Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

OBJECTIVES: To investigate the epidemiological characteristics of human metapneumovirus (hMPV) and the risk factors for severe pneumonia in hospitalized children. METHODS: The epidemiological characteristics of hMPV in hospitalized children at Hebei Children's Hospital from January 2019 to December 2023 were retrospectively analyzed. The clinical data of hospitalized children with hMPV infection from April to December 2023 were included, and independent risk factors for severe pneumonia were identified through logistic regression. RESULTS: A total of 44 092 children were tested, with an hMPV positive rate of 7.30% (3 220/44 092). Children aged 3-6 years constituted the largest proportion (40.93%, 1 318/3 220) among hMPV-positive cases. The detection rate varied significantly by year (P<0.001), peaking in 2022 (12.35%, 978/7 919). The peak season of the epidemic was winter and spring from 2019 to 2021, but shifted to spring and summer from 2022 to 2023. The proportion of co-infection was 38.70% (1 246/3 220), primarily with rhinovirus (600/1 246, 48.15%), Mycoplasma pneumoniae (217/1 246, 17.42%), and respiratory syncytial virus (182/1 246, 14.61%). The main manifestations of hMPV pneumonia were cough, expectoration, and fever. Children with severe pneumonia were significantly younger (P<0.05). Wheezing, underlying diseases, co-infection, and younger age were identified as independent risk factors for severe pneumonia (P<0.05). CONCLUSIONS There are significant annual and seasonal differences in the epidemiological characteristics of hMPV in hospitalized children. Young age, underlying diseases, wheezing, and co-infection are independent risk factors for severe pneumonia.
Humans ; Risk Factors ; Metapneumovirus ; Child, Preschool ; Child ; Male ; Female ; Paramyxoviridae Infections/complications* ; Pneumonia/epidemiology* ; Retrospective Studies ; Child, Hospitalized ; Infant ; Logistic Models ; Seasons ; Hospitalization

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

ObjectiveTo investigate the effect of 8-week aerobic exercise on the improvement of core behaviors of male and female autistic mice induced by valproic acid (VPA). MethodsExperimental mice were randomly divided into the control group (CTL), VPA-induced autism group (VPA) and VPA+aerobic exercise group (VEX), with 10 mice in each group. The pregnant mice were injected with VPA intraperitoneally at E12.5, and their offspring were used as autistic mice. Pups were weaned 28 d after birth and began an 8-week aerobic exercise intervention. The day after exercise, mice were tested in behavioral experiments to detect exploratory behavior, social skills, repetitive stereotypic behavior, cognitive ability and mood. The mice were tested for social skills, repetitive stereotyped behaviors, cognitive and learning memory abilities, exploratory behaviors, and emotions by behavioral assays on the following day after the exercise. ResultsBoth male and female mice in the CTL group showed a significant decrease in the total distance and percentage of time spent in the interaction zone in the 4th socialization compared to the 1st socialization (P<0.01); the total distance and percentage of time spent in the interaction zone in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01); in VPA group, both male and female mice showed no significant change in the total distance and percentage of time spent in the interaction zone in the 4th and 5th socialization; in the VEX group, the total distance and percentage of time spent in the interaction zone by male mice in the 4th socialization was significantly decreased compared to the 1st socialization (P<0.01, P<0.05); and in the VEX group the total distance and percentage of time spent in the social interaction zone by both male and female mice in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01, P<0.05). The results of the first phase of three-box socialization experiment showed that male and female mice in the CTL group spent more time socializing with their social partners than in contact with the empty cages (P<0.01); there was no difference in the time spent by male and female mice in the VPA group in socializing with their social partners and the empty cages; and male and female mice in the VEX group spent a longer time socializing with their social partners(P<0.01). The results of the second phase of three-box test showed that male and female mice in the CTL group showed a significant tendency to socialize with new social partners (P<0.01), whereas no significant changes were observed in the mice of VPA group; aerobic exercise significantly ameliorated this deficit in male and female mice with autism. Compared with the CTL group, VPA-induced significant decreases were observed in the total distance freely moved in the central area of the open field, the time and percentage of time spent in the open arm of cross maze, and the distance and time spent in the white box in both male and female autistic mice (P<0.01); a significant increase in the number of bead burials and time spent in self-grooming (P<0.01); a significant decrease in the cognitive index (P<0.01); a significantly longer latency to find the platform, and significantly decreased the percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01). Compared with the VPA group, after 8 weeks of aerobic intervention, male and female mice in the VEX group showed a significant increase in total distance, open-arm dwell time, and percentage of free movement in the central area of the empty field (P<0. 05), and a trend toward a decrease in the dwell time of females in the white box was not significant, the number of beads burying and the time of self-combing were significantly lower(P<0.01, P<0.05); and a significant increase in cognitive index (P<0.05), a significantly shorter time to find the platform, and significantly increased percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01), showing excellent learning memory. ConclusionAutistic mice severely suffer from social and cognitive impairments, repetitive stereotyped behaviors, decreased activity level, and the exhibition of anxiety. 8 weeks of aerobic exercise can improve the social and cognitive abilities, alleviate the stereotyped repetitive behaviors, increase the activity level, and positively regulate the anxiety in autistic mice. It is hypothesized that aerobic exercise has an important role in motor rehabilitation of autism, in order to provide a theoretical basis for clinical research.

Circulating tumor DNA (ctDNA) comes from tumor, reflecting the genetic information of the tumor well, and will change with the progress of tumor. In recent years, the unique capabilities of ctDNA have attracted much attention and been widely studied. In this paper, based on the summary of the source, properties and sample processing of ctDNA, its detection technology and application in cancer diagnosis and treatment are reviewed. The roles and importance of ctDNA reference material in second-generation sequencing are described. The urgency of establishing uniform standards and specifications of ctDNA in various processes, such as samples collection, storage, quantitative testing and data analysis, has been pointed out.

Child ; Humans ; Mpox (monkeypox)/prevention & control* ; Disease Outbreaks

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Objective To investigate the clinical effect of unilateral percutaneous vertebroplasty(PVP)combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.Methods A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study,all of which were vertebral body compression fractures caused by trauma.According to different treatment methods,they were di-vided into experimental group and control group.Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group,there were 5 males and 27 females,aged from 63 to 91 years old with an average of(77.59±8.75)years old.Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty,including 7 males and 38 females,aged from 60 to 88 years old with an average of(74.89±7.37)years old.Operation time,intraoperative C-arm X-ray times,anesthetic dosage,bone cement injection amount,bone cement diffusion good and good rate,complications,vertebral height,kyphotic angle(Cobb angle),visual analogue scale(VAS),Oswestry disability index(ODI)and other indicators were recorded before and after surgery,and statistically analyzed.Results All patients were followed up for 6 to 23 months,with preoperative imaging studies,confirmed for thoracolumbar osteoporosis com-pression fractures,two groups of patients with postoperative complications,no special two groups of patients'age,gender,body mass index(BMI),time were injured,the injured vertebral distribution had no statistical difference(P＞0.05),comparable data.Two groups of patients with bone cement injection,bone cement dispersion rate,preoperative and postoperative vertebral body height,protruding after spine angle(Cobb angle),VAS,ODI had no statistical difference(P＞0.05).The operative time,intra-operative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P＜0.05).Compared with the traditional bilateral puncture group,the modified unilateral puncture group combined with 3D printing technology had shorter operation time,fewer intraoperative fluoroscopy times and less anesthetic dosage.The height of anterior vertebral edge,kyphosis angle(Cobb angle),VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P＜0.05).Conclusion In the treatment of thoracolumbar osteoporotic compression fractures,3D printing technology is used to improve unilateral puncture PVP,which is convenient and simple,less trauma,short operation time,fewer fluoroscopy times,satisfactory distribution of bone cement,vertebral height recovery and kyphotic Angle correction,and good functional improvement.

Objective To investigate whether Heshouwuyin can delay the aging of Leydig cells in rat testis through DNA methyltransferase 1(DNMT1).Methods Totally 40 male Wistar rats were randomly divided into 4 groups,with 10 rats in each group.Immunohistochemistry was used to detect the expression levels of DNMT1 in testis tissue of rats.Testosterone content in serum of rats in each group was detected by ELISA test.A rat Leydig cell aging model was established by free radical oxidative damage.DNMT1 was knocked down by lentivirus in Leydig cells,and the cell senescence status and the testosterone content and testosterone synthesis key enzyme 3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 family member 11A1(CYP11A1)content secreted by cells were detected by β-galactosidase(β-GAL)staining,immunofluorescenct staining and ELISA.Results Compared with the young control group(YCG),the expression of P16 protein and the positive rate of β-GAL in the testis tissue of rats in the natural aging group(NAG)increased significantly,and the expression of DNMT1 and serum testosterone levels decreased(P＜0.05).However,after Heshouwuyin intervention,the expression of P16 protein and the positive rate of β-GAL in the testis of aging rats were reduced,and DNMT1 expression and the serum testosterone levels increased(P＜0.05).The same trend was observed in Leydig cells.Knockdown of DNMT1 in Leydig cells,β-GAL positivity and P16 protein expression increased significantly,and testosterone secretion and testosterone synthesis key enzymes 3β-HSD,CYP11A1 content from Leydig cells decreased significantly,compared with the normal control group(NCG)(P＜0.05).When Heshouwuyin was added,the above phenomenon was improved.Conclusion Heshouwuyin can delay the aging of rat Leydig cells through DNMT1.

Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.