OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Conducting local tolerance testing on parentaral drugs is of great significance for evaluating the clinical medication risks of drugs.Although relevant domestic and international guidelines provide detailed instructions on how to conduct local tolerance testing,it was found that some products still provide non-standard application materials,which affects the efficiency of drug development.This article summarizes the information on domestic and international guidance related to the local tolerance testing and elaborates on common problems based on specific application cases,with the aim of of providing reference for related work.

Objective To explore the incidence of long CO VID symptoms in patients infected with Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods According to the inclusion and exclu-sion criteria of literatures,relevant studies without language restrictions published up to 2024 were retrieved from both Chinese and English databases.The Chinese databases were China National Knowledge Infrastructure(CNKI),Wanfang Database,and VIP databases,and the foreign databases were PubMed,Embase,and Web of Science.Three-step screening was used to select literatures,and Stata 17.0 software was used for analysis.Results The incidence of at least one sequelae in patients infected with Omicron variant was 29.62％.The most common symptoms included fatigue(19.10％),joint or muscle pain(11.06％),memory loss(9.71％),brain fog(8.80％),cough(8.42％),headache(7.26％),and sore throat(6.68％).Subgroup analysis results showed that with the extension of follow-up(3 months vs 6 months),the incidence of smell or taste changes was significantly re-duced(7.22％vs 0.78％).The higher the proportion of women(＜50％vs 50％-65％vs＞65％),the higher the incidence of joint or muscle pain(1.09％vs 4.62％vs 19.53％);the greater the median age(≥45 years vs＜45 years),the higher the incidence of chest pain or chest distress(0.90％vs 3.86％),all with statistically significant differences(all P＜0.05).Conclusion Incidence of long COVID in Omicron-infected patients is high and can cause various symptoms.Follow-up time,median age and gender proportion have significant impacts on the incidence of some symptoms.

Objective To investigate the control status of bronchial asthma(referred to as"asthma")in school-age children with normal pulmonary ventilation function and the occurrence of acute attacks within 1 year of follow-up.Methods A retrospective analysis was conducted on clinical data of 327 children aged 6-14 years with bronchial asthma and normal pulmonary ventilation function from April to September 2021.Based on the measured value of one second rate(FEV1/FVC),the children were divided into the ≥80％group(267 cases)and the＜80％group(60 cases).The pulmonary ventilation function,asthma control level,and occurrence of acute attacks within 1 year were compared between the two groups.Results The baseline pulmonary ventilation function in the＜80％group was lower than that in the ≥80％group,and the proportion of small airway dysfunction was higher than that in the ≥80％group(P＜0.05).After standardized treatment for 1 year,the small airway function indices in the＜80％group improved but remained lower than those in the ≥80％group(P＜0.05).The rate of incomplete asthma control at baseline was 34.6％(113/327),and the asthma control level in the＜80％group was lower than that in the ≥80％group(P＜0.05).After standardized treatment for 1 year,the asthma control level in the＜80％group remained lower than that in the ≥80％group,and the proportion of acute asthma attacks was higher than that in the ≥80％group(P＜0.05).Conclusions Approximately one-third of school-age children with asthma still have incomplete asthma control when their pulmonary ventilation function is normal.Among them,children with measured FEV1/FVC＜80％have an increased risk of acute asthma attacks and require close follow-up and strengthened asthma management.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Coronary artery disease(CAD) caused by atherosclerosis(AS) is a major contributor to the global burden of disease. The pathogenesis of CAD is complex, and the subset and function of cardiac macrophages are important factors affecting the occurrence and development of AS and the prognosis of CAD. Recent studies have shown that some traditional Chinese medicine(TCM) formulas and active ingredients can regulate macrophage subsets involved in the inflammation, injury, and repair process of CAD. This paper summarized the significant role of macrophages in AS and myocardial infarction. Based on the plasticity of macrophages, this paper elaborated that traditional Chinese medicine prevented and attenuated AS by regulating macrophage subsets, reducing the level of inflammatory factors, and promoting macrophage autophagy.Traditional Chinese medicine participated in the cardiac repair process after myocardial infarction by accelerating the recruitment of M2 macrophages, inhibiting the polarization of M1 macrophages mediated by glycolysis, inhibiting M1 macrophage-mediated cardiac nerve remodeling, and promoting M2 macrophage-mediated angiogenesis. In addition, in vitro studies on the regulation of macrophage subsets by the active ingredients of traditional Chinese medicine were also reviewed. It was pointed out that nuclear factor kappa B(NF-κB), adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt), chemokine(C-C motif) ligand 2/C-C chemokine receptor type 2(CCL2/CCR2) were the key targets and pathways for the regulation of macrophages by TCM.
Humans ; Phosphatidylinositol 3-Kinases ; Medicine, Chinese Traditional ; Myocardial Infarction ; Coronary Artery Disease ; Inflammation/drug therapy* ; AMP-Activated Protein Kinases ; Macrophages ; NF-kappa B

Objective To compare the diagnostic performance of PI-RADS v2.1 and PI-RADS v2 in the detection of clinically significant prostate cancer(csPCa) by Meta-analysis. Methods The major biomedical databases were searched (CNKI, CBM, Medline, and Embase) with the keywords "PIRADS v2.1" or "PI-RADS v2.1". The Quality Assessment of Diagnostic Accuracy Studies Tool v2 (QUADAS-2) was used to evaluate literature quality. Meta-analysis was performed using STATA17.0 and ReMan5.4 software. Forest plots were used to represent the sensitivity and specificity of PI-RADS v2.1 and PI-RADS v2 for each study. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were combined, and diagnostic performance was evaluated using asummary receiver operating characteristic curve (SROC). Subgroup analysis was performed on three covariables: tumor location, threshold, and the nationality of authors. Results A total of 12 studies were included, involving 3 158 patients and 3 243 lesions. Forall zones and the whole gland, PI-RADS v2.1 had a larger area under the SROC curve (AUC) for csPCa performance, compared with PI-RADS v2. Subgroup analysis: PI-RADS v2.1 also had a larger area under the SROC (AUC) to detect transitional zone csPCa. Different diagnostic thresholds: when a score of 4 was used for the threshold, PI-RADS v2.1 had the maximum area under SROC (AUC) for csPCa performance detection. Author nationality: Researches of PI-RADS v2.1 in Chinese authors had the largest area under the SROC (AUC) in detecting csPCa performance. Conclusion Compared with PI-RADS v2, the diagnostic performance of PI-RADS v2.1 in detecting csPCa is not obviously improved and overall specificity is still low.

This review aims to sum up how Non-coding RNAs (ncRNAs) regulate the development of periodontitis and provides a new perspective for understanding the pathogenesis of periodontitis. We explored the ncRNA's dual role in the development of periodontitis by summarizing evidence from previous in vivo and in vitro studies as well as clinical samples. In our review, the downregulation of 18 miRNAs, 22 lncRNAs and 10 circRNAs demonstrates protective roles in periodontitis. In contrast, the expression of other 11 miRNAs, 7 lncRNAs and 6 circRNAs are upregulated in periodontitis, which promote the progression of periodontitis. These dysregulated ncRNAs exert their protective or destructive roles by mainly influencing cell proliferation, differentiation and apoptosis via cross-talking with various molecules or signaling pathways. Our findings suggested which and how ncRNAs promote or delay the progression of periodontitis, which may greatly contribute to diagnose and therapy development of periodontitis based on ncRNAs in the future.
Humans ; RNA, Long Noncoding/genetics* ; RNA, Circular ; MicroRNAs ; Periodontitis/genetics* ; Apoptosis