Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 83
Filter
1.
BMC Psychol ; 12(1): 256, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720387

ABSTRACT

BACKGROUND: The reliability and validity of the current scale for measuring childhood abuse in China are worrying. The development of the Short Version of the Childhood Abuse Self Report Scale (CASRS-12) helps to change this situation, but the effectiveness of the tool has not yet been tested in Chinese participants. This study aims to test the reliability and validity of the CASRS­12 in Chinese college students. METHODS: A total of 932 college students were investigated, of whom 418 were investigated for the first time, and only the CASRS­12 was filled out. In the second survey, 514 participants filled out the CASRS­12, Depression Scale, Self-esteem Scale and Subjective Well-being Scale in turn. After 4 weeks, 109 participants were selected for retest. RESULTS: Each item of the CASRS­12 had good discrimination. Exploratory factor analysis and confirmatory factor analysis (χ2/df = 4. 18, RMSEA = 0. 079, CFI = 0. 95, TLI = 0. 94, IFI = 0. 95, NFI = 0. 94) all supported the four-factor structure of the scale, and the cumulative contribution rate of variance was 76.05%. Cronbach's α coefficient and retest reliability were 0.86 and 0.65, respectively. Childhood abuse was positively correlated with depression (r = 0. 42, p < 0.01), and negatively correlated with self-esteem (r=-0. 33, p < 0.01) and subjective well-being (r=-0. 32, p < 0.01). CONCLUSION: The Chinese version of CASRS­12 meets the measurement standard and could be used to measure the level of childhood abuse of Chinese college students.


Subject(s)
Psychometrics , Self Report , Students , Humans , Female , Male , Reproducibility of Results , Students/psychology , Students/statistics & numerical data , China , Young Adult , Psychometrics/instrumentation , Universities , Adult , Self Concept , Child Abuse/psychology , Child Abuse/statistics & numerical data , Adolescent , Depression/psychology , Depression/diagnosis , Child , Adult Survivors of Child Abuse/psychology , Adult Survivors of Child Abuse/statistics & numerical data , Psychiatric Status Rating Scales/standards , Factor Analysis, Statistical
2.
Nanoscale ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38766844

ABSTRACT

A BiO2-x/COF composite was successfully synthesized by simple mechanical ball milling. Compared to pure BiO2-x and COFs, the BiO2-x/COF composite (1 : 9) showed superior photocatalytic capability. Under visible light irradiation for 90 min, the photocatalytic degradation rate of DCF reached 97%. In addition, the characterization results showed that the formation of heterojunctions and the increase in oxygen vacancy concentration were the reasons for the enhancement of the photocatalytic activity. It is confirmed by free radical capture experiments that ˙O2- and h+ are the main reactive substances in the photocatalytic process. The photocatalytic degradation mechanism of the composite and the photocatalytic degradation pathway of diclofenac were deduced.

3.
Article in English | MEDLINE | ID: mdl-38648756

ABSTRACT

OBJECTIVES: The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and 5 rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across 6 domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level, and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). RESULTS: Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; p < 0.01) and 0.460 (95% CI, 0.227-0.693 p < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all 6 domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language, and exhibited greater comprehensibility, satisfaction, and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. CONCLUSION: ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

4.
Rheumatol Int ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538820

ABSTRACT

OBJECTIVE: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. METHODS: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. RESULTS: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. CONCLUSION: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.

5.
Polymers (Basel) ; 16(4)2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38399917

ABSTRACT

In recent years, the response of new porous materials to visible light and their potential applications in wastewater treatment has received extensive attention from the scientific community. Metal Organic Frameworks (MOFs) and Covalent Organic Frameworks (COFs) have been the focus of attention due to their strong visible light absorption, high specific surface area, well-regulated pore structures, and diverse topologies. In this study, a novel MOF@COF composite with a high surface area, high crystallinity, and structural stability was obtained using the covalent bond formation strategy from COF-JLU19 and NH2-MIL-88B(Fe). Under visible light irradiation, the degradation of tetracycline hydrochloride by this material reached more than 90% within 10 min and was completely degraded within 30 min, which exceeded the degradation rate of individual materials. Remarkably, the catalytic activity decreased by less than 5% even after five degradation cycles, indicating good structural stability. The excellent photocatalytic performance of the NM88(DB)@COF-JLU19 hybrids was attributed to the formation of covalent bonds, which formed a non-homogeneous interface that facilitated effective charge separation and promoted the generation of hydroxyl radicals.

6.
Biomed Pharmacother ; 171: 116195, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38262149

ABSTRACT

Our recent study showed that Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, prevents ovariectomy-induced bone loss by inhibiting osteoclast activity. However, there have been no investigations to determine whether NTZ has preventive potential in other bone resorbing diseases, especially rheumatoid arthritis (RA). In this study, the primary RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) murine model were used to evaluate the effect of NTZ. The results showed that NTZ potently inhibited proliferation, migration and invasion capacity of RA-FLS in a dose dependent manner by restraining cell entry into S phases, without induction of cell apoptosis. NTZ obviously reduced spontaneous mRNA expression of IL-1ß, IL-6 and RANKL, as well as TNF-α-induced transcription of the IL-1ß, IL-6, and MMP9 genes. In terms of molecular mechanism, NTZ significantly inhibited the basal or TNF-α-induced activation of JAK2/STAT3 (T705) and NF-κB pathway, but not MAPK and STAT3 (S727) phosphorylation. Moreover, NTZ ameliorated synovial inflammation and bone erosion in CIA mice through reducing the production of inflammatory mediators and osteoclast formation, respectively. Collectively, our findings indicate that NTZ exhibits anti-inflammatory and anti-erosive effects both ex vivo and in vivo, which provides promising evidence for the therapeutic application of NTZ as a novel therapeutic agent for RA.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Nitro Compounds , Synoviocytes , Thiazoles , Female , Mice , Animals , Synoviocytes/metabolism , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Inflammation/metabolism , Fibroblasts , Cells, Cultured , Synovial Membrane/metabolism
7.
Small ; 20(13): e2304150, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37964398

ABSTRACT

Rheumatoid arthritis (RA), a systemic autoimmune disease, poses a significant human health threat. Iguratimod (IGUR), a novel disease-modifying antirheumatic drug (DMARD), has attracted great attention for RA treatment. Due to IGUR's hydrophobic nature, there's a pressing need for effective pharmaceutical formulations to enhance bioavailability and therapeutic efficacy. The high-gravity nanoprecipitation technique (HGNPT) emerges as a promising approach for formulating poorly water-soluble drugs. In this study, IGUR nanodrugs (NanoIGUR) are synthesized using HGNPT, with a focus on optimizing various operational parameters. The outcomes revealed that HGNPT enabled the continuous production of NanoIGUR with smaller sizes (ranging from 300 to 1000 nm), more uniform shapes, and reduced crystallinity. In vitro drug release tests demonstrated improved dissolution rates with decreasing particle size and crystallinity. Notably, in vitro and in vivo investigations showcased NanoIGUR's efficacy in inhibiting synovial fibroblast proliferation, migration, and invasion, as well as reducing inflammation in collagen-induced arthritis. This study introduces a promising strategy to enhance and broaden the application of poorly water-soluble drugs.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Chromones , Nanoparticles , Sulfonamides , Humans , Polyvinyl Alcohol , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/chemistry , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Water
8.
J Chemother ; 36(3): 179-189, 2024 May.
Article in English | MEDLINE | ID: mdl-37599449

ABSTRACT

Voriconazole (VRC) displays highly variable pharmacokinetics impacting treatment efficacy and safety. To provide evidence for optimizing VRC therapy regimens, the authors set out to determine the factors impacting VRC steady-state trough concentration (Cmin) in patients with various albumin (Alb) level. A total of 275 blood samples of 120 patients and their clinical characteristics and genotypes of CYP2C19, CYP3A4, CYP3A5, CYP2C9, FMO3, ABCB1, POR, NR1I2 and NR1I3 were included in this study. Results of multivariate linear regression analysis demonstrated that C-reactive protein (CRP) and total bilirubin (T-Bil) were predictors of the VRC Cmin adjusted for dose in patients with hypoalbuminemia (Alb < 35 g/L) (R2 = 0.16, P < 0.001). Additionally, in patients with normal albumin level (Alb ≥ 35 g/L), it resulted in a significant model containing factors of the poor metabolizer (PM) CYP2C19 genotype and CRP level (R2 = 0.26, P < 0.001). Therefore, CRP and T-Bil levels ought to receive greater consideration than genetic factors in patients with hypoalbuminemia.


Subject(s)
Antifungal Agents , Hypoalbuminemia , Humans , Voriconazole/adverse effects , Antifungal Agents/adverse effects , Cytochrome P-450 CYP2C19/genetics , Pharmacogenomic Variants , Hypoalbuminemia/genetics , Hypoalbuminemia/chemically induced , Hypoalbuminemia/drug therapy , C-Reactive Protein , Genotype , China
9.
Br J Clin Pharmacol ; 90(2): 440-451, 2024 02.
Article in English | MEDLINE | ID: mdl-37766511

ABSTRACT

AIMS: The aim of this study was to explore the influence and possible mechanisms of pharmacokinetics-related gene polymorphisms, especially CYP2C19 polymorphisms, and non-genetic factors combined with the inflammatory status on the voriconazole (VRC) metabolism of the Chinese population. METHODS: Clinical studies were performed by collecting more than one VRC trough concentration and C-reactive protein (CRP) level. A total of 265 blood samples were collected from 120 patients. RESULTS: Results of multiple regression analyses demonstrated that CYP2C19 genotypes and albumin (Alb) level remained predictors of Cmin ss/D in patients with no to mild inflammation (R2 = 0.12, P < .001). In addition, in patients with moderate to severe inflammation, it resulted in a significant model containing factors of CRP and total bilirubin (T-Bil) levels (R2 = 0.19, P < .001). In non-clinical studies, 32 rats were divided into control and inflammatory groups, and it was found that the mean residence time (MRT(0-t) ) of VRC in the inflammatory group was significantly longer than that in the control group (P < .001), which may be due to down-regulation of mRNA and protein expression of CYP2C19 (CYP2C6 in rats) through interleukin (IL)-6/signal transducer and activator of transcription (STAT) 3 pathway. CONCLUSIONS: Therefore, the effect of CYP2C19 polymorphisms on VRC metabolism may be masked by inflammatory status, which should be of more concern than CYP2C19 polymorphisms in patients with moderate to severe inflammation. Additionally, the impact of Alb and T-Bil on VRC metabolism should not be disregarded.


Subject(s)
Antifungal Agents , Inflammation , Humans , Animals , Rats , Voriconazole/therapeutic use , Antifungal Agents/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Inflammation/drug therapy , China , Genotype
10.
Pharm Res ; 40(10): 2413-2422, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37726405

ABSTRACT

AIMS: Dasatinib, a second-generation tyrosine kinase inhibitor of BCR-ABL 1, used for first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML), exhibits high pharmacokinetic (PK) variability. However, its PK data in Chinese patients with CML remains rarely reported to date. Thus, we developed a population pharmacokinetic (PPK) model of dasatinib in Chinese patients and identified the covariate that could explain the individual variability of PK for optimal individual administration. METHODS: PPK modeling for dasatinib was performed based on 754 plasma concentrations obtained from 140 CML patients and analysis of various genetic and physicochemical parameters. Modeling was performed with nonlinear mixed-effects (NLME) using Phoenix NLME. The finally developed model was evaluated using internal and external validation. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. RESULTS: The PK of dasatinib were well described by a two-compartment with a log-additive residual error model. Patients in the current study had a relatively low estimate of CL/F (126 L/h). A significant association was found between the covariate of age and CL/F of dasatinib, which was incorporated into the final model. None of the genetic factors was confirmed as a significant covariate for dasatinib. The results of external validation with 140 samples from 36 patients were acceptable. Simulation results showed significantly higher exposures in elderly patients. CONCLUSIONS: This study's findings suggested that low-dose dasatinib would be better suited for Chinese patients, and the dosage can be appropriately reduced according to the increase of age, especially for the elderly.


Subject(s)
Antineoplastic Agents , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Aged , Dasatinib/therapeutic use , Pharmacogenetics , East Asian People , Pyrimidines , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein Kinase Inhibitors/therapeutic use
11.
Cancer Chemother Pharmacol ; 92(5): 399-410, 2023 11.
Article in English | MEDLINE | ID: mdl-37624393

ABSTRACT

BACKGROUND: Imatinib is presently the first-line choice for the treatment of chronic myeloid leukemia. However, there are limited real-world data on Chinese patients to support individualized medicine. This work aims to characterize population pharmacokinetics in Chinese patients with chronic myeloid leukemia, investigate the effects of several covariates on imatinib exposure, and provide support for personalized medicine and dose reduction. METHODS: A total of 230 patients with chronic myeloid leukemia were enrolled, and 424 steady-state concentration measurements were taken to perform the population pharmacokinetic analysis and Monte Carlo simulations with Phoenix NLME software. The effects of the demographic, biological, and pharmacogenetic (ten SNP corresponding to CYP3A4, CYP3A5, ABCB1, ABCG2, SCL22A1 and POR) covariates on clearance were evaluated. RESULTS: A one-compartmental model best-described imatinib pharmacokinetics. The hemoglobin and the estimated glomerular filtration rate (< 85 mL⋅min-1⋅1.73 m2) were associated with imatinib clearance. The genetic polymorphisms related to pharmacokinetics were not found to have a significant effect on the clearance of imatinib. The final model estimates of parameters are: ka (h-1) = 0.329; Vd/F (L) = 270; CL/F (L⋅h-1) = 7.60. CONCLUSIONS: Key covariates in the study population accounting for variability in imatinib exposure are hemoglobin and the estimated glomerular filtration rate. There is some need for caution when treating patients with moderate-to-severe renal impairment and significant hemoglobin changes.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid , Humans , Imatinib Mesylate/therapeutic use , East Asian People , Pharmacogenetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
12.
Environ Mol Mutagen ; 64(7): 401-415, 2023 08.
Article in English | MEDLINE | ID: mdl-37522536

ABSTRACT

Individual differences in drug response have always existed in clinical treatment. Many non-genetic factors show non-negligible impacts on personalized medicine. Emerging studies have demonstrated epigenetic could connect non-genetic factors and individual treatment differences. We used systematic retrieval methods and reviewed studies that showed individual factors' impact on DNA methylation of drug metabolism genes. In total, 68 studies were included, and half (n = 36) were cohort studies. Six aspects of individual factors were summarized from the perspective of personalized medicine: parental exposure, environmental pollutants exposure, obesity and diet, drugs, gender and others. The most research (n = 11) focused on ABCG1 methylation. The majority of studies showed non-genetic factors could result in a significant DNA methylation alteration in drug metabolism genes, which subsequently affects the pharmacokinetic processes. However, the underlying mechanism remained unknown. Finally, some viewpoints were presented for future research.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Humans , DNA Methylation/genetics , Diet
13.
J Ethnopharmacol ; 317: 116762, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37301308

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG) is a perennial herb with anti-inflammatory, antibacterial, and antioxidant activities, which is traditionally used to treat inflammation of respiratory tract and gastrointestinal tract, abdominal cramps, bacterial and viral infections. Clinically, it is often used to treat inflammatory-related diseases. Research has shown that the ethanol extract of Scutellaria baicalensis Georgi (SGE) has anti-inflammatory effect, and its main components baicalin and baicalein have analgesic effects. However, the mechanism of SGE in relieving inflammatory pain has not been deeply studied. AIM OF THE STUDY: This study aimed to evaluate the analgesic effect of SGE on complete Freund's adjuvant (CFA)-induced inflammatory pain rats, and to investigate whether its effect on relieving inflammatory pain is associated with regulation of P2X3 receptor. MATERIALS AND METHODS: The analgesic effects of SGE on CFA-induced inflammatory pain rats were evaluated by measuring mechanical pain threshold, thermal pain threshold, and motor coordination ability. The mechanisms of SGE in relieving inflammatory pain were explored by detecting inflammatory factors levels, NF-κB, COX-2 and P2X3 expression, and were further verified by addition of P2X3 receptor agonist (α, ß me-ATP). RESULTS: Our results revealed that SGE can notably increase the mechanical pain threshold and thermal pain threshold of CFA-induced inflammatory pain rats, and markedly alleviate the pathological damage in DRG. SGE could suppress the release of inflammatory factors including IL-1ß, IL-6, TNF-α and restrain the expression of NF-κB, COX-2 and P2X3. Moreover, α, ß me-ATP further exacerbated the inflammatory pain of CFA-induced rats, while SGE could markedly raise the pain thresholds and relieve inflammatory pain. SGE could attenuate the pathological damage, inhibit P2X3 expression, inhibit the elevation of inflammatory factors caused by α, ß me-ATP. SGE can also inhibit NF-κB and ERK1/2 activation caused by α, ß me-ATP, and inhibit the mRNA expression of P2X3, COX-2, NF-κB, IL-1ß, IL-6 and TNF-α in DRG of rats induced by CFA coupled with α, ß me-ATP. CONCLUSIONS: In summary, our research indicated that SGE could alleviate CFA-induced inflammatory pain by suppression of P2X3 receptor.


Subject(s)
NF-kappa B , Receptors, Purinergic P2X3 , Rats , Animals , Freund's Adjuvant , NF-kappa B/metabolism , Ethanol/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Scutellaria baicalensis , Cyclooxygenase 2/metabolism , Pain/chemically induced , Pain/drug therapy , Pain/metabolism , Anti-Inflammatory Agents/adverse effects , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Analgesics/adverse effects , Adenosine Triphosphate
14.
Int J Rheum Dis ; 26(4): 625-637, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36760030

ABSTRACT

OBJECTIVE: We aimed to investigate the effect of targeted therapies on cardiovascular risk in psoriasis (PsO) and psoriatic arthritis (PsA) via a meta-analysis of randomized controlled trials (RCTs). METHODS: Pubmed, Embase, Cochrane Library, and Scopus were searched for RCTs reporting targeted therapies in patients with PsO/PsA published until 28 October 2021. The primary and secondary outcomes included the relationship between targeted therapies and all cardiovascular events (CVEs), major adverse cardiovascular events (MACEs), myocardial infarction (MI), heart failure, and stroke in PsO/PsA. The outcome risk ratios (RRs) were calculated using the Mantel-Haenszel fixed-effect method. RESULTS: A total of 81 articles involving 88 RCTs were included. There was no statistically significant difference regarding the occurrence of all CVEs for all targeted therapies (RR = 1.03, 95% CI 0.74-1.43, P = .85) compared to placebo in PsO/PsA. No statistically significant difference existed between drugs and placebo in patients with PsA on all CVEs (RR = 0.81, 95% CI 0.48-1.36, P = .43). Surprisingly, the incidence of all CVEs was higher in the low dosage group compared to the high dosage group of all targeted therapies (RR = 1.97, 95% CI 1.19-3.27, P = .008) and prominently anti-interleukin-17 agent (RR = 2.20, 95% CI 1.05-4.58, P = .04). CONCLUSION: Current targeted therapies are not associated with the risk of CVEs. Based on the existing evidence, we reported here that a dosage reduction of targeted therapies was not recommended.


Subject(s)
Arthritis, Psoriatic , Myocardial Infarction , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/epidemiology , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Myocardial Infarction/prevention & control , Psoriasis/diagnosis , Psoriasis/drug therapy , Psoriasis/complications , Randomized Controlled Trials as Topic
15.
Paediatr Drugs ; 25(3): 301-319, 2023 May.
Article in English | MEDLINE | ID: mdl-36707496

ABSTRACT

As the activity of certain drug metabolizing enzymes or transporter proteins can vary with age, the effect of ontogenetic and genetic variation on the activity of these enzymes is critical for the accurate prediction of treatment outcomes and toxicity in children. This makes pharmacogenetic research in pediatrics particularly important and urgently needed, but also challenging. This review summarizes pharmacogenetic studies on the effects of genetic polymorphisms on pharmacokinetic parameters and clinical outcomes in pediatric populations for certain drugs, which are commonly prescribed by clinicians across multiple therapeutic areas in a general hospital, organized from those with the most to the least pediatric evidence among each drug category. We also further discuss the research status of the gene-guided dosing regimens and clinical implementation of pediatric pharmacogenetics. More and more drug-gene interactions are demonstrated to have clinical validity for children, and pharmacogenomics in pediatrics have shown evidence-based benefits to enhance the efficacy and precision of existing drug dosing regimens in several therapeutic areas. However, the most important limitation to the implementation is the lack of high-quality, rigorous pediatric prospective clinical studies, so adequately powered interventional clinical trials that support incorporation of pharmacogenetics into the care of children are still needed.


Subject(s)
Pharmacogenetics , Polymorphism, Genetic , Humans , Child , Prospective Studies , Treatment Outcome
16.
Clin Rheumatol ; 42(4): 1137-1150, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36507975

ABSTRACT

OBJECTIVE: This study was conducted to analyse the medication indications of hydroxychloroquine (HCQ) and to explore the clinical characteristics and perinatal outcomes of pregnancy in women with autoimmune abnormalities. The value of HCQ against placental dysfunction-related pregnancy outcomes in people with autoimmune abnormalities was also explored. METHODS: ① To collect HCQ application cases during pregnancy who were hospitalized and delivered from 2016 to 2020. The classification and distribution of HCQ indications were analysed. The characteristics of cases and pregnancy outcomes were discussed. ② To include pregnancy combined with autoimmune abnormalities population during the period. Demographic information, clinical characteristics, classification, medication time frame, and pregnancy outcomes were discussed. RESULTS: ① There were 741 cases of HCQ use during pregnancy. Classification by drug indication was as follows: 257 cases (34.68%) had clear indications for autoimmune diseases. There were 359 controversial cases, as follows: 140 (18.89%) cases of antiphospholipid syndrome and 219 (29.55%) cases of autoantibody-positive cases who had no clear drug indication and also used HCQ during pregnancy. No indications were found for 125 cases (16.87%), without autoimmune abnormalities and empirical medication of HCQ during pregnancy. ② In 853 pregnancies with autoimmune abnormalities, women with systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease had clear indications for HCQ. The proportions of HCQ applied during pregnancy were 86.67%, 85.71%, 73.53%, and 75.00%. The start of medication before pregnancy only accounted for 74.44%, 65.31%, 64.71%, and 43.38%. ③ Medication indicated antiphospholipid syndrome and simple autoantibody-positive cases in the controversial population. The proportions of cases in which HCQ was used during pregnancy were 74.47% (140/188) and 64.79% (219/338). Application of HCQ during pregnancy significantly reduced pre-eclampsia (19.8% vs. 8.91%, P < 0.001), early-onset pre-eclampsia (7.78% vs. 2.51%, P = 0.007), and pregnancy loss during the middle and late pregnancy stages (2.99% vs. 0.56%, P = 0.036) in this controversial population. CONCLUSION: Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. The strength of standardized and specialist management are needed in populations with clear HCQ indications. HCQ-indicated controversial population should avoid overdiagnosis and guard against the potential risks of combined anticoagulation and glucocorticoid therapy. The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. HCQ application may alleviate the incidence of adverse pregnancy outcomes in this population. Key Points •The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. •Our work have discovered the unique value of HCQ in improving placental dysfunction diseases in autoimmune abnormal cases, not just in AID such as SLE, SS, UTCD, and RA. •HCQ is a potential drug option for autoimmune abnormalities to improve placental function, by providing synergistic prevention and treatment of these disorders, not just single target of antispasmodic, anti-hypertensive, and circulatory improvement. •Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. However, the strength of standardized and specialist management are needed in populations with clear HCQ indications.


Subject(s)
Antiphospholipid Syndrome , Antirheumatic Agents , Lupus Erythematosus, Systemic , Pre-Eclampsia , Female , Pregnancy , Humans , Hydroxychloroquine/therapeutic use , Antirheumatic Agents/therapeutic use , Antiphospholipid Syndrome/drug therapy , Placenta , Lupus Erythematosus, Systemic/drug therapy , Pregnancy Outcome , Autoantibodies
17.
Rheumatol Int ; 43(2): 293-301, 2023 02.
Article in English | MEDLINE | ID: mdl-36166058

ABSTRACT

Our study aimed to investigate the clinical and radiological features and prognosis of male smoker patients with rheumatoid arthritis (RA). We consecutively enrolled male inpatients with RA who received chest HRCT during hospitalization in Peking University Third Hospital from Jan 1st, 2012 to August 1st, 2021. 154 male patients with RA were eligible for analysis, of whom 76.6% (n = 118) were current smokers or had a history of cigarette smoking. Compared to never-smokers, smoker patients had more respiratory symptoms, including cough (31.4% vs 5.6%, p = 0.002) and sputum production (26.3% vs 2.8%, p = 0.002), and a higher positive rate of rheumatoid factor (RF) (77.6% vs 58.8%, p = 0.030). A higher percentage of smoker patients showed emphysema (45.8% vs 16.7%, p = 0.002) and signs of lung fibrosis (51/54, 94.4% vs 7/13, 53.8%, p < 0.001) in those with interstitial lung disease (ILD, n = 67) on chest HRCT. The overall survival rate was different between smoker and never-smoker patients (p = 0.031), but instead of cigarette smoking, lung fibrosis on HRCT was the risk factor for survival of our patients. In conclusion, male patients with RA who were current smokers or had a history of cigarette smoking presented more respiratory symptoms and a higher positive rate of RF. They also showed more emphysema and signs of lung fibrosis on chest HRCT. Cigarette smoking impacted on the overall survival as a confounding factor in this cohort of male patients with RA.


Subject(s)
Arthritis, Rheumatoid , Cigarette Smoking , Emphysema , Lung Diseases, Interstitial , Pulmonary Fibrosis , Humans , Male , Pulmonary Fibrosis/etiology , Retrospective Studies , Case-Control Studies , Cigarette Smoking/adverse effects , Tomography, X-Ray Computed , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/complications , Prognosis , Emphysema/complications
18.
Diagnostics (Basel) ; 12(12)2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36553149

ABSTRACT

OBJECTIVE: Esophageal dysmotility is a common and neglected complication of systemic sclerosis (SSc) associated with poor prognosis, while the assessment remains a challenge. We aimed to develop a diagnostic model for esophageal dysmotility in SSc patients that provides individualized risk estimates. METHODS: Seventy-five SSc patients who underwent high-resolution manometry (HRM) were included in the study. Esophageal widest diameter (WED) was measured on a chest CT scan. Esophageal parameters between patients with and without esophageal dysmotility were compared. Multivariate logistic regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to fit the model. The diagnostic model was evaluated by discrimination and calibration. Internal validation was estimated using the enhanced bootstrap method with 1000 repetitions. RESULTS: Sixty-one systemic sclerosis patients (81.3%) were diagnosed with esophageal dysmotility according to the Chicago Classification v 3.0. The diagnostic model for evaluating the probability of esophageal dysmotility integrated clinical and imaging features, including disease duration, ILD, and WED. The model displayed good discrimination with an area under the curve (AUC) of 0.923 (95% CI: 0.837-1.000), a Brier score of 0.083, and good calibration. A high AUC value of 0.911 could still be achieved in the internal validation. CONCLUSION: The diagnostic model, which combines the disease duration, ILD, and imaging feature (WED), is an effective and noninvasive method for predicting esophageal dysmotility in SSc patients.

19.
Expert Rev Respir Med ; 16(6): 697-705, 2022 06.
Article in English | MEDLINE | ID: mdl-35687867

ABSTRACT

BACKGROUND: Bronchiectasis was reported in 2%-40% of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), but there were no studies on the prevalence, risk factors and impact of AAV-associated bronchiectasis in Chinese patients. RESEARCH DESIGN AND METHODS: AAV patients were retrospectively enrolled. The clinical, laboratory and imaging features and the prognosis were analyzed and compared between those with and without bronchiectasis. RESULTS: Bronchiectasis was present in 48/212 (22.6%) of our AAV patients, among whom 41 were confirmed in 210 patients (19.5%) who received chest HRCT at the initial diagnosis of AAV. There were more women and fewer smokers in those with bronchiectasis as compared to those without. Cases with positive anti-MPO were more likely to have bronchiectasis (26.2%), and those with bronchiectasis were more likely to be anti-MPO positive (93.8%). Patients who had a diagnosis of bronchiectasis before AAV were more likely to have nervous system involvement, while patients without bronchiectasis had higher 24h proteinuria. The presence of bronchiectasis showed no significant effect on the 1, 3, 5-year survival. CONCLUSIONS: Nearly 20% of patients showed bronchiectasis on chest HRCT at the initial diagnosis of AAV, and positivity of anti-MPO was associated with bronchiectasis in a Chinese cohort of AAV patients.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Bronchiectasis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Antibodies, Antineutrophil Cytoplasmic , Bronchiectasis/epidemiology , Case-Control Studies , Female , Humans , Peroxidase , Prognosis , Retrospective Studies
20.
Clin Breast Cancer ; 22(2): e135-e141, 2022 02.
Article in English | MEDLINE | ID: mdl-34119428

ABSTRACT

BACKGROUND: Breast cancer is the most common malignant tumor in women and is not easy to diagnose. Increasing evidence has underscored that long non-coding RNAs (lncRNAs) play important regulatory roles in the occurrence and progression of many cancers, including breast cancer. We aimed to identify lncRNAs in plasma as potential biomarkers for breast cancer. PATIENTS AND METHODS: We analyzed the Gene Expression Omnibus (GEO) datasets GSE22820, GSE42568, and GSE65194 to identify the common differential genes between cancer tissues and adjacent tissues. Then 14 lncRNAs were identified among the common differential genes and validated by using real-time quantitative polymerase chain reaction in 92 patients with breast cancer and 100 healthy controls. Receiver operating characteristic (ROC) curves were constructed to evaluate their diagnostic value for breast cancer. RESULTS: Integrated analysis of the GEO datasets identified three significantly upregulated and 11 downregulated lncRNAs in breast cancer tissues. Compared with healthy controls, MIAT was significantly upregulated in breast cancer patient plasma, and LINC00968 and LINC01140 were significantly downregulated. ROC curve analysis suggested that these three lncRNAs can discriminate breast cancer from healthy individual with high specificity and sensitivity. CONCLUSION: This research identified three differentially expressed lncRNAs in breast cancer patient plasma. Our data suggest that these three lncRNAs can be used as potential diagnostic biomarkers of breast cancer.


Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/diagnosis , RNA, Long Noncoding/blood , Breast Neoplasms/genetics , Case-Control Studies , Female , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Humans
SELECTION OF CITATIONS
SEARCH DETAIL
...