The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.
Anticoagulants ; pharmacology ; Body Weight ; Cytochrome P-450 CYP2C9 ; genetics ; Genotype ; Humans ; International Normalized Ratio ; Nonlinear Dynamics ; Polymorphism, Genetic ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; pharmacokinetics

OBJECTIVE: An automatic detection tool was created for examining health-related webpage quality we went further by examining its feasibility and performance. METHODS: We developed an automatic detection system to auto-assess the authorship quality indicator of an health-related information webpage for governmental websites in Taiwan. The system was integrated with the Chinese word segmentation system developed by the Academia Sinica in Taiwan and the SVM(light), which serve as an SVM (Support Vector Machine) Classifiers and a method of information extraction and identification. The system was coded in Visual Basic 6.0, using SQL 2000. RESULTS: We developed the first Chinese automatic webpage classification and information identifier to evaluate the quality of web information. The sensitivity and specificity of the classifier on the training set of webpages were both as high as 100% and only one health webpage in the test set was misclassified, due to the fact that it contained both health and non-health information content. The sensitivity of our authorship identifier is 75.3%, with a specificity of 87.9%. CONCLUSION: The technical feasibility of auto-assessment for the quality of health information on the web is acceptable. Although it is not sufficient to assure the total quality of web contents, it is good enough to be used to support the entire quality assurance program.
Asian Continental Ancestry Group ; Authorship ; Humans ; Quality Indicators, Health Care ; Sensitivity and Specificity ; Taiwan

Objective: To observe the inhibitory effects of biotic royal jelly on the ascitic hepatoma cell H22. Methods: Mice bearing H22 tumor were fed on different types of royal jelly: No.1, 2 and 3. Their anti-tumor effects were observed in vivo. The general royal jelly and normal saline were observed as control. Results: Among these biotic royal jelly, the biotic royal jelly No.1 showed obvious tumor-inhibiting and survival-prolonging effects. In addition, it increased the number of WBC and augmented the amount of IL-2 and IFN-γ; the pathological study also indicated the denaturing and necrosis of most tumor cells with nuclei constraining and cell membrane rupturing, and large amount of lymphocytes and plasmacytes infiltrating around the mass. Conclusion: The No.1 biotic royal jelly has obvious anti-tumor effect, and it may take effects by inhibiting or killing tumor cells and improving the immunity of the host.

The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.
Adult ; Aged ; Analgesics ; blood ; pharmacokinetics ; Body Weight ; Female ; Flurbiprofen ; administration & dosage ; analogs & derivatives ; blood ; metabolism ; pharmacokinetics ; therapeutic use ; Head and Neck Neoplasms ; surgery ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Models, Biological ; Pain, Postoperative ; drug therapy ; prevention & control ; Prospective Studies ; Software ; Young Adult

Background: and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. Methods: All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. Results: No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. Conclusions Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

Background and Objectives: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. Methods: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. Results: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14–1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. Conclusions Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

OBJECTIVETo further understand the clinical features of non-gastric mucosa-associated lymphoid tissue (MALT) lymphoma and investigate its suitable treatment.

METHODSA retrospective survey of 57 non-gastric MATL lymphoma patients pathologically confirmed in our hospital from 1999 to 2011.

RESULTSThe median age was 58 years (range 14-86 years). Common presenting sites of non-gastric MALT lymphoma included lungs and upper respiratory tract (17 patients, 29.8%), intestinal tracts (16 patients,28.1%), orbital and ocular adnexal (7 patients, 12.3%), and salivary glands (8 patients, 14.0%). Stage Ⅰ-Ⅱdisease presented in 35 patients (61.4%), stage Ⅲ-Ⅳ disease in 22 patients (38.6%). A total of 26 patients had nodal involvement and 7 patients multiple organ involvement. Regimens included surgery alone, chemotherapy alone, surgery followed by chemotherapy or chemoradiotherapy. The complete response (CR) rate was 66.0% and the overall response rate 85.7%. At a median follow-up of 52 months, the 5-year overall survival (OS) and the 5-year progression free survival (PFS) were 91.6% and 77.7%, respectively. The 5-year survival rate of surgery, chemotherapy, surgery+chemotherapy, surgery + chemotherapy + radiotherapy groups were 87.5%, 100.0%, 90.2% and 100.0%, respectively, without significant differences. The 5-year PFS of the four groups were 62.3%, 80.0%, 90.2% and 75.0% respectively.

CONCLUSIONNon-gastric MALT lymphoma is characterized by disseminated onset, favorable response to treatments and good outcomes. There is no statistically significant difference in the overall survival of the various treatments. But the recurrence rate of surgery alone is relatively high (22.3%).

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell, Marginal Zone ; diagnosis ; pathology ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the distribution of sentinel lymph nodes in gastric cancer, and evaluate clinicopathologic characteristics leading its metastasis.

METHODSThe location of metastatic lymph nodes was analyzed retrospectively in 27 patients of gastric carcinoma with solitary lymph node metastases, and in 80 cases metastasis was limited to only 1 station in Japanese nodal classification. The clinicopathologic characteristics of the patients with solitary lymph node metastases and 111 cases without lymph node metastases were compared.

RESULTSTwenty-five in 27 cases with solitary lymph node metastases were limited in level I. Skip metastasis occurred in 2 cases. Sentinel lymph nodes of 16 cases in 21 patients with the tumors in the lower and middle third stomach were located in less curvature (No. 3) and in greater curvature (No. 4). Sentinel lymph nodes of 3 cases in 6 patients in the upper third stomach were located in right cardia (No. 1). Multivariate analysis showed that the frequency of sentinel lymph node metastasis of pT(3) lesion was significantly higher than that of pT(1) lesion with an odds ratio of 4.926 (P < 0.01). The frequency of sentinel lymph node metastasis in the tumor located in the upper third stomach was significantly higher than that in lower third stomach, with an odds ratio of 4.381 (P < 0.05). Early gastric cancer had lower risk for sentinel lymph node metastasis than that in Borrmann type I cancer, with an odds ratio of 0.082 (P < 0.05).

CONCLUSIONSMajority of sentinel lymph nodes are located in the regional perigastric lymph node groups close to the tumor. Skip metastasis is rare. Depth of invasion and location of tumor are correlated with sentinel lymph node metastasis. Sentinel lymph node assessment can instruct to determine extent of lymph node dissection for gastric cancer.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Stomach Neoplasms ; pathology ; surgery

Objective To investigate the brain areas having functional connectivity with nucleus accumbens in heroin addicts with resting-state functional magnetic resonance imaging (fMRI), and explore the reward system of heroin addiction. Methods Fifteen participants with heroin addiction,voluntarily admitted to our drug rehabilitation center from June 2009 to March 2010, and 15 healthy controls at the same period were chosen in our study. Resting-state fMRI was performed on these patients; and then, the resting-state brain functional connectivity was also concluded by analyzing the left and right nucleus accumbens selected as regions of interests (ROIs). The corresponding brain areas having functional connections with ROIs were defined in the resting-state and the changes of functional connectivity were observed in heroin addicts. Results In the addiction group, the areas having functional connectivity with double nucleus accumbens included bilateral thalamus, the basal ganglia, the hippocampus, the midbrain and contralateral nucleus accumbens; and anterior cingulate cortex was also significantly correlated with left nucleus accumbens. However, in the control group, only the hippocampus and contralateral nucleus accumbens had these connection and their activity was much weaker than that in the addiction group. Conclusion In the resting-state, reward system of heroin addiction is constituted by the brain areas having functional connectivity with nucleus accumbens. And fMRI can be used to study the functional connections between the brain areas related to the heroin addiction from neuroimaging perspectives.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.