ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9％NaCl),model group(intraperitoneal injection of 0.9％NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P＜0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P＜0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P＜0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

During the development of whole-cell microbial sensors,factors such as cellular metabolic activity and signal output modes play pivotal roles in the stability and repeatability of the sensors,presenting numerous challenges for the standardization of sensor applications. This research focused on the arsenic ion sensor based on the RepL amplifier,adjusting the reporter genes,culture media,growth stages,and induction times of arsenic ions,aiming to investigate how these factors affect the sensor's detection performance. The results indicated that the cell's culturing environment,growth status (e.g.,different growth phases),type of reporter,and induction time all had significant impacts on the performance of the arsenic ion sensor. First,the stability of the sensors varied greatly in different media,all the three sensors displayed greater stability in LB culture medium. Meanwhile,the cells in different growth stages also exhibited different performance advantages. Cells at the stationary growth phase exhibited better detection sensitivity and linearity,while cells in the logarithmic growth phase had lower limit of detection (LOD) . Moreover,there was an optimal induction time for the response of the sensor,overly long or short induction time could interfere with its response. The optimal induction time for the arsenic sensor in this work was about 2-3 h. By comparing three types of fluorescent protein reporters,it was found that although their detection limits were fairly similar,all within the range of 5-10μg/L,but their response times varied,ranging from 40 min to 2 h. The fluorescent proteins with higher brightness exhibited faster sensor response. These research outcomes provided a solid foundation for the practical application of microbes in detection. In practice,we could choose cells in specific states based on particular purpose,maximizing the performance of the cell sensors and further broadening the application scope of such sensors.

Objective To investigate the efficacy of Bushen Tiaojing Decoction,a prescription derived from Daying Decoction which recorded in Jing Yue Quan Shu(The Complete Works of ZHANG Jing-Yue)and with herbs added,combined with human recombinant interferon-α-2b for the treatment of endometriosis(EMs)and to observe its effects on humoral immunity,serum carbohydrate antigen 125(CA125)and anti-endometrial antibody(EMAb)levels of EMs patients.Methods A total of 86 cases of EMs patients with kidney deficiency and blood stasis syndrome were randomly divided into observation group and control group,with 43 cases in each group.The control group was treated with human recombinant interferon-α-2b alone,and the observation group was treated with Bushen Tiaojing Decoction combined with human recombinant interferon-α-2b.The course of treatment covered one month.The changes of humoral immune factors of immunoglobulin A(IgA),complement 3(C3)and complement 4(C4),endometrial ectopic mass diameter,and the levels of pathology-relevant factors of CA1 25 and EMAb in the two groups before and after treatment were observed.Moreover,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate of the observation group was 97.67％(42/43),and that of the control group was 81.40％(35/43).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the serum IgA level of the two groups was significantly higher than that before treatment(P＜0.05),and the serum C3 and C4 levels were significantly lower than those before treatment(P＜0.05).The increase of serum IgA level and the decrease of serum C3 and C4 levels in the observation group were significantly superior to those in the control group(P＜0.01).(3)After treatment,the serum CA125 and EMAb levels and the diameter of endometrial ectopic mass in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum CA125 and EMAb levels and the diameter of endometriosis mass in the observation group was significantly superior to that in the control group(P＜0.01).(4)The total incidence of adverse reactions in the observation group was 6.98％(3/43)and that in the control group was 11.63％(5/43),and the difference between the two groups was not significant(P＞0.05).Conclusion Bushen Tiaojing Decoction combined with human recombinant interferon-α-2b has a significant clinical effect for the treatment of EMs patients with kidney deficiency and blood stasis syndrome.The combined therapy is effective on improving the levels of humoral immune factors,serum CA125 and EMAb,and reducing endometrial ectopic mass,with high safety.

Purpose To analyze the expression of TRPS1 protein in breast cancer and lung cancer and its difference,and to explore the diagnostic value of TRPS1 protein in differential diagnosis between lung metastasis from breast cancer and prima-ry lung cancer.Methods A total of 369 cases of breast canc-er,57 cases of primary lung cancer(23 cases of surgical resec-tion samples,34 cases of biopsy samples),and 35 cases of lung metastases from breast cancer(3 cases of surgical resection sam-ples,32 cases of biopsy samples)were collected.Immunohisto-chemical EnVision method was used to detect the expression of TRPS1 protein in all cases and to analyze its expression differ-ences.Results TRPS1 protein was expressed in 369 cases of breast cancer,of which 93.2％cases showed diffusely strongly positive expression(≥95％ strongly positive expression in tumor cell nucleus),6.8％ cases showed heterogeneous expres-sion of tumor cells,and the tumor types were mainly breast cancer with sweat gland differentiation and metaplastic cancer.Among 57 cases of primary lung cancer,28.1％of cases were negative for TRPS1,70.2％ of cases showed heterogeneous ex-pression,manifested as varying degrees of nuclear staining or only focal nuclear staining,and heterogeneous expression was dominant in different histological types including adenocarcino-ma,squamous cell carcinoma,and neuroendocrine carcinoma.In addition,TRPS1 was observed to be diffusely strongly positive in one(1.7％)lung adenocarcinoma biopsy sample.Among 35 cases of lung metastases from breast cancer,including surgical resection samples and biopsy samples,100％cases showed dif-fusely strongly positive expression of TRPS1.The expression of TRPS1 in lung metastasis of breast cancer and primary lung cancer was significantly different(P＜0.001).Conclusion TRPS1 protein is a highly sensitive and specific biomarker for breast cancer,but it can still be expressed in other tumors such as lung cancer,and it is also observed that TRPS1 is expressed to varying degrees in various histological types of lung cancer,which has certain diagnostic value in differentiating lung metas-tases from primary lung cancer in breast cancer,but it cannot be used as a single diagnostic marker,especially in small biopsy tissues of lung nodules.Therefore it is necessary to use multiple biomarkers to comprehensively determine the source of metasta-ses to improve the diagnostic accuracy,so as to guide follow-up clinical treatment.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the amplitude-integrated electroencephalography(aEEG)monitoring results of hospitalized neonates in plateau areas.Methods A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology,Kunming Children's Hospital,and received aEEG monitoring from January 2020 to December 2022.According to the aEEG monitoring results,they were divided into a normal aEEG group and an abnormal aEEG group.The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases,as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities.Results Among the 5 945 neonates,the aEEG abnormality rate was 19.28%(1 146/5 945),with an abnormality rate of 29.58%(906/3 063)in critically ill neonates and 8.33%(240/2 882)in non-critically ill neonates(P<0.05).The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77%(79/130),followed by those with central nervous system disorders[42.22%(76/180)]and preterm infants[35.53%(108/304)].Compared with the normal aEEG group,the abnormal aEEG group had significantly lower age and gestational age,as well as a significantly lower birth weight of preterm infants(P<0.05).Among the 1 146 neonates with aEEG abnormalities,the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates(52.09%),background activity abnormalities in 294 neonates(25.65%),and epileptiform activity in 255 neonates(22.25%),and there were 902 neonates(78.71%)with abnormal clinical manifestations.The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51%and 92.50%,respectively.Conclusions In plateau areas,there is a relatively high rate of aEEG abnormalities among hospitalized neonates,particularly in critically ill neonates and those with smaller gestational ages and younger ages,suggesting a high risk of brain injury.Therefore,routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities,the decision-making in treatment,and the formulation of brain protection strategies.