Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10％L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9％NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P＜0.05,P＜0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P＜0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Medicine, Chinese Traditional ; Atherosclerosis/drug therapy* ; Lipoproteins ; Plaque, Atherosclerotic ; Biomarkers

ObjectiveTo explore the possible mechanism of pediatric tuina therapy in treating anorexia nervosa. MethodsTotally 120 children with anorexia nervosa were randomly divided into a tuina group and a medication group， with 60 cases in each group. Sixty healthy children undergoing physical examinations were recruited as the healthy control group. Children in the tuina group received traditional pediatric tuina therapy， while those in the medication group received orally chewed Jianwei Xiaoshi tablets. Each treatment course lasted for 7 days， with a 1-day interval between courses， and a total of 4 courses were administered. Before and after treatment， seven indicators including gastric motility frequency， gastric area， gastric area 30 minutes after drinking， anterior-posterior diameter and area during gastric fundus dilation， anterior-posterior diameter and area during gastric fundus contraction were measured using a color Doppler ultrasound diagnostic instrument in children from the healthy control group， tuina group， and medication group. Additionally， gastric emptying rate at 30 minutes， changes in anterior-posterior diameter and area during gastric fundus contraction， and changes in gastric area were compared. ResultsThis study ultimately included 60 healthy children in the control group， 59 children in the tuina group， and 51 children in the medication group. Compared with the control group at baseline， the gastric area and the anterior-posterior diameter and area during gastric fundus contraction increased， while the gastric emptying rate， gastric motility frequency， and changes in anterior-posterior diameter during gastric fundus contraction decreased in both the tuina group and medication group， with only a decrease in gastric area during gastric fundus contraction observed in the tuina group （P＜0.05）. Compared with baseline， after treatment， the gastric emptying rate， gastric motility frequency， and changes in anterior-posterior diameter and area during gastric fundus contraction increased in the tuina group， while the gastric area and area during gastric fundus contraction decreased 30 minutes after treatment； in the medication group， gastric motility frequency and changes in anterior-posterior diameter during gastric fundus contraction increased， while the area during gastric fundus contraction decreased （P＜0.05 or P＜0.01）. Compared with the medication group after treatment， the gastric area decreased 30 minutes after treatment， while the gastric emptying rate and gastric motility frequency increased （P＜0.05）. ConclusionThe possible mechanism of pediatric tuina therapy in treating anorexia nervosa is to promote gastric motility and gastric emptying， thereby improving gastrointestinal dysfunction in children.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective To investigate the molecular mechanism of Brusatol(BRU)regulating apoptosis of Hela cells through TLR9-MyD88 signaling pathway.Methods Hela cells preserved in our laboratory were treated with Brucea javanica at different concentrations(0,5.0,10.0,20.0,40.0,80.0 nmol·L-1).Hela cells were divided into Control group(normal cultured Hela cells),BRU-L group(treated with 10.0 nmol·L-1 Brucea javanica)and BRU group-H(treated with 20.0 nmol·L-1 Brucea javanica)Cells were treated with nmol·L-1 of Brucea javanica),BRU+pcDNA-NC group(transfected with pcDNA-NC+20.0 nmol·L-1 of Brucea javanica),BRU-H+pcDNA-TLR9 group(transfected with pcDNA-TLR9+20.0 nmol·L-1 of Brucea javanica).Cell proliferation was detected by CCK-8 and EdU methods.Apoptosis was detected by TUNNEL staining and flow cytometry.The protein expression levels of TLR9,MyD88,Bax,Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were detected by Western blot.Cell apoptosis and mitochondrial membrane potential detection kit(JC-1)were detected by flow cytometry,and the contents of adenosine triphosphate(ATP)and reactive oxygen species(ROS)were detected by ELISA.Results Compared with 0 nmol·L-1 group,the survival rate and IC50 value of 10 nmol·L-1 group were significantly decreased(P<0.05).After stimulation of BRU with different concentrations,the proliferation ability of cells was significantly decreased in a dose-dependent manner(P<0.05).Compared with control group,the 5-ethynyl-2'-deoxyuracil(EDU)positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein of cells in BRU-L,BRU-H and pcDNA-NC groups were significantly decreased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly increased(P<0.05).In control group,BRU-L,BRU-H group/BRU-H+pcDNA-NC,there was a continuous decreasing trend(P<0.05).Compared with the BRU-H+pcDNA-NC group,the EDU positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein in the BRU-H+pcDNA-TLR9 group were significantly increased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly decreased(P<0.05).Compared with Control group,JC-1 level and ATP content in BRU-L,BRU-H and BRU-H+pcDNA-NC groups were significantly decreased,while ROC content and mitotracker positive cell level were significantly increased(P<0.05).Compared with BRU-L group,JC-1 level and ATP content in BRU-H group and BRU-H+pcDNA-NC group were further decreased,while ROC content and mitotracker positive cell level were further increased(P<0.05).Compared with the BRU-H+pcDNA-NC group,the levels of JC-1 and ATP in the BRU-H+pcDNA-TLR9 group were increased,while the levels of ROC,mitotracker staining positive cells were decreased(P<0.05).Conclusion Brucea javanica can produce Hela cell proliferation by regulating TLR9-MyD88 signaling pathway.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

The presence of 4-aminophenol(4-AP)in wastewater from the pharmaceutical industry is a common occurrence due to its role as a byproduct or intermediate during the hydrolysis process of paracetamol metabolism,resulting in significant water pollution.Therefore,it is crucial to employ a straightforward and reliable analytical approach for detecting 4-AP in the environment.In this study,a specific type of metal-organic framework(MOF)material called[Cd4(ABTC)2(H2O)12]n(SXNU-4-Cd,H4ABTC=3,3′,5,5′-azobenzene tetracarboxylic acid)was successfully synthesized,which exhibited a unique two-dimensional layered structure consisting of three intertwined spiral chains forming a distinctive″twist braid″.These layers underwent π-π stacking,creating three-dimensional channels with azo bonds decorating the channel walls.This p-π interaction significantly enhanced the adsorption capacity of SXNU-4-Cd towards 4-AP,thereby improving its recognition sensitivity.The fabricated SXNU-4-Cd/GCE sensor showed high sensitivity towards 4-AP in the linear concentration range of 0.1-130 μmol/L,with a detection limit of 8.6 nmol/L,and also exhibited good anti-interference capability,reproducibility and stability.The SXNU-4-Cd/GCE sensor was successfully used for detecting 4-AP in lake water sample,with spiked recoveries of 95.9%-102.8%.This study introduced a novel technique that utilized pure Cd-MOFs to develop electrochemical sensor capable of effectively detecting 4-AP in water samples.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.