OBJECTIVE To investigate the impact of cerebral ischemia-reperfusion(CIR)injury on glucuronidation of IMM-H004 in the brain.METHODS IMM-H004,a neuroprotective agent,underwent glucuronidation primarily mediated by uridine diphosphate glucuronosyltransferases(UGT)to form IMM-H004G,which was subsequently hydrolyzed back to IMM-H004 by β-glucuronidase.① Cellular experiments:human glial cells(HEB)and human neuroblastoma cells(SH-SY5Y)cell lines were assigned to two groups:a normal control group and an oxygen-glucose deprivation/reoxygenation(OGD/R)model group.An OGD/R model was established by subjecting the cells to one-hour oxygen-glucose deprivation,followed by reoxygenation.Cell viability was assessed using the methylthiazolyldi-phenyl-tetrazolium bromide(MTT)assay.The mRNA levels of UGT and its regulatory factor,nuclear factor erythroid 2 related factor 2(Nrf2),were measured by real-time fluorescence quantitative PCR(RT-qPCR).The content of IMM-H004G glucuronidated from IMM-H004,and the content of IMM-H004 hydrolyzed from IMM-H004G were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS).② Animal experiments:Male SD rats were randomly assigned to three groups:a normal control group,a CIR model group,and a sham operation group.Rats in the normal control group received no surgical interventions while those in the CIR model group underwent four-vessel occlusion surgery to induce acute CIR injury.Rats in the sham operation group was treated the same way as the CIR model group except for the four-vessel occlusion.The activities of UGT and β-glucuronidase in brain tissues were determined by LC-MS/MS.IMM-H004 was administered via intracerebroventricular injec-tion,and the concentrations of IMM-H004 and IMM-H004G in different regions of the brain were deter-mined using LC-MS/MS to investigate the impact of CIR injury on IMM-H004 metabolism.RESULTS① Cellular experiments:Compared with the control group,OGD/R injury reduced the viability of HEB and SH-SY5Y cells to 72.30%and 53.56%,respectively.In HEB cells,OGD/R injury significantly down-regulated the mRNA expressions of UGT1A1,UGT1A7 and UGT1A8,resulting in a reduction of IMM-H004G production to 50.05%-68.95%of the normal level,while hydrolytic metabolism remained unaf-fected.No significant changes were observed in SH-SY5Y cells.②Animal experiments:CIR injury had no impact on the activity of UGT or β-glucuronidase in rat brain tissues.In addition,the distribution of IMM-H004 and IMM-H004G across different brain regions remained unchanged.CONCLUSION These findings show that OGD/R injury reduces UGT-mediated glucuronidation of IMM-H004,whereas CIR injury does not significantly affect its metabolism in the brain,suggesting the presence of compen-satory mechanisms in brain tissues that help maintain drug homeostasis.

ObjectiveTo investigate the chemical hazards in the production line of lithium batteries, so as to provide a scientific basis for the management of occupational-health risk and to promote the healthy and sustainable development of the lithium battery industry. MethodsAn on-site survey on the process flow of the production of lithium battery was conducted in an enterprise. Volatile organic compounds (VOCs) in the occupational environment were collected by Summa canisters, carbonates and N-methyl pyrrolidone (NMP) were collected using activated carbon tubes, and airborne metals were collected using filter membranes. VOCs, carbonates and NMP were detected by gas chromatography-mass spectrometry (GC-MS), and airborne metal elements in the dust samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). ResultsNon-targeted environmental monitoring results indicated that NMP was detected in the negative /positive electrode coating, assembly and drying filling workstations, dimethyl carbonate (DMC) was detected in the assembly, drying and electrolyte injection workstations, and ethyl methyl carbonate (EMC) was detected solely in the electrolyte injection workstation. Semi-quantitative analyses of VOCs identified 136 pollutants, including acrylonitrile and halohydrocarbons. Quantitative targeted environmental monitoring results revealed the highest geometric mean (GM) concentration of EMC (31.450 mg·m^-3) was found in the assembly and drying workstations, diethyl carbonate (DEC) was detected in all workstations. While vinylene carbonate (VC) and ethylene carbonate (EC) were detected only in electrolyte injection, assembly and drying workstations. NMP was detected in all positive electrode coating samples, with a GM concentration of 5.68 mg·m^-3 (concentration range: 4.0‒ 7.4 mg·m^-³). Lithium was exclusively detected in dust samples from the liquid injection workstation (GM: 0.014 μg·m^-³). ConclusionNMP, EMC, DEC, and other chemicals are identified at the key workstations such as the positive electrode coating, electrolyte injection, assembly and drying in the lithium production line. Furthermore, semi-quantitative VOCs analyses identified 136 pollutants, demonstrating a characteristic of multicomponent chemical exposure.

Objective To analyze the clinical characteristics and interventional treatment effects of pa-tients with renal arteriovenous fistula in this hospital over the past 10 years.Methods A retrospective analy-sis was conducted on the clinical and imaging data of 40 patients with renal arteriovenous fistula who were treated in this hospital from October 2012 to October 2022.After classifying the fistula type using digital sub-traction angiography(DSA),an individualized embolization plan was developed by a vascular surgery team.Postoperatively,the embolization materials,embolization success rate,clinical success rate,perioperative renal function changes and complications were analyzed.Results A total of 29 cases(72.5%)had acquired renal arteriovenous fistula,while 11 cases(27.5%)had non-acquired renal arteriovenous fistula.Forty-three super-selective transcatheter arterial embolization(TAE)procedures were performed,achieving a technical success rate of 100.0%(40/40)and a clinical success rate of 95.0%(38/40).The mean serum creatinine levels after TAE were(91.39±23.72)mmol/L in the non-acquired group and(105.94±35.51)mmol/L in the acquired group.No statistically significant difference was observed in perioperative serum creatinine changes between the two groups(P=0.095).No severe complications such as renal function deterioration occurred postopera-tively in any patient.Conclusion Gross hematuria serves as the primary clinical manifestation of renal arterio-venous fistula,with abdominal pain being more prevalent in non-acquired renal arteriovenous fistula.The em-bolization approach combining coils with polyvinyl alcohol particles demonstrates favorable safety and efficacy in treating renal arteriovenous fistula.

OBJECTIVE To investigate the impact of cerebral ischemia-reperfusion(CIR)injury on glucuronidation of IMM-H004 in the brain.METHODS IMM-H004,a neuroprotective agent,underwent glucuronidation primarily mediated by uridine diphosphate glucuronosyltransferases(UGT)to form IMM-H004G,which was subsequently hydrolyzed back to IMM-H004 by β-glucuronidase.① Cellular experiments:human glial cells(HEB)and human neuroblastoma cells(SH-SY5Y)cell lines were assigned to two groups:a normal control group and an oxygen-glucose deprivation/reoxygenation(OGD/R)model group.An OGD/R model was established by subjecting the cells to one-hour oxygen-glucose deprivation,followed by reoxygenation.Cell viability was assessed using the methylthiazolyldi-phenyl-tetrazolium bromide(MTT)assay.The mRNA levels of UGT and its regulatory factor,nuclear factor erythroid 2 related factor 2(Nrf2),were measured by real-time fluorescence quantitative PCR(RT-qPCR).The content of IMM-H004G glucuronidated from IMM-H004,and the content of IMM-H004 hydrolyzed from IMM-H004G were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS).② Animal experiments:Male SD rats were randomly assigned to three groups:a normal control group,a CIR model group,and a sham operation group.Rats in the normal control group received no surgical interventions while those in the CIR model group underwent four-vessel occlusion surgery to induce acute CIR injury.Rats in the sham operation group was treated the same way as the CIR model group except for the four-vessel occlusion.The activities of UGT and β-glucuronidase in brain tissues were determined by LC-MS/MS.IMM-H004 was administered via intracerebroventricular injec-tion,and the concentrations of IMM-H004 and IMM-H004G in different regions of the brain were deter-mined using LC-MS/MS to investigate the impact of CIR injury on IMM-H004 metabolism.RESULTS① Cellular experiments:Compared with the control group,OGD/R injury reduced the viability of HEB and SH-SY5Y cells to 72.30%and 53.56%,respectively.In HEB cells,OGD/R injury significantly down-regulated the mRNA expressions of UGT1A1,UGT1A7 and UGT1A8,resulting in a reduction of IMM-H004G production to 50.05%-68.95%of the normal level,while hydrolytic metabolism remained unaf-fected.No significant changes were observed in SH-SY5Y cells.②Animal experiments:CIR injury had no impact on the activity of UGT or β-glucuronidase in rat brain tissues.In addition,the distribution of IMM-H004 and IMM-H004G across different brain regions remained unchanged.CONCLUSION These findings show that OGD/R injury reduces UGT-mediated glucuronidation of IMM-H004,whereas CIR injury does not significantly affect its metabolism in the brain,suggesting the presence of compen-satory mechanisms in brain tissues that help maintain drug homeostasis.

Objective:To identify and observe disease-causing gene variants and clinical phenotypes in a Han Chinese family with Leber congenital amaurosis (LCA).Methods:A retrospective study. A patient with LCA10 and his parents who had presented at Department of Ophthalmology of Henan Provincial People's Hospital on May 2022 were selected as the study subject. Detailed medical and family histories were recorded, fundus photography and flash electroretinogram (F-ERG) were performed. Peripheral venous blood samples (3 ml) of the proband and his parents were collected to extract whole genomic DNA, then whole exome sequencing (WES) and mitochondrial DNA (mtDNA) sequencing were carried out for the proband to determine the disease-causing gene and variants. All variants were annotated by bioinformatics analysis. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the pathogenicity of all detected variants were evaluated. Candidate variants were verified by Sanger sequencing, and in vitro minigene assay were performed to evaluate the impact of the missense variant with insufficient evidence on mRNA splicing.Results:The proband, male, 7-month-old, presented with an inability to follow light or objects, eye poking, photophobia, nystagmus, partial loss of retinal pigment epithelium around the fovea of the macula. At the age of 2 years old, F-ERG revealed severe reduction, elongation, or even no waveform of a-wave and b-wave in both eyes. No obvious abnormality was found in the clinical phenotype of his parents. The result of WES revealed that the proband carried two variants in exon 40 and exon 2 of CEP290, a frameshift variant c.5515_5518del (p.Glu1839Lysfs*11) (V1) and a novel missense variant c.74C>T (p.Ala25Val) (V2), respectively. The result of mitochondrial DNA sequencing was negative. Sanger sequencing confirmed that the heterozygous frameshift variant was inherited from his father and the heterozygous novel missense variant was inherited from his mother, which constituted compound heterozygous variants. In vitro minigene splicing assay confirmed that V2 created a new splicing donor at exon 2, leading to the in-frame deletion of 30bp fragment during transcription and loss of 10 amino acid residues in the protein. The two variants were pathogenic (V1) and likely pathogenic (V2) based on ACMG guidelines, respectively. Conclusions:The c.5515_5518del and novel c.74C>T compound heterozygous variants of the CEP290 gene probably are the cause of LCA10 in this family, which lead to the production of a truncated protein and aberrant splicing of pre-mRNA, respectively. LCA is characterized by early onset, severe impairment of visual function, and a wide range of disease-causing variations.

BACKGROUND:Previous animal studies have shown that riluzole can inhibit neuroinflammatory response after spinal cord injury and promote functional recovery in injured rats,but the study on whether it can regulate the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome in the acute stage is lacking. OBJECTIVE:To observe whether riluzole can reduce microglial pyroptosis and promote functional recovery after spinal cord injury by modulating NLRP3 inflammasome through animal experiments,histological experiments and molecular biology experiments. METHODS:Female SD rats were divided into sham operation,model and riluzole groups,with 12 rats in each group.In addition to the sham operation group,T10 spinal cord injury was conducted in rats.The model group was treated with intraperitoneal administration of riluzole with solvent cyclodextrin.The riluzole group was treated with a 4 mg/kg dose of riluzole injection.The effect of riluzole on motor function recovery was assessed using the BBB score and inclined plane test.The recovery of sensory-evoked potential and motor-evoked potential was measured by electrophysiology.Hematoxylin-eosin staining was used to evaluate spinal cord tissue repair.The regulatory effects of riluzole on NLRP3,Caspase-1 and gasdermin D protein expression in spinal cord tissues were detected by western blot assay.ELISA was utilized to detect the expression levels of inflammatory factors interleukin-1β and interleukin-18.The effects of riluzole on the expression of NLRP3,Caspase-1,gasdermin D and interleukin-1β in microglial cells of the injured spinal cord were determined by immunofluorescence staining. RESULTS AND CONCLUSION:(1)At 35 days after spinal cord injury,BBB score and inclined plane test score in the riluzole group were higher than those in the model group(P<0.05).(2)At 3 days after spinal cord injury,the protein expressions of NLRP3,cleaved Caspase-1,gasdermin D-N(N-terminal domain),interleukin-1β,and interleukin-18 in the spinal cord homogenate of the riluzole group were significantly lower than those of the model group(P<0.05).(3)At 3 days after spinal cord injury,the fluorescence intensity of NLRP3,Caspase-1,gasdermin D and interleukin-1β in the riluzole group was significantly lower than that in the model group(P<0.05).(4)At day 35 after spinal cord injury,hematoxylin-eosin staining showed that the area of spinal cord injury in the riluzole group was smaller than that in the model group.Electrophysiological tests showed that the latency periods of sensory-evoked potential and motor-evoked potential in the riluzole group were shorter than those in the model group,and the latency period of wave amplitude in the riluzole group was higher than that in the model group.(5)These results suggest that riluzole can promote the repair of injured spinal cord tissue,promote the repair of nerve conduction function,and further promote the recovery of motor function in rats with spinal cord injury,which may be achieved through the regulation of NLRP3 inflammasome and the reduction of microglial pyroptosis.

By applying "homeostasis" to the study of the meridian and collateral system， the concept of meridian and collateral homeostasis has been proposed which refers to a balanced and stable state of meridian and collateral system， and plays an important role in maintaining body health and can provide a reference for the diagnosis and treatment of diseases. Phenomics realizes the cross-scale correlation from micro-phenotypic data， such as genome， proteome， and metabolome， to macro-phenotypic data， such as physiological state， behavioral activities， and external manifestations. From the perspective of phenomics， this paper proposes a meridian and collateral homeostasis dynamic mapping model of "macroscopic signs and microscopic expression". This model combines macro signs such as the four examinations of traditional Chinese medicine （TCM）， biophysical indicators of acupoints， and micro expression information such as genes， proteins， and metabolism， and systematically investigates the relationship between meridian and collateral homeostasis and health and disease， thereby providing ideas and references for the identification of pre-disease states as well as precise diagnosis and treatment in TCM.

Background Phenolic compounds, which are widely used as plasticizers, antibacterial agents, and preservatives in industrial production, have endocrine disrupting effects on humans. Previous epidemiological studies on the associations between phenolic compound exposure and blood lipids are mainly based on single measurement of spot urine samples, neglecting potential lag effects of phenolic compounds, and the conclusions are inconsistent. Objective To investigate the effects of short-term exposure to phenolic compounds at different lag days on blood lipid levels in adults. Methods We recruited 143 adults (43 males and 100 females) in Wuhan for three consecutive seasonal rounds of repeated visits: summer and autumn rounds of 2017 and winter of 2018. Morning urine samples were collected for four consecutive days during each round. A set of questionnaires were also distributed on the first day. Physical examinations and fasting venous blood sample collection were conducted on the fourth day. A total of 126 adults were included for analysis (340 person-time, 1251 urine samples). The concentrations of six urinary phenolic compounds [bisphenol A (BPA), bisphenol S (BPS), triclosan (TCS), methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP)] were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. Linear mixed-effect models (LMEs), multiple informant models, and generalized linear models were utilized to estimate the associations of urinary phenolic compounds at different lag days with total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and the ratio of TG to HDL-C (TG/HDL-C). Stratified analyses were conducted by selected characteristics. Results After covariate and multiple adjustments, the LMEs indicated that a change in urinary BPA at lag 0 day from the low concentration group (P _FDR<0.05), and this association was more pronounced in men (P _interaction=0.028) and smokers (P _interaction=0.040). In addition, a change in urinary TCS at lag 2 day from the low concentration group (P _FDR<0.05). The positive association of TCS with TG was more evident in subjects aged < 50 years (P _interaction=0.037). No significant associations were found between urinary phenolic compounds at other lag days and blood lipids. Conclusion Short-term exposures to BPA and TCS are positively correlated with unfavorable changes in blood lipids in adults, and the association seem to be more pronounced in men, smokers, or individuals aged < 50 years.

OBJECTIVE To study the effect of 60Co-γ irradiation on the sterilization effect and main components of Rubus chingii Hu. METHODS Irradiated Rubus chingii Hu by 0, 6, 10, 15, 30 kGy doses of 60Co-γ, used the microbial count method to determine the microbial level of Rubus chingii Hu before and after irradiation. Analyzed the components of Rubus chingii Hu by high resolution mass spectrometry, investigated the effects of irradiation on the quality of Rubus chingii Hu by comparing the components of Rubus chingii Hu samples before and after irradiation, analyzing the quantitative results of ellagic acid and kaempferol 3-O-yunxiangoside, and evaluating the similarity of fingerprints. RESULTS The results of microbial examination of Rubus chingii Hu after different doses of irradiation all met the requirements, cluster analysis and principal component analysis of 20 components showed no significant difference. And there was no significant difference in the contents of ellagic acid and kaempferol 3-O-glucoside before and after irradiation. The similarity of fingerprints before and after irradiation was between 0.995 and 1.000. CONCLUSION Irradiation can effectively control the microbial level in Rubus chingii Hu, and there is no significant effect on the chemical composition of Rubus chingii Hu, the results provide a basis for the application of irradiation in the sterilization process of Rubus chingii Hu.

BACKGROUND:Neuroinflammation is an important factor leading to secondary spinal cord injury,and microglia/macrophage pyroptosis is a significant part of post-spinal cord injury neuroinflammation.Studies have shown that microglia/macrophage undergoes pyroptosis after spinal cord injury,but the regulatory mechanism of circular RNA(circRNA)in microglia/macrophage pyroptosis after spinal cord injury remains unclear. OBJECTIVE:To investigate the role and mechanism of circRNA0005512 in regulating microglia/macrophage pyroptosis after spinal cord injury. METHODS:Female Wistar rats were divided into sham group and spinal cord injury group.Motor function was evaluated using the Basso,Beattie,and Bresnahan(BBB)scale.Cavity volume was assessed by hematoxylin-eosin staining.Differential expression of circRNA in spinal cord tissue was screened using RNA-sequencing and circ0005512 was validated by real-time PCR.Immunofluorescence,western blot assay,ELISA,and real-time PCR were performed to detect cell pyroptosis in the rats and lipopolysaccharide-induced microglial cell line HAPI cell models.Gene knockdown was used to confirm the regulatory role of circRNA0005512 in microglia/macrophage pyroptosis. RESULTS AND CONCLUSION:(1)Seven days after spinal cord injury,evident cavities were observed at the injury site.Immediately after spinal cord injury,the motor function of rats was completely lost.Over time,the motor function of rats in the spinal cord injury group gradually partially recovered,and there was a significant difference in BBB scores compared to the sham group.(2)Circ0005512 was significantly upregulated according to the results of the RNA-sequencing and confirmed in both the animal and cell models.(3)Immunofluorescence,western blot assay,real-time PCR,and ELISA confirmed the significant upregulation of cell pyroptosis markers(NLRP3,GSDMD,and caspase-1)in spinal cord injury tissue and lipopolysaccharide-induced HAPI cells.(4)In the cell model,knockdown of circ0005512 resulted in significantly decreased levels of cell pyroptosis marker-NLRP3.(5)The results above indicate that circ0005512 promotes pyroptosis in microglia/macrophages after spinal cord injury.