Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Objective:To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5.Methods:It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas.Results:A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95% CI 1.77-3.56, P<0.001), hypertension ( OR=5.88, 95% CI 1.57-22.10, P=0.009), and diabetes ( OR=4.66, 95% CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95% CI 3.64-11.36, P<0.001) and hypertension ( OR=6.09, 95% CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female ( OR=0.23, 95% CI 0.07-0.72, P=0.011), age (every 10 years increase, OR=3.90, 95% CI 2.42-6.29, P<0.001), diabetes ( OR=5.37, 95% CI 2.19-13.19, P<0.001) and serum magnesium ( OR=0.01,95% CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions:The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.

Objective:To investigate the effect of Qingjin Huazhuo Decoction combined with conventional western medicine on blood hypercoagulability in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) of phlegm-heat stasis lung syndrome.Methods:Randomized controlled trial. According to random number table method, allocation of cases in the observation and control groups. From April 2021 to March 2022, 66 hospitalized patients with AECOPD of phlegm-heat stasis and lung syndrome were randomly divided into control group ( n=32) and study group ( n=34). The control group was treated with conventional western medicine. The study group was treated with Qingjin Huazhuo Decoction on the basis of the control group. Both groups were treated for 7 days. Plasma thrombomodulin (TM), thrombin-antithrombin complex (TAT), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC), plasmin-antiplasmin complex (PIC), prothrombin time (PT), partial thromboplastin time (APTT) and D-dimer levels were measured by automatic immunoassay analyzer; serum TNF-α levels were measured by ELISA and CRP levels were measured by immunoturbidimetry. Adverse reactions and acute thrombotic events during treatment were recorded. Results:During the treatment period, 4 of 66 patients had hemolysis, 2 were mistakenly included in the withdrawal study, 28 in the final control group and 32 in the study group were included for the analyses. After treatment, plasma t-PAIC [(6.19±1.93) μg/L vs. (7.42±2.71) μg/L, t=2.04] level in study group was significantly lower than that of the control group ( P<0.05), and the serum TNF-α [(71.15±25.25) ng/L vs. (122.60±98.76) ng/L, t=2.42] level was significantly lower than that of the control group ( P<0.05), plasma PT [(11.98±0.74) s vs. (11.55±0.77) s, t=-2.19] was significantly longer than that of the control group ( P<0.05). No thrombotic events occurred during hospitalization in the study group, and 1 case of acute myocardial infarction occurred in the control group. Conclusion:Qingjin Huazhuo Decoction combined with conventional western medicine therapy can improve the blood hypercoagulability of AECOPD patients with phlegm-heat stasis lung syndrome.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: To characterize the incidence density of systematic lupus erythematosus (SLE) in Yinzhou District of Ningbo from 2016 to 2021, and compare the age and gender specific differences. Methods: A retrospective cohort study was conducted based on the related data from 2015 to 2021 collected from the Health Information Platform of Yinzhou. Suspected SLE cases in local residents were identified by fuzzy matching of International Classification of Diseases 10^th edition code "M32" or Chinese text "lupus". The classification criteria from Systemic Lupus International Collaboration Clinics-2012 and The European League Against Rheumatism/American College of Rheumatology-2019 were used for case verification. SLE cases were identified with specific algorithm based on verification results, and new cases were identified with 1 year as the washout period. The incidence density and 95%CI were estimated by Poisson distribution. Results: From 2016 to 2021, a total of 1 551 921 permanent residents were registered in Yinzhou, in whom 51.52% were women. The M(Q₁,Q₃) age at enrollment was 40.38 (27.54, 53.54) years. The M(Q₁,Q₃) of follow-up person-years was 3.83 (0.41, 5.83) years. There were 451 new SLE cases, in which 352 were women (78.05%). The 6-year incidence density was 8.14/100 000 person-years (95%CI: 7.41/100 000 person-years-8.93/100 000 person-years) for the total population, 3.68/100 000 person-years (95%CI: 2.99/100 000 person-years-4.48/100 000 person-years) for men and 12.37/100 000 person-years (95%CI: 11.11/100 000 person-years- 13.73/100 000 person-years) for women. The incidence density in men appeared a small peak at 20-29 years old, and began to increase with age from 40 years old. The incidence density in women was highest in age group 20-29 years (16.57/100 000 person-years) and remained to be high until 30-79 years old. The incidence density of SLE in Yinzhou show no significant temporal trend from 2016 to 2021 (men: P=0.848; women: P=1.000). Conclusions: The incidence density of SLE in Yinzhou from 2016 to 2021 was similar to those of other areas in China. SLE has a high incidence in women, especially in the young and elderly, suggesting that more attention should be paid to the diagnosis and treatment of SLE in women.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Asian People ; Incidence ; Lupus Erythematosus, Systemic/diagnosis* ; Retrospective Studies ; China/epidemiology*

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

The diagnosis of nonalcoholic fatty liver disease (NAFLD) is an exclusionary diagnosis, and the name does not reflect the disease’s nature or mechanism. Internationally, MAFLD (metabolic dysfunction-associated fatty liver disease) and MASLD (metabolic dysfunction-associated steatotic liver disease) have recently been proposed, which are translated as metabolic dysfunction-associated fatty liver disease in Chinese. The new name reflects the initiating factors of the disease, its occurrence and development process, and the clinical significance of associated outcomes. Through interventions against metabolic disorders, liver disease (hepatic manifestations of systemic disease) reflecting MASLD (MAFLD) has the potential to improve clinical outcomes.

We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague-Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS.
Animals ; Chronic Pain ; Cytokines/metabolism* ; Fibrosis ; Humans ; Inflammation/metabolism* ; Male ; NF-kappa B/metabolism* ; Pelvic Pain/pathology* ; Prostatitis/metabolism* ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; Syndrome

Concerns has been raised in improving the quality of adaptive design randomized trials reports. Based on the CONSORT 2010 (Consolidated Standards of Reporting Trials), The Adaptive designs CONSORT Extension (ACE) has developed items and reporting specifications for adaptive design trials. This paper presents a brief explanation of the extension and new items of ACE and introduces the applications of ACE checklist with examples.
Checklist ; Humans ; Randomized Controlled Trials as Topic ; Research Design ; Research Report

Pharmacogenetic studies are designed to investigate the associations between genetic variation and treatment response for a particular drug in terms of both efficacy and adverse events and have high sample size requirements. To improve the quality of pharmacogenetic studies and facilitate the Meta-analyses to investigate statistically significant associations, Strengthening the Reporting of Pharmacogenetic Studies (STROPS) guideline was developed in 2020 based on the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. The objective of this article is to present a brief introduction to the STROPS guideline and an interpretation of the key points in some items with examples for the better understanding and application.
Genetic Association Studies ; Humans ; Pharmacogenomic Testing ; Research Report