ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo explore the mechanism of Huoxue Rongluo prescription （HXRLP） in repairing the blood-brain barrier （BBB） after ischemic stroke （IS）. MethodsMale C57BL/6 mice were randomly divided into sham operation （Sham） group， cerebral infarction model （MCAO） group， environmental circadian disruption with cerebral infarction model （ECD-MCAO） group， low-， medium-， and high-dose HXRLP （HXRLP-L， M， and H） groups （8.5， 17， 34 g·kg^-1·d^-1， respectively）， and positive drug butylphthalide （NBP） group （0.23 mL·d^-1）. In the Sham group， only the exposed blood vessels were isolated without suture insertion. In the other groups， the middle cerebral artery occlusion （MCAO） model of mice was prepared. In the ECD-MCAO group， HXRLP groups， and NBP group， the environmental circadian disruption （ECD） model was prepared. The mice in the Sham group， MCAO group， and ECD-MCAO group were given the same volume of soybean oil by gavage， while those in the other groups were given the corresponding drugs by gavage. Samples were collected after 7 consecutive days of administration. The mNSS score was used to evaluate the repair effect of HXRLP on neurological deficits after IS. Hematoxylin-eosin （HE） staining was used to assess the impact of HXRLP on the pathological damage of brain tissue after IS. 2，3，5-Triphenyltetrazolium chloride （TTC） staining and cerebral blood perfusion status were used to evaluate the repair effect of HXRLP on brain tissue damage after IS. Evans blue staining and transmission electron microscopy were used to evaluate the improvement effect of HXRLP on the permeability injury of BBB after IS. Immunofluorescence （IF） staining was used to observe the expression of von Willebrand Factor （vWF）， brain and muscle Arnt-like 1 （Bmal1）， and Occludin in brain tissue. Western blot was used to detect the protein expression of Bmal1， Occludin， tight junction protein （Claudin-5）， vascular endothelial growth factor （VEGF）， and angiopoietins（Ang）， and related analysis was conducted. ResultsCompared with the Sham group， the MCAO group exhibited significantly aggravated neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01） and significantly reduced cerebral blood perfusion （P0.01）. The expression of Bmal1， vWF， vascular endothelial growth factor A （VEGFA）， and Ang in brain tissue was significantly enhanced （P0.01）， while the expression of Occludin and Claudin-5 was significantly weakened （P0.01）. Compared with the MCAO group， the ECD-MCAO group showed significantly aggravated neurological deficits， cerebral infarction volume， and BBB leakage （P0.01）， obviously worsened brain pathological damage （P0.05）， significantly reduced cerebral blood perfusion （P0.01）， and significantly decreased expression of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. Compared with the ECD-MCAO group， the HXRLP groups of all doses presented significantly improved neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01）， significantly increased cerebral blood perfusion （P0.01）， and enhanced expression levels of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. ConclusionHXRLP can regulate the clock protein Bmal1 and promote the expression of VEGFA， Ang， Occludin， and Claudin-5， thereby improving BBB damage after IS.

Objective To explore the mediating role of mobile phone dependency and self-rated health in the relationship between adverse childhood experiences(ACEs)and mental health among young adults.Methods A cross-sectional study was conducted using cluster random sampling among 1 611 young adults(mean age 26.30 years)from a region in Hainan Province.Participants completed the childhood trauma questionnaire(short form),the mobile phone addiction index,the depression-anxiety-stress scale(simplified Chinese version),and a self-rated health questionnaire.Pearson correlation analysis and mediation effect analysis were employed to examine the relationships among ACEs,mobile phone dependency,self-rated health,and mental health.Results ACEs,mobile phone dependency,and self-rated health were all significantly correlated with mental health(all P＜0.01).ACEs had a direct negative effect on mental health(direct effect=0.221,95%confidence interval[CI]0.150-0.293).Furthermore,ACEs exerted indirect effects on mental health through 3 pathways:the independent mediation of mobile phone dependency(indirect effect=0.081,95%CI 0.035-0.130),the independent mediation of self-rated health(indirect effect=0.034,95%CI 0.011-0.062),and the chain mediation of mobile phone dependency and self-rated health(indirect effect=0.009,95%CI 0.004-0.015).Conclusion ACEs have a significant impact on the mental health of young adults,with mobile phone dependency and self-rated health serving as key mediators.Interventions aimed at reducing mobile phone dependency and improving health status may help mitigate the negative impact of childhood trauma on mental health,thereby promoting psychological well-being in this population.

Objective To explore the prognostic value of peripheral blood Th1/Th2 cells and their cyto-kines in elderly patients with diabetic foot ulcer(DFU).Methods A total of 136 elderly DFU patients admit-ted to our hospital from January 2021 to August 2023 were selected as the study objects,and were divided into mild group(grade 0-2,75 cases)and severe group(grade 3-4,61 cases)according to Wagner grading crite-ria.All patients were given symptomatic treatment,and were followed up for 6 months by regular outpatient reexaminations,WeChat and telephone.According to the 6-month prognosis,they were divided into good prog-nosis group(95 cases)and poor prognosis group(41 cases).Baseline data,peripheral blood Th1 cells and their cytokines[interleukin(IL)-2,interferon γ(INF-γ)],Th2 cells and their cytokines(IL-4,IL-10)were com-pared between the two groups.The predictive efficacy of Th1/Th2 cells and their cytokines on poor prognosis of DFU was evaluated.Results Compared with the good prognosis group,the levels of Th1 cells,IL-2 and INF-γ in peripheral blood of the poor prognosis group were higher,and the levels of Th2 cells,IL-4 and IL-10 were lower,with statistical significance(P＜0.05).Compared with mild group,the levels of Th1 cells,IL-2 and INF-γ in peripheral blood of severe group were higher,and the levels of Th2 cells,IL-4 and IL-10 were lower,with statistical significance(P＜0.05).After adjusting for body mass index(BMI),duration of DFU,vascular complications of diabetes mellitus and severity of DFU,Th1 cells,IL-2,INF-γ,Th2 cells,IL-4 and IL-10 were the independent prognoses of DFU(P＜0.05).The AUC of the combination of Th1 cells,IL-2,INF-γ,Th2 cells,IL-4 and IL-10 predicted the poor prognosis of DFU was greater than that predicted by each indi-cator alone.Conclusion Peripheral blood Th1/Th2 cells and their cytokines are closely related to the degree of disease in elderly DFU patients,and are independent predictors of poor prognosis.The combination of the indicators has a good predictive value for the prognosis of elderly DFU patients.

Objective To investigate the microbiota composition and diversity between autogenous and anautogenous Culex pipiens pallens, so as to provide insights into unraveling the pathogenesis of autogeny in Cx. pipiens pallens. Methods Autogenous and anautogenous adult Cx. pipiens pallens samples were collected at 25 ℃, and the hypervariable regions of the microbial 16S ribosomal RNA (16S rRNA) gene was sequenced on the Illumina NovaSeq 6000 sequencing platform. The microbiota abundance and diversity were evaluated using the alpha diversity index, and the difference in the microbiota structure was examined using the beta diversity index. The microbiota with significant differences in the abundance between autogenous and anautogenous adult Cx. pipiens pallens samples was identified using the linear discriminant analysis effect size (LEfSe). Results The microbiota in autogenous and anautogenous Cx. pipiens pallens samples belonged to 18 phyla, 28 classes, 70 orders, 113 families, and 170 genera, and the dominant phyla included Proteobacteria, Bacteroidetes, and so on. At the genus level, Wolbachia was a common dominant genus, and the relative abundance was (77.6 ± 11.3)% in autogenous Cx. pipiens pallens samples and (47.5 ± 8.5)% in anautogenous mosquito samples, while Faecalibaculum (0.4% ± 0.1%), Dubosiella (0.5% ± 0.0%) and Massilia (0.5% ± 0.1%) were specific species in autogenous Cx. pipiens pallens samples. Alpha diversity analysis showed that higher Chao1 index and ACE index in autogenous Cx. pipiens pallens samples than in anautogenous samples (both P values > 0.05), and lower Shannon index (P > 0.05) and Simpson index (P < 0.05) in autogenous Cx. pipiens pallens samples than in anautogenous samples. LEfSe analysis showed a total of 48 significantly different taxa between autogenous and anautogenous Cx. pipiens pallens samples (all P values < 0.05). Conclusion There is a significant difference in the microbiota diversity between autogenous and anautogenous Cx. pipiens pallens.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To explore the role of serum cholinesterase (CHE) levels in the prognosis of patients with acute decompensated heart failure (ADHF).Methods:Total of 244 consecutive patients with ADHF who were admitted to the emergency department and were successfully discharged were prospectively enrolled from January 2018 to June 2020. Patients were divided into groups according to the first and third quartile of CHE level and the clinical data, laboratory tests and other nutritional indices were recorded after discharge, and then were followed up. The primary end points were the composites of cardiovascular death and hospitalization for worsening HF (composite end points). The secondary end points were all-cause mortality and cardiovascular death. Cox proportional risk analysis, time-dependent Cox regression model or stratified cox regression were used to identify the risk of primary and secondary endpoints. Clinical, biomarker and the compound models of clinical and biomarker were constructed. Kaplan-Meier method was used to plot the survival curves of different groups and compare their differences. Receiver Operating characteristics (ROC) curves were used to compare the area under the curve for CHE levels and other nutritional or prognostic indicators to identify composite end-point events.Results:During a follow-up period of 350(100,683) days, 158 patients reached the composite end points. In the multivariable Cox analysis, cholinesterase level was significantly associated with the composite end points after adjustment for major confounders. Cox proportional risk analysis or time-dependent Cox regression model showed that CHE level was significantly associated with the composite end points, all-cause mortality and cardiovascular mortality in both clinical, biomarker and composite models (all P< 0.05). A Kaplan–Meier analysis revealed that patients with low cholinesterase levels had significantly greater risk of reaching the composite end points than those with middle or high cholinesterase levels (78.1% vs 66.7% vs. 46.7%, P<0.001); Cholinesterase level showed the largest area under the receiver operating characteristic curve (AUROC) of 0.736 (95% CI, 0.664-0.888) for prediction of the composite end points among other nutritional indices. The AUROC of the Global Meta-Analysis Group Chronic Heart Failure (MAGGIC) Risk Score for prediction of the composite end points was increased from 0.704 to 0.762 ( P=0.038), when cholinesterase level was added. Conclusions:Cholinesterase may serve as a simple and effective prognostic marker for predicting adverse outcomes in ADHF patients.

Purpose To investigate the clinical and patho-logical characteristics,molecular characteristics,treatment and prognosis of systemic ALK-negative anaplastic large cell lympho-ma(ALCL).Methods Retrospective analysis was conducted on the clinical pathology,immunophenotype,molecular charac-teristics,treatment and prognosis of 18 cases of systemic ALK-ALCL.HE,immunohistochemistry,FISH,and NGS tests were performed,and relevant literatures were reviewed.Results Systemic ALK-ALCL tended to occur in elderly men,often in the advanced stage,mainly in lymph node lesions.The extran-odal primary sites included the primary pancreas and primary thoracic vertebrae.Morphological examination showed 17 cases belong to common type,1 case belong to"Hodgkin like"type.CD30 was diffuse and strongly positive in tumor cells(＞75％),CD2(16/17),CD3(13/18),CD5(4/18),CD7(8/18),CD4(14/18),TIA-1(16/18),CD8(2/16),GATA-3(10/12),EMA(3/5),MUM1(12/12),CD43(6/6)and CD56(2/8)were positive to varying degrees.The Ki67 proliferation index of 30％to 90％,PD-L1(22C3)(TPS=0-100％),ALK,CD15,CD79α and CD20 were all negative.FISH detection:5 cases of TP63 deficiency and 2 cases of DUSP22 deficiency;NGS detection:16 cases of gene mutations occurred,with a fre-quency of 0-11 gene mutations and an average of 4.2 gene mu-tations;ALK-ALCL with TP63 rearrangement was more likely to occur in women,mostly in lymph nodes,late clinical staging,susceptibility to p53 gene abnormalities,low PD-L1 expression rate and high mortality rate.Conclusion Systemic ALK-ALCL with TP63 rearrangement is associated with many adverse factors,the clinical process is often invasive with poor progno-sis.