ObjectiveTo investigate the effects of Hei Xiaoyaosan on neuroinflammation in APP/PS1 mice and decipher the mechanism based on the C-X3-C chemokine ligand 1 （CX3CL1）-CX3CL1 receptor 1 （CX3CR1） signaling axis. MethodsSixty 16-week-old male APP/PS1 mice were selected and acclimatized for one week， and they were then randomly allocated into a model group， a CX3CL1 group （bilateral hippocampal injection of CX3CL1 at 0.5 g·L^-1）， and high-， medium-， and low-dose （22.10， 11.05， and 5.53 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 12 mice in each group. Twelve age-matched male C57BL/6J mice served as the blank group （bilateral hippocampal injection of an equal volume of PBS）. The high-， medium-， and low-dose Hei Xiaoyaosan groups received corresponding drugs via gavage， while the blank group received an equal volume of normal saline， with an intervention period of 90 days. Morris water maze was used to assess learning and memory abilities. Nissl staining was performed to observe the pathological changes in neurons of the hippocampal CA1 region. Immunohistochemistry was adopted to detect amyloid-β_1-42 （Aβ_1-42） deposition in the hippocampal CA1 region. The immunofluorescence assay was employed to detect the expression of M1 and M2 microglial markers， including cluster of differentiation 86 （CD86）/ionized calcium-binding adapter molecule 1 （Iba-1） and arginase-1 （Arg1）/Iba1. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-8 （IL-8） and interleukin-13 （IL-13） in the hippocampal tissue. Western blot was employed to determine the protein levels of CX3CL1， CX3CR1， CREB-binding protein （CBP）， cyclic AMP response element-binding protein （CREB）， phosphorylated （p）-CREB， and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group exhibited prolonged escape latency on day 5 and a reduced swimming distance in the target quadrant （P<0.01）， disarrangement of hippocampal neurons， with a reduced number of cells and uneven Nissl body staining， increased CD86/Iba1 expression， decreased Arg1/Iba1 expression （P<0.01）， enhanced Aβ expression （P<0.01）， an elevated IL-8 level and a declined IL-13 level （P<0.01）， and downregulated protein levels of CX3CL1， CX3CR1， CBP， p-CREB， and BDNF （P<0.01）. Compared with the model group， all treatment groups showed shortened escape latency on day 5 and an increased swimming distance in the target quadrant （P<0.05， P<0.01）， regular arrangement of neurons with an increased number and increased Nissl bodies， reduced CD86/Iba1 expression， increased Arg1/Iba1 and decreased Aβ expression （P<0.01）， and a declined IL-8 level and an elevated IL-13 level （P<0.05， P<0.01）. In the CX3CL1 group and the high- and medium-dose Hei Xiaoyaosan groups， the relative expression levels of CX3CL1， CX3CR1， CBP， and p-CREB were upregulated （P<0.01）. In the low-dose Hei Xiaoyaosan group， the relative expression levels of CX3CL1， CX3CR1， CBP， p-CREB/CREB， and BDNF were upregulated （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can improve learning and cognitive abilities in APP/PS1 mice. Specifically， it may regulate the CX3CL1/CX3CR1 signaling axis to activate the CREB/BDNF signaling pathway for the subsequent release of BDNF， modulation of microglial polarization， reduction of inflammatory cytokine levels， and attenuation of Aβ deposition.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Frailty is a common clinical syndrome in the elderly, with unexplained weight loss, low grip strength, fatigue, slow walking speed and reduced physical activity. The decline of cognitive function interacts with the occurrence and development of frailty symptoms. As the highest level of cognitive function, executive function is of great significance in regulating body function. This article reviews the definition, assessment tools, related research and mechanism of senile frailty and executive function, and explores the relationship between executive function and the occurrence and development of frailty. This article also points out the existing problems in the relevant research and puts forward targeted suggestions to promote the healthy aging of the elderly in China.

Objective: Saposhnikoviae Radix (Fangfeng in Chinese), the roots of Saposhnikovia divaricata, lacks commodity specification and grade standardization in the current market. This study investigated the existing specifications and grades of Saposhnikoviae Radix to provide a standardized scientific reference for its market use. Methods: Based on a textual research of Chinese herbal medicine from the Han Dynasty to the present, medicinal materials of different specifications and grades obtained from Saposhnikoviae Radix in the main producing areas of China were collected and the markets for these materials were investigated. Field investigations were performed in the major producing areas such as Northeast China, Hebei Province, and Inner Mongolia. Four major Chinese herbal medicine markets in China were investigated. Sensory indices were used to categorize the two specifications (wild and cultivated) according to the shape, color, texture, and cross-section. High-performance liquid chromatography was performed to determine the active components. Vernier calipers and measuring tape were used to measure the diameter and length, respectively, of 41 samples. Using Excel and the R Language software, cluster analysis and descriptive statistical analysis were performed to assist in the application of new specifications and grades based on physical characteristics, pharmacological activity, and chemical composition. Results: The two specifications (wild and cultivated) of Saposhnikoviae Radix were divided into three grades each based on the length and diameter. Prim-O-glucosylcimifugin, 5-O-methylvisamminoside, and the length of Saposhnikoviae Radix can be used as a basis for classifying the commodity specifications and grades. The specifications and grade standards of Saposhnikoviae Radix were established based on the following eight aspects: shape, surface characteristics, texture, cross section, taste, prim-O-glucosylcimifugin content, 5-O-methylvisamminoside content and length. Conclusion: The formulation of this standard stipulates the commodity specification level of Saposhnikoviae Radix. It is also suitable for the evaluation of commodity specifications in the process of production, circulation and use of Saposhnikoviae Radix.

Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.

Objective:To investigate the body composition and sarcopenia in patients with stable chronic obstructive pulmonary disease (COPD) and to analyze the influencing factors.Methods:A total of 220 patients with stable COPD were enrolled in the study from China-Japan Friendship Hospital during July 2018 to December 2019; 220 age and sex-matched healthy subjects (control group 1) and 220 healthy young adults aged 20-40 years (control group 2) were enrolled from the community. The body composition was measured by bioelectrical impedance method. The demographic characteristics, disease conditions, living background and other related factors were collected by questionnaire. T test or one-way ANOVA were used for comparison between groups, and non parametric test was used for non normal distribution data.Results:Compared with the control group 1 and control group 2, the body fat rate ( Z=-10.037, t=-8.411), the fat free mass index ( Z=-8.165, t=-7.856), and appendicular skeletal muscle index (ASMI) ( t=-7.158, t=-11.989) were significantly lower in stable COPD patients ( P<0.05). Among 220 patients with stable COPD, 51 (23.2%) were diagnosed as sarcopenia; the prevalence of sarcopenia was 18.3% (24/131) in men and 30.3% (27/89) in women (χ2=4.297, P=0.038). The decreased ASMI and grip strength in COPD patients with sarcopenia were significantly associated with age≥75 (χ2= 15.746, F= 14.048), female sex ( Z=5.805, t=2.672), low income ( Z=-4.291, t=-4.789), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade Ⅳ (χ2=22.644, F=3.905), Modified British Medical Research Council (mMRC) Dyspnea Scale grade 4 (χ2=12.475, F=4.369), not receiving systematic health education ( Z=-4.239, Z=-2.474), no exercise (χ2=14.786, F=3.402), insufficient nutrition intake (χ2=40.531, F=10.529). The range of 6-min walking distance was (110-268) m, that was even shorter for patients with mMRC dyspnea scale grade 4 ( F=3.468, P<0.05). Conclusion:The impairment of body composition is common in COPD patients, which will further affect the body function. It is suggested that the routine evaluation of COPD should include the measurement of body composition.

Objective: To investigate the status of knowledge about acquired immune deficiency syndrome(AIDS) among college freshmen in Jiangsu Province, and to analyze the influences of AIDS-related knowledge on their sexual attitudes and behaviors. Methods: A total of 8 633 freshmen from 20 colleges and universities in Jiangsu Province were enrolled by multi-stage stratified sampling. The questionnaire for young students about the eight items of AIDS basic knowledge were used to investigate the AIDS-related knowledge, sexual attitudes and behaviors. Multivariate Logistic regression model was used to analyze the influencing factors of the AIDS-related knowledge and to adjust the influences of AIDS-related knowledge on sexual attitudes and behaviors. Results: The overall qualified rate of AIDS-related knowledge among college freshmen in Jiangsu Province was 87.6% and the qualified rate of 8 items were between 59.8% and 98.3%. The types of schools, nationality, mother s education level and whether only child or not were identified as independent factors for qualified rate of AIDS-related knowledge(P<0.05). The awareness of AIDS-related knowledge had significant impacts on the sexual attitudes and behaviors of college freshmen. Students with insufficient knowledge were more likely to approve premarital sexual behaviors(OR=1.31, 95%CI=1.11-1.63), willing to use condoms consistently(OR=1.67, 95%CI=1.43-1.92) and to accept the HIV tests(OR=4.54, 95%CI=3.13-6.52). Students with unqualified knowledge were more likely to have sexual behavior(OR=1.89, 95%CI=1.42-2.49), while those with sexual experiences and insufficient AIDS knowledge were more likely to use condoms consistently(OR=2.13, 95%CI=1.22-3.78). Conclusion The education on AIDS-related knowledge for teenagers was helpful to construct correct sexual concepts and develop healthy sexual behaviors. However, the AIDS-related knowledge of college freshmen in Jiangsu Province is not sufficient and needed to improve.