This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

Moringa oleifera, widely utilized in Ayurvedic medicine, is recognized for its leaves, seeds, and velamen possessing traditional effects such as vātahara(wind alleviation), sirovirecaka(brain clearing), and hridya(mental nourishment). This study aims to identify the medicinal part of ■ in the Sārasvata ghee formulation as described in the Bower Manuscript, while investigating the ameliorative effects of different medicinal parts of M. oleifera on learning and memory deficits in mice and elucidating the underlying molecular mechanisms. A total of 144 male ICR mice were randomly assigned to the following groups: control, model(scopolamine hydrobromide, Sco, 2 mg·kg~(-1)), donepezil(donepezil hydrochloride, Don, 3 mg·kg~(-1)), M. oleifera leaf low-, medium-, and high-dose groups(0.5, 1, 2 g·kg~(-1)), M. oleifera seeds low-, medium-, and high-dose groups(0.25, 0.5, 1 g·kg~(-1)), and M. oleifera velamen low-, medium-, and high-dose groups(0.31, 0.62, 1.24 g·kg~(-1)). Learning and memory abilities were assessed using the passive avoidance test and Morris water maze. Nissl and HE staining were employed to examine histopathological changes in the hippocampus. Transcriptomics and targeted metabolomics were used to screen differential genes and metabolites, with MetaboAnalyst 6.0 and O2PLS methods applied to identify key disease-related targets and pathways. RESULTS:: demonstrated that M. oleifera leaf(1 g·kg~(-1)) significantly ameliorated Sco-induced learning and memory deficits, outperforming M. oleifera seeds(0.25 g·kg~(-1)) and M. oleifera velamen(1.24 g·kg~(-1)). This was evidenced by improved behavioral performance, reversal of neuronal damage, and reduced acetylcholinesterase(AChE) activity. Multi-omics analysis revealed that M. oleifera leaf upregulated Tuba1c gene expression through the synaptic vesicle cycle, enhancing glutamate(Glu), dopamine(DA), and acetylcholine(ACh) release via Tuba1c-Glu associations for neuroprotection. M. oleifera seeds targeted the dopaminergic synapse pathway, promoting memory consolidation through Drd2-ACh associations. M. oleifera velamen was associated with the cocaine addiction pathway, modulating dopamine metabolism via Adora2a-DOPAC, with limited relevance to learning and memory. In conclusion, M. oleifera leaf exhibits superior efficacy and mechanistic advantages over M. oleifera seeds and velamen, suggesting that the ■ in the Sārasvata ghee formulation is likely M. oleifera leaf, providing scientific evidence for its identification in ancient texts.
Animals ; Moringa oleifera/chemistry* ; Male ; Mice ; Seeds/chemistry* ; Plant Leaves/chemistry* ; Mice, Inbred ICR ; Memory Disorders/psychology* ; Transcriptome/drug effects* ; Memory/drug effects* ; Learning/drug effects* ; Metabolomics ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Maze Learning/drug effects*

From the perspective of competitive endogenous RNA(ceRNA) constructed by metastasy-associated lung adenocarcinoma transcript 1(Malat1) and microRNA 16-5p(miR-16-5p), the improvement mechanism of Tonggu Xiaotong Capsules(TGXTC) on the imbalance and disorder of "cholesterol-iron" metabolism in chondrocytes of osteoarthritis(OA) was explored. In vivo experiments, 60 8-week-old C57BL/6 mice were acclimatized and fed for 1 week and then randomly divided into two groups: blank group(12 mice) and modeling group(48 mice). The animals in modeling group were anesthetized by 5% isoflurane inhalation, which was followed by the construction of OA model. They were then randomly divided into model group, TGXTC group, Malat1 overexpression group, and TGXTC+Malat1 overexpression(TGXTC+Malat1-OE) group, with 12 mice in each group. The structural changes of mouse cartilage tissues were observed by Masson staining after the intervention in each group. RT-PCR was employed to detect the mRNA levels of Malat1 and miR-16-5p in cartilage tissues. Western blot was used to analyze the protein expression of ATP-binding cassette transporter A1(ABCA1), sterol regulatory element-binding protein(SREBP), cytochrome P450 family 7 subfamily B member 1(CYP7B1), CCAAT/enhancer-binding protein homologous protein(CHOP), acyl-CoA synthetase long-chain family member 4(ACSL4), and glutathione peroxidase 4(GPX4) in cartilage tissues. In vitro experiments, mouse chondrocytes were induced by thapsigargin(TG), and the combination of Malat1 and miR-16-5p was detected by double luciferase assay. The fluorescence intensity of Malat1 in chondrocytes was determined by fluorescence in situ hybridization. The miR-16-5p inhibitory chondrocyte model was constructed. RT-PCR was used to analyze the levels of Malat1 and miR-16-5p in chondrocytes under the inhibition of miR-16-5p. Western blot was adopted to analyze the regulation of TG-induced chondrocyte proteins ABCA1, SREBP, CYP7B1, CHOP, ACSL4, and GPX4 by TGXTC under the inhibition of miR-16-5p. The results of in vivo experiments showed that,(1) compared with model group, TGXTC group exhibited a relatively complete cartilage layer structure. Compared with Malat1-OE group, TGXTC+Malat1-OE group showed alleviated cartilage surface damage.(2) Compared with model group, TGXTC group had a significantly decreased Malat1 mRNA level and an increased miR-16-5p mRNA level in mouse cartilage tissues(P<0.01).(3) Compared with the model group, the protein levels of ABCA1 and GPX4 in the cartilage tissue of mice in the TGXTC group increased, while the protein levels of SREBP, CYP7B1, CHOP and ACSL4 decreased(P<0.01). The results of in vitro experiments show that,(1) dual-luciferase was used to evaluate that miR-16-5p has a targeting effect on the Malat1 gene.(2)Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group had an increased mRNA level of miR-16-5p and an decreased mRNA level of Malat1(P<0.01).(3) Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group exhibited increased expression of ABCA1 and GPX4 proteins and decreased expression of SREBP, CYP7B1, CHOP, and ACSL4 proteins(P<0.01). The reasults showed that TGXTC can regulate the ceRNA of Malat1 and miR-16-5p to alleviate the "cholesterol-iron" metabolism disorder of osteoarthritis chondrocytes.
Animals ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Chondrocytes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Osteoarthritis/drug therapy* ; Iron/metabolism* ; Male ; Cholesterol/metabolism* ; Humans ; Capsules ; RNA, Competitive Endogenous

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

Licorice-gypsum (gancao-shigao, GC-SG) drug pair was used as the research object, using supramolecular chemistry to explore the scientific connotation of combining herbal medicine GC with insoluble mineral medicine SG in clinical application of traditional Chinese medicine. ① The Tyndall effect, microscopic morphology and particle size of the single and co-decocted of GC and SG were observed, the paste content and conductivity were determined, and the interaction between GC and SG was detected by isothermal titration calorimetry (ITC) and infrared absorption spectroscopy (IR). ② Calcium chloride (CaCl₂), a soluble calcium salt of equal gypsum quality, was used instead of SG with GC for co-decocting to explore the effect of calcium salt content on the water decocting, and the characteristics were combined with the Tyndall effect, microscopic morphology, paste content and conductivity. ITC and IR techniques were used to detect the interaction between the two, and the interaction between them was detected by ITC and IR. The zeta potential and ultraviolet-visible spectrophotometry (UV-vis) of GC-SG and GC-CaCl₂ co-decoction were compared, and the inorganic and organic components in the co-decoction were detected by inductively coupled plasma optical emission spectrometer (ICP-OES) and high performance liquid chromatography (HPLC). The results showed: ① Compared with the liquid phase of single decoction, GC-SG co-decoction had more obvious Tyndall effect, and showed uniform spherical nanoparticles under electron microscope. Physical characterization results such as paste content and conductivity showed that co-decoction promoted the dissolution of each other's components; ITC and IR results showed that there was strong interaction between GC and SG, which preliminatively indicated that GC and SG co-decoction promoted the formation of uniform and stable supramolecular system of traditional Chinese medicine. ② When soluble calcium salt was used to substitute insoluble SG with GC for co-decocting, a stronger but astigmatic light path appeared than single decocting solution, the zeta potential was reduced, and a large number of accumulated polymers were formed. The results of paste content and conductivity showed that the dissolution of the co-decocting component was reduced than the single decocting component. ITC, UV-vis and IR results showed that there was interaction between GC with Ca²⁺ and SG. The formation of polysink indicated that a large amount of soluble calcium salt would destroy the stability of supramolecular Chinese medicine. The results of ICP-OES and HPLC showed that the glycyrrhizic acid (GA) content of the former lower than the latter, which was related to the formation of a large number of polycondensates with the increase of Ca²⁺ concentration and the decrease of the dissolution of GA and other active ingredients. This study indicates that the compatibility of GC and SG can form a uniform and stable supramolecular system of traditional Chinese medicine. Calcium salt, the main component of SG, is taken as the starting point. Excessive soluble Ca²⁺ can promote the aggregation of active ingredients such as GA, so as to reveal the scientific connotation of the compatibility of GC and SG, an insoluble mineral medicine.

Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution types in patients with perimenopause metabolic syndrome in Guangzhou based on the Stages of Reproductive Aging Workshop+10(STRAW+10),so as to provide a theoretical basis for TCM constitution regulation for patients with PMS.Methods According to the diagnostic criteria of metabolic syndrome,a total of 90 patients with PMS were included.Based on the STRAW+10 staging criteria,the PMS patients were divided into early perimenopause group(-2 phase of STRAW+10,49 cases),late perimenopause group(-1 phase of STRAW+10,24cases),and early postmenopausal group(+la phase of STRAW+10,17 cases).Traditional Chinese Medicine Constitution Classification and Distinguishing Criteria were used to identify the TCM constitution types of all the subjects.At the same time,the Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)were used for scoring anxiety and depression.The distribution of TCM constitution types in patients with different STRAW+10 stages was analyzed,and the SAS and SDS scores of patients with different STRAW+10 stages were compared.Results(1)The primary TCM constitution types in the early perimenopause group(-2 phase of STRAW+10)were yang deficiency constitution(14 cases,29.79％),balanced constitution(10 cases,21.28％),yin deficiency constitution(six cases,12.76％)and blood stasis constitution(six cases,12.76％).In the late perimenopause group(-1 phase of STRAW+10),the primary TCM constitution types were yang deficiency constitution(six cases,25.00％),balanced constitution(four cases,16.66％),blood stasis constitution(four cases,16.66％),qi deficiency constitution(three cases,12.50％)and phlegm-damp constitution(three cases,12.50％).In the early postmenopausal group(+la phase of STRAW+10),the primary TCM constitution types were yang deficiency constitution(seven cases,46.67％),balanced constitution(two cases,13.33％),phlegm-damp constitution(two cases,13.33％),blood stasis constitution(two cases,13.33％),qi deficiency constitution(one case,6.67％)and qi stagnation constitution(one case,6.67％).(2)The SAS score and SDS score in the early perimenopause group(-2 phase of STRAW+10)were(34.55±7.46)points and(35.55±10.61)points,respectively,which were higher than those in the late perimenopause group(-1 phase of STRAW+10)[(33.83±7.73)points and(35.46±11.35)points,respectively]and in the early postmenopausal group(+la phase of STRAW+10)[(35.65±8.67)points and(36.59±12.07)points,respectively].All of the scores were higher than the overall average level.Conclusion The TCM constitution of patients with perimenopause metabolic syndrome is predominated by yang deficiency constitution.The percentage of the balanced constitution gradually decreases with the progression of STRAW+10 staging,and the biased constitutions gradually develop from yin deficiency constitution and blood stasis constitution into qi deficiency constitution and phlegm-damp constitution,and then into phlegm-damp constitution and blood stasis constitution again.With the progression of the stage,the deficiency in the fundamental of the PMS patients becomes more deficient and the pathogens of excess in the incidental also grow.

With the rapid development of the biopharmaceutical industry in China, the laboratory animal sector has entered a stage of rapid growth, and the construction of facility operation systems has become increasingly automated and intelligent. Compared to traditional laboratory animal facilities, new facilities require a more specialized technical team for the maintenance of air supply and exhaust systems, air conditioning, automated control, and the entire barrier system. The Lingang Laboratory’s animal facilities accommodate both large and small animals for feeding and experimental purposes. The facility management team has summarized daily maintenance experiences and explored various operational and maintenance modes based on the characteristics of laboratory operation. After analyzing the advantages and disadvantages of three common modes, this paper provides new ideas for the management of these laboratory animal facilities, and offers guidance for peers in choosing the most appropriate professional maintenance mode.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

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 effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation,the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated.Methods:Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023,42 cases among which were included in the infection-positive group,and 30 cases in the suspected infection group.Forty-two donors un-vaccinated against SARS-CoV-2,un-infected,and donated three consecutive apheresis platelets from October to November 2022 were included in the control group.The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before(Time1)and after(Time2 and Time3)the onset of symptoms,three consecutive times(Time1,Time2,Time3)in the control group by repeated measures analysis of variance.The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not.Results:Simple effect of the number times of tests in the positive and suspected infection groups was significant(Finfection-positive group=6.98,P＜0.001,partial η2=0.79,Fsuspected infection group=4.31,P＜0.001,partial η2=0.70).The positive group and the suspected infection group had lower RBC,HCT,and HGB,and higher PLT and PCT at Time2 compared to Time1 and Time3(P＜0.05).The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2(P＜0.001).The simple effect of the number times of tests in the control group was not significant(F=0.96,P=0.55,partial η2=0.34).The difference of the whole blood count parameters in the control group for three times was not statistically significant(P＞0.05).We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not.The equation had an eigenvalue of 0.22,a canonical correlation of 0.43(x2=27.81,P＜0.001),and an analysis accuracy of 72.9％.Conclusion:The hematological indicators of RBC,HCT,HGB,PLT,PCT,RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes.The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.