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 compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures.Methods A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021.Among them,37 patients were treated with F screw internal fixa-tion,including 16 males and 21 females,aged47 to 64years old with an average of(53.87±5.28)years old;According to Pauwels classification,there were 1 case of type Ⅰ,19 cases of type Ⅱ,17 cases of type Ⅲ;8 cases of combined medical diseases;17 cases of falling,8 cases of traffic accident and 12 cases of falling from height;The time from injury to operation was 29 to 49 hours with average of(35.00±7.34)hours.Another 35 cases used internal fixation with an inverted triangle parallel nail,including 13 males and 22 females with an average age of 46 to 63 years old(52.36±5.05)years old;According to the Pauwels injury classifi-cation:there were 2 cases of type Ⅰ,21 cases of type Ⅱ,12 cases of type Ⅲ;6 cases of medical diseases,15 cases of falling in-jury,9 cases of traffic accident,11 cases of falling injury;The time from injury to operation was 30 to 45 hours with an average of(33.00±6.83)h.The intraoperative blood loss,operation time,intraoperative fluoroscopy times,follow-up time,fracture healing time,postoperative complications were observed and compared between the two groups.The hip joint function was e-valuated by Harris score at 6 months and 12 months after operation.Results There was no significant difference in operation time,intraoperative blood loss,intraoperative fluoroscopy times and other intraoperative data between two groups(P＞0.05).Both groups were followed up regularly,and the follow-up time was 12 to 16 months.The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group(P＜0.05).There was 1 case of femoral neck shortening in the F screw internal fixation group,1 case of nonunion,1 case of nail withdrawal,and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group.The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group(P＜0.05).Conclusion Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures.It can significantly shorten the fracture healing time,reduce the incidence of postoperative complications,significantly improve hip joint function,and improve the quality of life.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Abstract: Objective To explore and analyze the diagnostic value of multicolor melting curve analysis (MMCA) for the resistance of five anti-tuberculosis drugs, so as to clarify the clinical value of MMCA in detecting drug resistance of Mycobacterium tuberculosis. Methods From April 2021 to May 2022, 200 patients with positive Mycobacterium tuberculosis admitted to the Fourth People's Hospital of Qinghai Province were selected as research objects, and sputum specimens were taken from the patients. Traditional Mycobacterium tuberculosis drug sensitivity test (modified Löwenstein-Jensen medium method) and MMCA analysis were respectively given to detect the resistance of five anti-tuberculosis drugs, including isoniazid, ethambutol, streptomycin, rifampicin and isoniazid, respectively. Those samples with inconsistent results between the two diagnosis methods were subjected to gene sequencing verification, and the diagnosis efficiency of MMCA for the five anti-tuberculosis drugs was compared. Results Using Mycobacterium tuberculosis drug sensitivity as the gold standard for drug resistance diagnosis, the sensitivity of MMCA for detecting drug resistance of rifampicin, ethambutol, streptomycin, isoniazid and levofloxacin were 95.83% (46/48), 93.75% (15/16), 100.00% (15/15), 100.00% (20/20) and 70.00% (7/10), respectively, with statistical differences between groups (P<0.05). There were no statistically significant differences in the specificity, positive predictive value, negative predictive value and accuracy of MMCA for the five anti-tuberculosis drugs (P>0.05). For the 8 samples with inconsistent results between MMCA and modified Löwenstein-Jensen medium method, gene sequencing was performed and compared with the results of gene sequencing. After comparison with gene sequencing results, it was found that the coincidence rate of MMCA and gene sequencing results was 75.00% (6/8). Conclusions In the detection of drug-resistant mutations in TB patients, multi-color probe fusion curve analysis has high diagnostic efficacy for first-line anti-tuberculosis drugs, but is not sensitive to second-line anti-tuberculosis drug levofloxacin. Therefore, for the detection of first-line anti-tuberculosis drugs, MMCA has a good clinical application prospect.

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.
Rats ; Male ; Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Diet, High-Fat/adverse effects* ; Diosgenin/metabolism* ; Chaperonin 60/therapeutic use* ; Rats, Sprague-Dawley ; Liver ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Triglycerides ; RNA, Messenger/metabolism* ; Simvastatin/therapeutic use* ; Body Weight ; Lipid Metabolism ; Mammals/metabolism*

Child ; Humans ; Hemangioma/surgery* ; Wrist Joint

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 investigate the EMG characteristics and clinical application value of surface EMG in cervical muscle group of children with congenital muscular torticollis(CMT).Methods A retrospective analysis was performed on 478 children diagnosed as CMT from January 2018 to August 2022 in Rehabilitation Center of the Children's Hospital Affiliated to Chongqing Medical University.The torticollis side of the same case was included in observation group and the healthy side was included in control group.Surface EMG was used to record the electromyography root-mean-square values of bilateral sternocleidomastoid muscles,platysma muscles and upper trapezius muscles in the rest and different exercise states.The difference of root-mean-square values between the affected side and the healthy side muscle groups at rest and under different exercise states and the diagnostic value were compared.Spearman correlation analysis was used to evaluate the relationship between the severity of congenital muscular torticollis on the affected side and the root mean square value of each cervical muscle group.Results The root-mean-square value of sternocleidomastoid muscle on the affected side of CMT children was higher than that on the healthy side during relaxation and lower than that on the healthy side during contraction,and the differences were statistically significant(P<0.05),the abnormal root-mean-square value of the affected side in the resting position and in all motion state has higher diagnostic value.The root-mean-square value of platysma muscle on the affected side was higher than that on the healthy side when it was in the resting position and the reverse neck rotation relaxed state(P<0.05),and lower than that on the healthy side when it was in the same neck rotation contraction state(P<0.05),abnormal values detected in resting sitting position and elevation of head have higher value.Root-mean-square value of upper trapezius muscle on the affected side was higher than that on the healthy side in the relaxed state(P<0.05).The abnormal values in sitting position,turning neck and bending head have high diagnostic value.The severity of CMT was positively correlated with the root-mean-square values of sternocleidomastoid muscle,platysma muscle,and upper trapezius muscle(r was 0.721,0.612,0.655,P<0.001).Conclusion sEMG could be used as a good method for the clinical diagnosis and evaluation of congenital muscular torticollis in children.

Objective To investigate the dynamic changes of left ventricular longitudinal systolic function in patients with atrial septal defect(ASD)and pulmonary hypertension(PH)before and after interventional occlusion using echocardiography.Methods A total of 57 patients undergoing interventional occlusion in Zhongshan Hospital,Fudan University from September 2015 to January 2016 were enrolled.Patients were divided into PH group and non-PH group.Echocardiographic examinations were performed for all subjects one day before,one day after and 1-6 months after the interventional occlusion.Twenty healthy individuals were included as a control group.Global and regional longitudinal strain(LS)of the left ventricle were analyzed using TomTec software.Results There were 27 patients in the PH group and 30 patients in the non-PH group.At baseline,tricuspid annular plane systolic excursion(TAPSE)and tissue Doppler velocity of tricuspid annulus S'in both the PH and non-PH groups were higher than those in the control group(P＜0.05).Longitudinal systolic function of the right ventricle decreased significantly on the first day after occlusion(P＜0.05),and slightly increased 1-6 months after occlusion.Patients in the non-PH group showed a decreased LS in a small portion of the left ventricular segments 1 d and 1-6 months after occlusion(P＜0.05);patients in the PH group showed a decreased left ventricular global longitudinal strain(GLS)on the first day after occlusion(P＜0.05),primarily was in the basal and middle parts of the ventricle(P＜0.05),without significant change in the apical part,and the LS of the left ventricle tended to increase 1-6 months after occlusion.Conclusions With or without PH,longitudinal movement of the right ventricle in ASD patient is excessive before occlusion,and gradually improves after occlusion.Left ventricular GLS decreases in ASD patients with PH,with segmental differences 1 day after occlusion.