the curve (AUC) of nausea and vomiting, navel sign, and whirl sign were 0.717, 0.802, and 0.840, respectively; AUC of the combination of all three was 0.877 with 92.45% of sensitivity, 84.91% of specificity, 85.96% of positive predictive value, 91.84% of negative predictive value, and 88.68% of accuracy. Conclusions For women with abdominal pain and an adnexal mass, nausea and vomiting, navel sign, and whirl sign are help of predicting adnexal torsion, and combination value of all three is best.

This paper aims to review treatment delay in first-episode schizophrenia,depression,and bipolar disorder,and to compare related factors of treatment delay in the three first-episode mental disorders.It is found that increased patient responsibility,stigma,lack of disease-related knowledge,lack of access to resources,and insuffi-cient medical support lead to delay treatment,and making patients to have longer course,heavier symptoms,and lower social functions.

With the increase in human activity in plateau and mountainous areas in recent years,high-altitude exposure has become increasingly common.Many patients with underlying diseases are affected by hypobaric hypoxia in plateau environments,which further aggravates disease processes and even leads to cognitive disorders.Periodontitis is a common inflammatory disease that induces periodontal local inflammatory responses and even causes central nervous system inflammation.At high altitudes,the body suffers from decreased immunity and tissue hypoxia,which can promote the occurrence and development of periodontitis and may even increase the risk of periodontitis-induced central nervous system inflammation.As plateau medical research advances,the relationship between periodontitis and central nervous system inflammation in hypobaric hypoxia environments at plateau is attracting more and more attention.This work reviews the progress of research on periodontitis and central nervous system inflammation and discusses the correlation between periodontitis and central nervous system inflammation when exposed to hypobaric hypoxia in plateau environments.

Purpose To analyze the clinical and CT features of hepatoid adenocarcinoma of the stomach.Materials and Methods A total of 38 patients with hepatoid adenocarcinoma of the stomach from September 2012 to April 2023 in the First Affiliated Hospital of Soochow University were retrospectively reviewed,and the clinicopathological data,laboratory examinations,and CT characteristics of the tumor size,morphology,density,border,enhancement pattern,metastasis and invasion were recorded and analyzed.Results Among 38 patients,there were 24 cases with elevated serum alpha-fetoprotein levels and 32 cases with positive immunohistochemical alpha-fetoprotein expression.The maximum diameter was 2.38-11.95 cm in the portal phase,with the median(interquartile range)of 5.200(3.365,7.215)cm.On contrast-enhanced CT scan,there were 23 cases with ulceration,20 cases with internal necrosis,25 cases with peripheral invasion,14 cases with liver metastases,and 5 cases with carcinoma emboli in the portal system.Conclusion Hepatoid adenocarcinoma of the stomach is a rare tumor.Serum alpha-fetoprotein often increases.Size of the tumor is often large on contrast-enhanced CT scan,necrosis,progressive or continuous enhancement,metastasis and invasion of the portal vein are commonly manifested.Understanding these characteristics is helpful to improve the diagnostic level.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective:To investigate the mechanism of trigger point deactivation induced by pressing manipulation in a rat model and to explore its potential regulation of the inflammatory response through the extracellular signal-regulated kinase(ERK)/nuclear factor-κB(NF-κB)pathway. Methods:Fifty male Sprague-Dawley rats were randomly divided into a blank group,a model group,a pressing manipulation group,an ERK agonist group,and a pressing manipulation+ERK agonist group,with 10 rats in each group.Except for the blank group,rats in other groups were used to establish the trigger point rat model using the blunt blow combined with the eccentric exercise method.The pressing manipulation group underwent pressing manipulation intervention at the trigger points.The ERK agonist group received an injection of recombinant human epidermal growth factor via the tail vein.The pressing manipulation+ERK agonist group received interventions from both the pressing manipulation and ERK agonist groups.The pressure pain threshold(PPT)was measured by a mechanical pain threshold detector before and after the intervention.The histological changes were evaluated by hematoxylin-eosin staining after the intervention;the expression levels of ERK,phosphorylated ERK(p-ERK),NF-κB p65(p65),phosphorylated NF-κB p65(p-p65),and phosphorylated NF-κB inhibitor(p-IκB)were detected by Western blotting;the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay. Results:The PPT increased(P<0.05);the inflammatory cells disappeared;the ratios of p-ERK/ERK,p-p65/p65,and p-IκB/β-actin,also the levels of IL-1β,IL-6,and TNF-α all decreased in the pressing manipulation group after the intervention compared with the model group(P<0.05).The PPT decreased significantly(P<0.05),the inflammatory cell presence increased,and the ratios of p-ERK/ERK and p-p65/p65 were elevated(P<0.05);additionally,the levels of IL-6 and TNF-α were significantly higher in the pressing manipulation+ERK agonist group compared with the pressing manipulation group(P<0.05).The PPT was significantly lower(P<0.05),the inflammatory cell count was higher,the ratios of p-ERK/ERK and p-IκB/β-actin and the levels of IL-1β and TNF-α were significantly higher in the ERK agonist group compared with the pressing manipulation+ERK agonist group(P<0.05). Conclusion:Pressing manipulation can effectively alleviate inflammation and pain in trigger point model rats,potentially by inhibiting the ERK/NF-κB signaling pathway.

Objective:To understand the real experience and needs of early exercise rehabilitation in elderly patients with total hip arthroplasty (THA), so as to provide a preliminary basis for intervention research to meet the needs of patients.Methods:Using the purposive sampling method, a total of 12 elderly patients with THA from the First Affiliated Hospital of Naval Medical University from June to September 2021 were selected as the research objects for semi-structured in-depth interviews. Colaizzi 7-step method was used to analyze, summarize and extract the data.Results:The early exercise rehabilitation experience and needs of elderly THA patients could be summarized into four themes such as postoperative exercise being a difficult journey, the need for professional support, the need for external support and internally driven needs and 14 sub themes.Conclusions:There are various problems and needs for early exercise rehabilitation in elderly patients undergoing THA. It is necessary to strengthen communication among doctors, nurses and patients, understand their true feelings and provide personalized care and rehabilitation guidance to improve their treatment experience and enhance their satisfaction.