High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective:To investigate the effect of blood lipids and statins use on the outcome of acute ischemic stroke (AIS) patients with cerebral microbleeds (CMBs).Methods:Consecutive AIS patients with CMBs hospitalized at the First People's Hospital of Taicang, Jiangsu Province from July 2023 to June 2024 were included retrospectively. At 3 months after onset, the modified Rankin Scale was used for outcome assessment. 0-2 was defined as good outcome and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to identify independent influencing factors for poor outcome. Results:A total of 110 AIS patients with CMBs were enrolled, including 72 males (65.5%), aged 68.04±3.12 years. Thirty patients (27.3%) had poor outcome. Univariate analysis showed that age, baseline National Institutes of Health Stroke Scale (NIHSS) score, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and the proportion of patients with hypertension and diabetes in poor outcome group were significantly higher than those in good outcome group, while baseline high-density lipoprotein cholesterol and the proportion of patients using statins before onset were significantly lower than those in good outcome group ( P<0.05). Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.309, 95% confidence interval [ CI] 1.007-1.702; P=0.044), the baseline NIHSS score ( OR 1.541, 95% CI 1.143-2.078; P=0.005) and high triglycerides ( OR 5.150, 95% CI 2.150-8.717; P=0.023) were the independent risk factors for poor outcome, while high high-density lipoprotein cholesterol ( OR 0.001, 95% CI 0.001-0.034; P<0.001) and statins use ( OR 0.231, 95% CI 0.046-0.558; P=0.019) were the independent protective factors for good outcome. Conclusions:Blood lipid and statins use are independent influencing factors for the outcome of AIS patients with CMBs. The use of statins before onset is associated with a lower risk of poor outcome in AIS patients with CMBs.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

Objective:To explore the distribution characteristics of Mycoplasma pneumoniae (MP) antibody detection data in hospital, provide data reference for the prevention and control of MP infections.Methods:A single-center retrospective study was conducted on 20 639 patients with suspected Mycoplasma pneumoniae (MP) infection from March 2017 to February 2024 at the outpatient, emergency, and inpatient departments of Peking University Third Hospital. The age range was from 0 to 105 years, with 11 286 males and 9 353 females. The passive agglutination method was used to detect MP antibodies in patient serum, and SPSS 22.0 statistical software was used for statistical analysis. The χ2 test was used to analyze the differences in positive rates of MP antibodies among different genders, age groups, seasons, years, and antibody titers. The trend χ2 test was used to analyze the trend of detection rates with age changes. Results:Among the 20 639 patients, the positive rate of MP antibodies was 23.19%(4 786/20 639), with a higher positive rate in females was 27.16%(2 540/9 353) compared to males (19.90%, 2 246/11 286; χ2=151.191, P<0.01). The positive rate in children was 37.13%(2 731/7 356)significantly higher than in adults(15.47%, 2 055/13 283; χ2=1 246.433, P<0.01). The 6 to <12 year age group (63.11%, 1 223/1 938) had the highest positive rate of MP antibodies, followed by 12 to <18 year old group (56.78%, 385/678). The positive rate of MP antibodies increased with age from 0 to 12 years old but gradually decreased after 12 to <18 years old ( χ2=3 848.393, P trend<0.01). The annual MP antibody positivity rates from 2017 to 2023 were 26.92%, 29.23%, 27.46%, 18.43%, 17.16%, 11.89%, and 23.72%, respectively, with statistically significant differences among the years ( χ2=387.519, P<0.01). The MP antibody positive rate was high in autumn over the course of 7 years ( χ2=242.560, P<0.01). The positive rates of MP antibodies for the years 2017-2019, 2020-2022, and 2023-2024 are (28.00%, 16.60%, 21.84%), respectively, with statistically significant differences among the three periods( χ2=295.845, P<0.01).The monthly positive rates of MP antibody in different years were (5.63% to 43.11%). In the MP antibody titer, qualitative testing was conducted on 4 563 patients and 16 076 patients had a semi-quantitative MP antibody titer of ≥1∶160 with a positive rate of 16.03%(2 577/16 076). Among the proportion of children with high titers of MP antibodies ≥1∶1 280 was 11.11%(798/7 182). Conclusion:The positive rates of MP antibodies in hospital in the Beijing area vary among different genders, ages, and seasons, with a higher incidence in autumn, mainly among children and adolescents.

A case of 75-year-old male patient was admitted to the Second Affiliated Hospital of Harbin Medical University on June ,2024 complaining 'repeated cough for half a year', accompanied by night fever, night sweats, fatigue, weight loss. He was initially diagnosed as diffuse large B-cell lymphoma through chest CT and bronchoscopic biopsy, then confirmed as diffuse large B-cell lymphoma with MYD88 genetic aberration with bone marrow inconsistent involvement by PET-CT, bone marrow biopsy, immunohistochemistry(IHC),FISH and other tests. The R-CHOP was given as first-line regimen treatment immediately, but the patient appeared allergyic to Rituximab and Zuberitamab sequencially, therefore we change the plan to CDOP for continued chemotherapy and discharged after remission. In his regular admission, we give G-CHOP regimen for chemotherapy, no adverse reactions were found.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective To systematically review the efficacy and safety of reduced versus standard doses of CDK4/6 inhibitors in patients with HR+/HER2-advanced breast cancer.Methods PubMed,Web of Science,Cochrane Library,Embase,CNKI,WanFang Data,VIP,databases were electronically searched to collect randomized controlled trials(RCTs)on HR+/HER2-advanced breast cancer patients treated with reduction of CDK4/6 inhibitor dose and standard dose from inception to April 1,2025.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.1 software.Results A total of 14 RCTs involving 4,958 patients were included.The results of Meta-analysis showed that there was no statistically significant difference in PFS[HR=1.01,95％CI(0.92,1.11),P=0.81]and OS[HR=0.78,95％CI(0.52,1.18),P=0.25]in the dose-reduced group and the standard dose group,while ORR[RR=0.83,95％CI(0.71,0.96),P=0.01]and incidence of grade 3 and above neutropenia[RR=0.42,95％CI(0.21,0.85),P=0.02]in the dose-reduced group were significantly better than those in the standard dose group.Conclusions Current evidence shows that the dose reduction of CDK4/6 inhibitors can considerably reduce the incidence of grade 3 and above neutropenia without affecting PFS and OS.

Objective To systematically review the efficacy and safety of reduced versus standard doses of CDK4/6 inhibitors in patients with HR+/HER2-advanced breast cancer.Methods PubMed,Web of Science,Cochrane Library,Embase,CNKI,WanFang Data,VIP,databases were electronically searched to collect randomized controlled trials(RCTs)on HR+/HER2-advanced breast cancer patients treated with reduction of CDK4/6 inhibitor dose and standard dose from inception to April 1,2025.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.1 software.Results A total of 14 RCTs involving 4,958 patients were included.The results of Meta-analysis showed that there was no statistically significant difference in PFS[HR=1.01,95％CI(0.92,1.11),P=0.81]and OS[HR=0.78,95％CI(0.52,1.18),P=0.25]in the dose-reduced group and the standard dose group,while ORR[RR=0.83,95％CI(0.71,0.96),P=0.01]and incidence of grade 3 and above neutropenia[RR=0.42,95％CI(0.21,0.85),P=0.02]in the dose-reduced group were significantly better than those in the standard dose group.Conclusions Current evidence shows that the dose reduction of CDK4/6 inhibitors can considerably reduce the incidence of grade 3 and above neutropenia without affecting PFS and OS.