To investigate the efficacy of hetrombopag for thrombocytopenia in patients with idiopathic multicentric Castleman disease(iMCD)-TAFRO(thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly)subtype.

ObjectiveTo explore the impact of subjective vertical perception impairment after stroke on visuospatial cognition, balance, walking and activities of daily living, to investigate the mediating role of visuospatial cognition and lateropulsion. MethodsFrom February to December, 2023, 96 stroke patients were selected from the Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University. They were divided into vertical perception impairment group (n = 53) and non-vertical perception impairment group (n = 43). They were assessed with National Institutes of Health Stroke Scale (NIHSS), the Scale for Contraversive Pushing (SCP), Burke Lateropulsion Scale (BLS), Line Bisection Test (LBT), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Subjective Visual Vertical (SVV), Berg Balance Scale (BBS), Holden Functional Ambulation Categories (FAC) and Barthel Index (BI). ResultsScores of SVV orientation, SVV uncertainty, NIHSS, SCT, SCP, BLS, BBS, FAC and BI were worse in the vertical perception impairment group than in the non-vertical perception impairment group (|t| > 2.414, Z = -3.481, P < 0.05). Scores of SVV were correlated with SCT, BLS and BBS (|r| ≥ 0.273, P < 0.05). After controlling for age and gender, SVV orientation score did not directly impact BBS score (β = -0.011, P = 0.920). However, it exerted a partial mediating effect through BLS (effect = -0.173, 95%CI -0.278 to -0.076) and a chain-mediated effect through SCT and BLS (effect = -0.073, 95%CI -0.137 to -0.027), impacting BBS score. ConclusionSubjective vertical perception impairment results in poorer visuospatial cognition, balance, walking and activities of daily living in stroke patients. This influence on balance function is mediated through the mediating effects of visuospatial cognition and lateropulsion.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diag-nosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using polyadenine(polyA)-mediated fluorescent spherical nucleic acid(FSNA)for miRNA analysis based on strand displacement reactions on gold nanoparticle(AuNP)surfaces and electrokinetic signal amplification(ESA)on a microfluidic chip.In this FSNA,polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au.The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA,resulting in fluores-cence quenching of FSNA probes induced by AuNP-based resonance energy transfer.Reporter DNA was replaced in the presence of target miRNA,leading to the recovery of reporter-DNA fluorescence.Sub-sequently,reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA.Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM.This method could also be used to detect miRNA-21 in human serum and urine samples,with re-coveries of 104.0％-113.3％and 104.9％-108.0％,respectively.Furthermore,we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs(miRNA-21,miRNA-141,and miRNA-375),which increased the detection efficiency.Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.

Idiopathic multicentric Castleman disease(iMCD) is a rare and highly heterogeneous lymphoproliferative disorder, which represents a distinct subtype of Castleman disease(CD). In 2018, it was included in the China's First List of Rare Disease issued by the National Health Commission of the People's Republic of China. The prognosis of iMCD patients remains poor, with a previously reported 5-year overall survival rate ranging from only 51% to 77%. This highlights an urgent need for effective treatments. The successful application of interleukin-6(IL-6) targeted therapies represents a major breakthrough in the treatment of iMCD. However, a considerable number of patients still fail to benefit from IL-6 targeted treatments. With in-depth research into the molecular mechanisms of the disease, non-IL-6 targeted therapies have gained increasing attention. Conventional regimens targeting plasma cell disorders or lymphoma-like conditions such as anti-CD20 monoclonal antibodies, bortezomib-cyclophosphamide-dexamethasone, and thalidomide-cyclophos-phamide-prednisone, as well as emerging therapies, including mTOR pathway inhibitors, Bruton's tyrosine kinase inhibitors, JAK-STAT pathway inhibitors, and tumor necrosis factor inhibitors, have shown promising efficacy in iMCD treatment.These developments contribute to the progress in iMCD therapy.This article will elaborate on the therapeutic progress of iMCD, with the aim of providing reference for clinical practice.

Objective:To investigate the pathological changes of JNET classification of colorectal tumors.Methods:Data of patients with colorectal neoplasms who underwent narrow-band imaging combined with magnifying endoscopy, and whose postoperative pathological specimens were obtained at the endoscopy center of the Affiliated Hospital of Guizhou Medical University from January 2015 to June 2018 were analyzed retrospectively. The endoscopic JNET diagnosis and pathological features (surface pit epithelial exfoliation, surface mucosal necrosis structure, surface mucosal ethmoid reticular structure, fibrous tissue reactive hyperplasia, mucosa muscle without residual and carcinomatous interstitial reaction) were analyzed.Results:A total of 81 patients with colorectal neoplasms (diameter >1.5 cm) were enrolled with 74 cases receiving endoscopic treatment and seven cases receiving surgical treatment. The frequency of surface mucosal sieve reticular structure in type 3 of JNET (20.00%) was lower than that in type 2B (42.86%), which was in turn higher than that in type 2A (2.78%), with significant differences ( P<0.05). The frequencies of fibrous tissue reactive proliferation, no residual mucosal muscles, and carcinomatous interstitial reaction in type 2A and 2B were lower than that of type 3, with significant differences (all P<0.05). There were significant differences in the consistency group and inconsistency group of JNET classification and pathological diagnosis in surface pit epithelial exfoliation and surface mucosal necrosis (all P<0.05). Conclusion:Type 2B of JNET classification indicates that the pathological features may be the surface mucosal reticular structure; type 3 indicates reactive hyperplasia of fibrous tissue, no residual mucosal muscles and cancerous interstitial reaction. The exfoliation of the surface pit epithelium and the necrosis of the surface mucosa may be the pathological interference factors affecting the accuracy of JNET classification diagnosis.