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

AIM:To analyze the clinical phenotypes and genotypes of children with incontinentia pigmenti(IP)and enhance clinicians' understanding of the condition.METHODS: A family with IP diagnosed in February 2020 at the ophthalmology department of People's Hospital of Ningxia Hui Autonomous Region was enrolled. The proband and family members underwent comprehensive systemic and ocular examinations. Peripheral venous blood was collected for DNA extraction, followed by whole-exome sequencing and MLPA assay to identify pathogenic variants. Corresponding treatments were administered based on the severity of fundus lesions, and ocular clinical features and therapeutic outcomes were monitored during follow-up.RESULTS: The child in this study was a female, aged 8 years, with typical skin changes and scarring alopecia and dental abnormalities at the time of initial consultation. The results of genetic testing suggested that the child carried a heterozygous deletion of exons 4-10 of the IKBKG gene chrX:153440010-153446570del. The child had asymmetric lesions in both eyes, with severe lesions in the left eye, atrophy of the eyeballs, and ocular B-ultrasound suggesting structural disturbances in the eye, and neovascularization was seen in the peripheral retina of the right eye, and the patient was given laser photocoagulation treatment for the right eye, and no progression of retinopathy was detected during follow-up.CONCLUSION:Children with IP have different ocular clinical phenotypes, and retinal vasculopathy is the main change. Early screening and timely and standardized treatment are crucial for children diagnosed with IP.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
Lupus Erythematosus, Systemic/immunology* ; Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Pharmacy practice in e-hospital is an innovative form that greatly enhances the accessibility,efficiency,and convenience of medical services,providing continuous health management and chronic disease drug treatment management for patients.To ensure the quality of pharmacy practice in e-hospitals,the standard formulation team for pharmacy practice in e-hospitals adhered to the principles of scientific,universal,instructive,and operability.They comb through key management content from national policy documents,domestic and international standards and regulations,and literature analysis.Combined with the actual work situation of pharmacy practice in e-hospitals,the standard is formulated through multiple rounds of opinion collection and expert verification.This paper interprets the key content of the standard,including basic requirements,service content and processes,and quality management and evaluation improvement,to provide guidance and reference for managers and pharmacists to deeply understand the standard and further enhance the quality of pharmacy practice in e-hospitals.

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 study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]