OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Objective:To analyze the effect of deep brain electrical stimulation therapy on Parkinson's disease patients with frozen gait and explore its prognostic factors.Methods:A retrospective study was conducted on 86 Parkinson's disease patients with frozen gait admitted to our hospital from January 2020 to December 2022.All patients received deep brain electrical stimulation therapy.Conduct a 2-year outpatient follow-up for all patients,and analyze the scores of the Parkinson's Disease Rating Scale Part 2(UPDRS Ⅱ),Parkinson's Disease Rating Scale Part 3(UPDRS Ⅲ),Fugl Meyer Lower Limb Motor Function Assessment Scale(FMA),and Schwab&England Daily Activity Scale(S&E)before and after medication opening and closing,6 months after surgery,1 year after surgery,and 2 years after surgery.And based on the 2-year follow-up results of the patients,the prognosis level of the patients was evaluated according to the S&E score during drug closure.60 patients with drug closure S&E score＞70 were divided into a good prognosis group,and 26 patients with drug closure S&E score≤70 were divided into a poor prognosis group.Logistic regression model was used to analyze the influencing factors of deep brain electrical stimulation therapy in Parkinson's disease gait freezing patients.Results:At 6 months,1 year,and 2 years after surgery,the UPDRS Ⅱ and UPDRS Ⅲ scores of all patients were lower than those before surgery(P＜0.05).The UPDRS Ⅱ and UPDRS Ⅲ scores of patients before surgery,6 months,1 year,and 2 years after surgery were lower than those of patients before surgery(P＜0.05);At 6 months,1 year,and 2 years after surgery,the FMA and S&E scores of all patients were higher than those before surgery(P＜0.05).There was no significant difference in the FMA and S&E scores between 6 months,1 year,and 2 years after surgery(P＞0.05).However,the FMA and S&E scores at 6 months,1 year,and 2 years after surgery were lower than those at the end of surgery(P＜0.05);There was no significant difference between the gender,BMI,combined underlying disease,levodopa equivalent dose,preoperative UPDRSⅢ score before the on and off periods,and FMA scores before the on and off periods(P＞0.05),Age,Parkinson's disease stage,preoperative UPDRS Ⅱ score between open and off period,and preoperative S&E score between the good prognosis and off prognosis groups(P＜0.05);The UPDRS Ⅱ score(95％CI:1.353～5.782,OR value:2.462),S&E score(95％CI:1.658～4.687,OR value:2.789),and S&E score(95％CI:1.265～6.879,OR value:3.645)before opening surgery are independent influencing factors on deep brain electrical stimulation therapy in Parkinson's disease gait freezing patients(P＜0.05).Conclusion:Deep brain electrical stimulation therapy can improve the condition and motor function of Parkinson's disease patients with frozen gait,but some patients may have poor prognosis due to the influence of UPDRS Ⅱ score before surgery and S&E scores during the opening and closing phases.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.

AIM To investigate the clinical effects of Cinobufosin Injection combined with RALOX-HAIC regimen on patients with hepatocellular carcinoma.METHODS Ninety-two patients were randomly assigned into control group(46 cases)for intervention of RALOX-HAIC regimen,and observation group(46 cases)for intervention of both Cinobufosin Injection and RALOX-HAIC regimen.The changes in short-term effects,survival situation,inflammatory indices(LCN2,NLRP3 inflammasome,NLR,PLR),immune indices(NK cells,CD8+T cells,IL-17,Th17/Treg)and incidence of toxic and side effects were detected.RESULTS Based on mRECIST,the observation group demonstrated higher disease control rate and objective remission rate than the control group(P＜0.05),along with lower disease progression(P＜0.05).After the treatment,the two groups displayed decreased inflammatory indices,IL-17,Th17/Treg(P＜0.05),and increased NK cells,CD8+T cells(P＜0.05),especially for the observation group(P＜0.05).The observation group exhibited lower incidence of abdominal pain,nausea,vomiting,diarrhea,leukopenia and thrombocytopenia than the control group(P＜0.05),and no significant differences in overall survival and incidence of other toxic and side effects were found between the two groups(P＞0.05).CONCLUSION For the patients with hepatocellular carcinoma,Cinobufosin Injection combined with RALOX-HAIC regimen can safely and effectively enhance body immune functions,and reduce in vivo immune indices.

Objective:To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA.Methods:A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children′s Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00).Results:There was a statistically significant difference in the gender and age distribution between the two groups of children ( P<0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes ( P> 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children′s samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β; production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. Conclusion:DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, causing a significant socioeconomic burden. This article reviews the effects of influenza vaccination on COPD and finds that influenza vaccine can significantly reduce the risk of influenza infection, reduce the number of acute exacerbations, and reduce the hospitalization rate in patients with COPD. The vaccine has a favorable safety profile and significant economic benefits, which can reduce medical costs. Currently, influenza vaccination mainly faces challenges such as insufficient patient awareness, insufficient support from the medical system, and socio-cultural and economic factors. Efforts should be focused on reducing the acute exacerbation of COPD patients and providing a scientific basis for the prevention and management of COPD patients.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*