Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

Objective: To investigate the precise detection methods for weak partial D type 15 and evaluate their implications for blood transfusion safety, along with the development of corresponding strategies. Methods: A combination of serological methods, including the microplate method, indirect antiglobulin tube method, and microcolumn gel card method, was employed to identify RhD-negative and RhD variant samples. RhD-negative samples were screened for the presence of RHD genes using whole-blood direct PCR amplification. Subsequently, RhD variant samples and RhD-negative samples containing RHD genes underwent full-coding-region sequencing of the RHD gene to confirm their genotypes. The genotyping results were further correlated with the serological test findings for comprehensive analysis. Results: Among 615 549 first-time healthy blood donors, 3 401 samples with an RhD-negative phenotype and 156 samples with RhD variant were identified. Of the 3 401 RhD-negative samples, 1 054 were found to harbor RHD genes. Gene sequencing analysis of the 156 RhD variants and the 1 054 serological negative samples revealed that 89 samples contained the RHD 15 (c. 845G>A) allele. Conclusion: The integration of serological testing methods and genotyping technologies for the precise determination of RhD blood type plays a critical role in ensuring the safety and compatibility of blood transfusions.

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Objective To analyze the pattern of group medication in Parkinson's disease cognitive disorders based on data mining.Methods The famous TCM experience and effective clinical treatment of cognitive impairment in the treatment of Parkinson's disease were retrieved in databases of CNKI,Wanfang and Weipu,from the founding of the databases to August 2024.Medication rules were analyzed.Results A total of 60 Chinese prescriptions were included,including 120 traditional Chinese medicines.High-frequency drugs for the treatment of cognitive impairment in Parkinson's disease included Radix Rehmanniae Praeparata,Radix Paeoniae Alba,Rhizoma Gastrodiae Praeparata,Fructus Lycii,Herba Cistanches,Acorus Calamus and others.The flavour of the medicine were mainly sweet,bitter and pungent,the nature of the medicine was mainly warm,cold and calm and the meridians of the medicine were mainly liver,kidney and heart.Radix Rehmanniae Praeparata-Comu Cervi Pantotrichum,Rhizoma Gastrodiae Praeparata-Hooker's Tree,Radix Rehmanniae Praeparata-Cistanches are the commonly used pairs;Lycium barbarum-Cornus officinalis-Radix Rehmanniae Praeparata,Radix Rehmanniae Praeparata-Radix Angelicae Sinensis-Radix Paeoniae Alba were commonly used combination.Cluster analysis yielded 5 broad categories.Conclusion The primary pharmacological agents employed in traditional Chinese medicine to address cognitive impairment associated with Parkinson's disease emphasize the replenishment of essence and nourishing the marrow.These agents are complemented by nootropic substances that facilitate bodily openness,promote liver health,alleviate wind,resolve phlegm,and invigorate blood circulation and meridian pathways,worth of clinical promotion and application.

Objective To examine of Ye Tianshi's approach to managing internal wind through herbal remedies.Methods A comprehensive search was conducted for medical cases pertaining to internal wind,liver wind,dizziness,head wind,deficiency labor,liver fire,insomnia,convulsions,epilepsy,and headache within the Clinical Guidelines in Medical Cases.Statistical analysis of symptom elements,target locations of symptom elements,frequency of Chinese medicinal substances,their properties,and meridian affiliations was performed using Excel.Prescription patterns were further analyzed through association rules and high-frequency drug clustering.Results The study included a total of 167 medical cases,from which 241 symptom elements and 333 target locations were extracted.A total of 183 prescriptions were analyzed,comprising 132 medicinal substances with an overall frequency of 1309 occurrences.The five most frequently used Chinese medicines were Sheng Di Huang,Fu Shen,E Jiao,Fu Ling,and Shu Di Huang.The predominant property observed was cold,followed by warm and neutral;the most common flavor was sweet,succeeded by bitter and warm.The leading meridian affiliations identified were liver,kidney,lung,heart,and spleen.The drug association rule analysis revealed 14 items,while high-frequency drug clustering resulted in 9 distinct categories.Conclusion Ye Tianshi's therapeutic approach to internal wind emphasizes the concept of"yang transforming into internal wind."The core principles of this treatment strategy involve nourishing bodily fluids to mitigate wind,addressing excess conditions in the upper body while rectifying deficiencies in the lower body,and promoting tranquility in the liver and stomach.Additionally,the use of pungent and sweet flavors is employed to facilitate the transformation of wind,to clear the liver and dispel heat,to eliminate wind and resolve phlegm,to tonify qi and enhance defensive qi,and to clear heat in order to soothe the spirit.This methodology seeks to achieve harmony among the organs and meridians while pacifying internal wind.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objective:To investigate the significance of urinary 8-oxo-7, 8-dihydroguanosine(8-oxoGuo)in assessing the short-term prognosis of sepsis in frail elderly patients.Methods:We conducted a cross-sectional study involving 62 frail elderly patients diagnosed with sepsis who were admitted to the Emergency Intensive Care Unit(EICU)at Beijing Hospital between March 2021 and March 2022.Based on their 28-day prognosis, the patients were categorized into two groups: those who died and those who survived.Upon admission, we collected urine samples and clinical data from both groups.We employed isotope dilution high-performance liquid chromatography-mass spectrometry to measure the levels of the RNA oxidation marker 8-oxoGuo in the urine.Results:A total of 62 frail elderly patients[aged(85.1±6.3)years]diagnosed with sepsis were included in the study, comprising 36 patients in the 28-day mortality group and 26 patients in the survival group.Univariate analysis revealed that the survival group had significantly lower body temperature, blood calcitonin(PCT)levels, sequential organ failure assessment(SOFA)scores, and urinary 8-oxoGuo levels compared to the mortality group.Additionally, the survival group exhibited a higher mean arterial pressure(MAP)than the mortality group, with all differences reaching statistical significance(all P<0.05).Spearman correlation analysis indicated that urinary 8-oxoGuo levels were positively correlated with both PCT and SOFA scores in frail elderly sepsis patients( r=0.426, 0.768, both P<0.05).Furthermore, logistic regression analysis identified urinary 8-oxoGuo and SOFA as independent risk factors for 28-day mortality in this population( OR=1.936, 1.427; P=0.006, 0.002).The area under the receiver operating characteristic curve(AUC)for urinary 8-oxoGuo and SOFA in predicting the 28-day prognosis of frail elderly sepsis patients was 0.761 and 0.741, respectively, both demonstrating statistical significance(both P<0.001). Conclusions:Our findings suggest that urinary 8-oxoGuo possesses strong predictive value for the short-term prognosis of sepsis in this vulnerable population.

Objective:To observe the effects of exercise training on the memory ability of rats with vascular cognitive im-pairment(VCI)and to explore the possible mechanisms of action.Method:Rat models of VCI were constructed by permanently ligating bilateral common carotid arteries,and were randomly divided into sham-operated groups(Sham,n=8),exercise-training groups(VCI+Ex,n=8),and control groups(VCI,n=8)according to the randomized numerical table method.The exercise training group started moderate-intensity aerobic exercise training on a small animal treadmill at 48 hours postoperatively,and the intensity of the exercise was increased day by day(5m/min—11m/min)in the first week,and was per-formed at a constant speed of 11m/min for 30 min per day,5 days per week in the second to fourth weeks.Rats in the sham-operated group and the control group were placed in the small animal treadmill at the same time points,but not turned on,for 30 min per day,5 days per week for 4 weeks.For the rest of the time,rats in each group were put back into the rearing cages and were free to eat,drink and move around.After completing the above experiments,the memory ability of rats in each group was evaluated by Novel Object Recognition(NOR)and Y-maze experiments;then the rats were euthanized by overdose anesthesia,and the hip-pocampal tissues were isolated and extracted from the brain.The distribution of N-methyl-d-aspartate receptor(NMDAR)and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)in the hippocampal re-gion was observed by immunofluorescence staining,and the expression levels of PlexinA4 and neuropilin-2 in the hippocampal region were detected by Western Blot.Result:In the Y-maze experiment,rats in the VCI+Ex group explored the novel arm more frequently than the VCI group,as well as explored for a longer period of time than the VCI group,with significant differences(P<0.05,P<0.001);in the NOR experiment,the cognitive index of novelty of rats in the VCI+Ex group was significantly higher than that of rats in the VCI group,and the difference was significant(P<0.001).Immunoflu-orescence results showed that compared with the VCI group,the expression levels of NMDAR,PlexinA4,and neuropilin-2 in the hippocampal region of the VCI+Ex group were significantly higher(P<0.01,P<0.05,P<0.05,respectively),while there was a tendency for the expression of AMPAR and the ratio of NMDAR/AM-PAR to be elevated.Western Blot results showed that PlexinA4 expression in the hippocampus of VCI+Ex rats was higher than that of the VCI group,and the results were significantly different(P<0.05).Conclusion:Exercise training can improve the memory ability of VCI rats,and the possible mechanism is to promote the expression of NMDAR,PlexinA4 and neuropilin-2 in the hippocampus,which in turn enhances the synaptic plasticity in the hippocampus.

Bipolar disorder in children, a serious mental illness, often leads to significant functional impairment. Bipolar disorder onset in children is rare and is difficult to diagnose correctly due to the atypical clinical manifestations. Risperidone, as a second-generation antipsychotic, shows satisfied efficacy in children with bipolar disorder with dual effects on mood stabilization and psychotic symptom control. However, the long-term efficacy and safety of risperidone for the treatment of children with bipolar disorder remains unknown. This paper reports a 5-year-old child with bipolar disorder who was treated with low-dose risperidone and followed up for 4 years. The child showed significant emotional stabilization and behavioral improvement at the beginning of treatment. No serious side effects occurred during long-term follow-up. This paper detailly describes the clinical manifestations and diagnostic process of bipolar disorder onset in children in aspects of detailed clinical observation and evaluation. It summarizes the efficacy and safety of risperidone in the treatment of pediatric bipolar disorder to provide valuable experience for clinicians.