ObjectiveTo observe the influence and therapeutic effect of quercetin on cuproptosis in rheumatoid arthritis rats and to explore its possible mechanism based on the solute carrier family 31 member 1 （SLC31A1）/ferredoxin 1 （FDX1） pathway. MethodsSixty male SD rats were divided into six groups： A control group， a model group， high- and low-dose quercetin groups （150 and 50 mg·kg^-1）， a cuproptosis inhibitor （tetrathiomolybdate， TTM） group （10 mg·kg^-1）， and a methotrexate group （2 mg·kg^-1）， 10 rats in each group. Except for the control group， the model of rheumatoid arthritis （CIA） rats was established by type Ⅱ collagen induction method. After successful modeling， each drug group was intervened according to the corresponding dose of drugs， and the control group and the model group were given the same amount of normal saline by gavage， once a day， which lasted for 4 weeks. The swelling degree of rats' feet was observed， and the clinical arthritis scores were determined. The levels of serum rheumatoid factor （RF）， matrix metalloproteinase-3 （MMP-3）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and ceruloplasmin （Cp） were detected by enzyme-linked immunosorbent assay （ELISA）. The content of copper ion （Cu）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） in joint tissue was detected. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of joint tissue. The levels of reactive oxygen species （ROS） and dihydrolipoic acid transacetylase （DLAT） were detected by immunofluorescence （IF）. The protein and mRNA expression of SLC31A1， FDX1， lipoic acid synthase （LIAS）， heat shock protein 70 （HSP70）， pyruvate dehydrogenase E1 subunit β （PDHB）， and copper transporting P-type ATPase β （ATP7B） was detected by immunohistochemistry （IHC） and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared to the control group， the model group exhibited joint swelling and deformity， significantly increased clinical arthritis scores， obvious bone destruction， synovial hyperplasia， and inflammatory cell infiltration in joint tissue. In addition， the serum levels of RF， MMP-3， TNF-α， IL-1β， and Cp showed significant elevation， while the level of IL-10 was significantly reduced. The levels of Cu， MDA， ROS， and DLAT in joint tissue were markedly increased， whereas SOD and GSH content was significantly decreased. The protein and mRNA expression of SLC31A1 and HSP70 was significantly up-regulated， while the protein and mRNA expression of FDX1， LIAS， PDHB， and ATP7B was significantly down-regulated （P<0.01）. Compared to the model group， each treatment group exhibited varying degrees of improvement in joint swelling and deformation as well as clinical arthritis scores in rats. Additionally， there was a reduction in joint bone destruction， inflammatory cell infiltration， and synovial hyperplasia in rats. Furthermore， the serum levels of RF， MMP-3， TNF-α， IL-1β， and Cp significantly decreased， while the level of IL-10 increased significantly. In joint tissue， the levels of Cu， MDA， ROS， and DLAT showed significant decreases， while SOD and GSH content exhibited significant increases. The protein and mRNA expression of SLC31A1 and HSP70 was down-regulated， while the protein and mRNA expression of FDX1， LIAS， PDHB， and ATP7B was up-regulated （P<0.05）. ConclusionQuercetin effectively reduces synovial hyperplasia and inflammatory infiltration in rats with rheumatoid arthritis， thereby alleviating pathological damage to joint tissue. This effect may be attributed to the blockade of the SLC31A1/FDX1 signaling pathway activation and inhibition of excessive cuproptosis.

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

Objective To analyze the clinical efficacy and safety of glecaprevir/pibrentasvir in the treatment of pa-tients with hepatitis C virus(HCV)and human immunodeficiency virus(HIV)co-infection,and provide scientific basis for clinical treatment.Methods 89 initially treated non-cirrhotic patients with HCV/HIV co-infection in a hospital of Butuo County of Liangshan Prefecture from January 2021 to January 2022 were selected.All patients re-ceived glecaprevir/pibrentasvir treatment for 8 weeks and were followed up for 12 weeks.Virological response rate at the end-of-treatment and sustained virological response rate after 12 weeks(SVR12)of treatment as well as oc-currence of adverse reaction were recorded.Results Among 89 initially treated non-cirrhotic patients with HCV/HIV co-infection,most were middle-aged and young married men(n=79,88.8％).HIV was mainly transmitted through sexual contact(n=62,69.7％)and intravenous drug use(n=27,30.3％).The most common HCV geno-types were genotype 1b(n=33,37.1％)and genotype 3b(n=25,28.1％).All patients completed 8 weeks of treatment successfully and HCV RNA load at the end of treatment was below the detection limit(＜25 IU/mL).Eight patients failed to complete the follow-up,and the remaining 81(100％)patients achieved a sustained virologic re-sponse.There were no serious adverse reactions during the observation period,but 11 patients had mild adverse re-actions.Conclusion The 8-week treatment regimen of glecaprevir/pibrentasvir for non-cirrhotic patients with geno-type 1,3,and 6 HCV/HIV co-infection can achieve 100％SVR12,with high safety and tolerability,which can be used as a good choice for clinical treatment of these patients.

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.
Rats ; Animals ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; COVID-19 ; Lignans

Objective　To provide a data foundation not only for food safety supervision and pollution source tracing, but also for the clinical treatment of drug-resistant bacteria in barreled drinking water, the drug resistance and type Ⅲ secretion system (T3SS) virulence genes carriage of Pseudomonas aeruginosa detected in barreled drinking water in Hainan Province were investigated, and the correlative relationship between strain ribosomal subtypes and virulence genes were then discussed. Methods The drug resistance of the isolated 55 strains of Pseudomonas aeruginosa was confirmed by using VITEK 2 Compact automatic microbial drug sensitivity system, and the T3SS virulence genes ExoU, ExoS, ExoT and ExoY were amplified by PCR, bacterial strain subtypes and homology were analyzed by the RiboPrinter automatic microbial gene fingerprint identification system. Results The drug sensitivity results showed that Pseudomonas aeruginosa isolated from barreled water had relatively low drug resistance, though one strain of multidrug-resistant Pseudomonas aeruginosa was discovered, resistant to imipenem, ciprofloxacin and cefepime. The distribution of T3SS virulence genes showed four genotypic combinations: ExoT+/ExoY+/ExoS+/ExoU- (45.45%, 25/55), ExoT+/ExoY+/ExoS-/ExoU+ (34.55%, 19/55), ExoT+/ExoY-/ExoS-/ExoU+(18.18%, 10/55), ExoT+/ExoY+/ExoS+/ExoU+ (1.82%, 1/55). Ribosomal typing results showed that the Pseudomonas aeruginosa strains were divided into six subtypes, the numbers of each subtype accounted for 24 (43.64%), 1 (1.82%), 25 (45.45%), 1 (1.82%), 3 (5.45%) and 1 (1.82%) respectively, with subtype Ⅰ and subtype Ⅲ being dominant. The main T3SS genotypes of the top two subtype I and subtype III were ExoT+/ExoY+/ExoS-/ExoU+ (16/24, 66.67%) and ExoT+/ExoY+/ExoS+/ExoU- (22/25, 88%). Conclusions The T3SS secretion system exhibits the characteristics of multiple virulence genes' coordinated expression, and there is a certain correlation between subtypes of bacterial strains and virulence genotypesThe exploration of the relationship between them provides guidance for tracing the source of Pseudomonas aeruginosa contamination, production control, clinical treatment in barrelled drinking water, and preliminarily establishes the initial data of local Pseudomonas aeruginosa strains in barrelled drinking water as well the related drug sensitivity data in Hainan.

Abstract： Objective　To analyze the changes of cytokine levels in patients with sensitive pulmonary tuberculosis and drug-resistant pulmonary tuberculosis before and after anti-tuberculosis treatment. Methods　The clinical data of 213 pulmonary tuberculosis patients admitted to the Eighth Affiliated Hospital of Xinjiang Medical University from August 2019 to October 2020 were collected, and divided into a sensitive pulmonary tuberculosis group and a drug-resistant pulmonary tuberculosis group, of which 141 were in the sensitive group and 72 in the drug-resistant group , and the pro-inflammatory factors tumor necrosis factor-α (TNF-α), IL-6, IL-17, interferon-γ (IFN-γ) and anti-inflammatory factors IL-10 and IL-4 in plasma before treatment, 3 months and 6 months after treatment were compared. Results　Compared with the healthy group, the levels of plasma IL-6 in the sensitive group and the resistant group were significantly increased, difference was statistically significant (P<0.01). The plasma levels of IFN-γ and IL-17 in the sensitive group were increased, and the difference was statistically significant (P<0.05). Compared with before treatment, the levels of IL-6 and IL-4 in the plasma of the sensitive group after 6 months of treatment were lower than those after 3 months of treatment, and the difference was statistically significant (P<0.05), and IFN-γ was significantly decreased (P<0.001). After 6 months of treatment, the IL-10 content was lower than that before treatment, and the difference was statistically significant (P<0.05), and the IFN-γ decreased significantly (P<0.000 1). The levels of IFN-γ at 3 months were higher than those in the resistant group, and the difference was statistically significant (P<0.01). After 6 months of treatment, there was no significant difference in the content of IFN-γ between the sensitive group and the resistant group. The effective rate of CT absorption was 70% in the sensitive group and only 43.33% in the resistant group at 3 months of treatment, and there was no significant difference in the effective rate between the two groups after 6 months of treatment. Conclusions　Detection of pro-inflammatory cytokines and anti-inflammatory cytokines in plasma can provide reference for host-directed therapy of pulmonary tuberculosis. Understanding this important feature of cytokines on pathogen-host interactions can provide new insights into the study of virulence mechanisms and may provide new approaches for immune intervention in pulmonary tuberculosis.

ObjectiveTo observe that effect of Ersi decoction on rats with rheumatoid arthritis （RA） induced by using the complete Freund's adjuvant emulsion containing bovine type Ⅱ collagenand and elucidate underlying menchanisms involving to inhibit inflammation and joint synovial angiogenesis. MethodThe rat model of RA was established by immune induction with complete Freund's adjuvant emulsion containing bovine type Ⅱ collagen. All male SD rats were randomly divided into blank group， RA model group， methotrexate group（1.0 mg·kg^-1）， and low-， medium- and high-dose group（30，15，7.0 g·kg^-1·d^-1）of Ersi decoction， with 8 rats in each group. Except the blank group， rats in the methotrexate group and Ersi decoction groups were given corresponding doses of methotrexate and Ersi decoction after establishment of RA induced by strengthen immunity，respectively，and those in the model group and blank group received normal saline of equivalent volume，once a day for 28 days. After the administration， the degree of joint swelling of rats in each group was analyzed by joint swelling volume and index. The small animal ultrasound imaging system was used to detect the score and area of synovial hyperplasia of knee joint in right lower limb of rats and hematoxylin-eosin（HE）staining to observe the histomorphological changes in joint synovium of rats. The levels of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） were measured by enzyme-linked immunosorbent assay（ELISA）. Immunohistochemistry was employed to analyze the expression of CD31 and vascular endothelial growth factor receptor 2（VEGFR2） in in joint synovium. ResultCompared with the blank group， the model group demonstrated significant increase in joint swelling volume and index， inflammatory cytokines including TNF-α and IL-1β in serum， the score and area of synovial hyperplasia of knee joint in right lower limb， obvious pathological changes in the synovium and the expression of CD31 and VEGFR2 in joint synovium. Medium and high-dose Ersi decoction significantly alleviated the pathological changes of synovium tissue， attenuated joint swelling volume and index and decreased the expression of CD31 and VEGFR2 in joint synovium as compared with the model group. Moreover， high-dose Ersi decoction showed significantly lower levels of TNF-α and IL-1β in serum， and the score and area of synovial hyperplasia of knee joint in right lower limb. But medium-dose Ersi decoction only showed lower levels of TNF-α and area of synovial hyperplasia of knee joint. ConclusionErsi decoction could reduce synovial inflammation and hyperplasia through inhibiting synovial angiogenesis in rats with RA induced by bovine type Ⅱ collagen for achieving the effect of reducing RA joint damage， which provides an important reference for anti-RA of Ersi decoction in clinical application.

OBJECTIVES: To study the association between oppositional defiant disorder (ODD) and parenting style in children with attention deficit hyperactivity disorder (ADHD). METHODS: A case-control study was performed on 482 children with ADHD, among whom 322 did not have ODD (simple ADHD group) and 160 had ODD (ADHD+ODD group). General demographic data and the Parenting Style Scale assessment scores were collected from the two groups. A multivariate logistic regression analysis was used to identify the association between parenting style and ODD in children with ADHD. RESULTS: There was no significant difference in parenting style scores (including rejection factor, emotional warmth factor, overprotection factor, and preference factor) and general demographic data between the simple ADHD and ADHD+ODD groups (P>0.05). Among the children with the predominantly inattentive type of ADHD, the older the child or the lower the father's educational level, the higher the risk of ODD (P<0.05), while there was no significant association between parenting style and the development of ODD (P>0.05). CONCLUSIONS Parenting style is not significantly associated with the development of ODD in children with ADHD. In clinical practice, it is necessary to eliminate the stereotype that the parents of children with ADHD and comorbid ODD have a poor parenting style and look for the causes of development of ODD from multiple perspectives, so as to provide reasonable intervention recommendations.
Attention Deficit Disorder with Hyperactivity ; Attention Deficit and Disruptive Behavior Disorders ; Case-Control Studies ; Child ; Comorbidity ; Humans ; Parenting ; Parents