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2.
J Basic Microbiol ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955034

RESUMO

Prodigiosin is a natural red pigment derived primarily from secondary metabolites of microorganisms, especially Serratia marcescens. It can also be chemically synthesized. Prodigiosin has been proven to have antitumor, antibacterial, antimalaria, anti-insect, antialgae, and immunosuppressive activities, and is gaining increasing important in the global market because of its great potential application value in clinical medicine development, environmental treatment, preparation of food additives, and so on. Due to the low efficiency of prodigiosin chemical synthesis, high-level prodigiosin of production by microorganisms are necessary for prodigiosin applications. In this paper, the production of prodigiosin by microorganism in recent decades is reviewed. The methods and strategies for increasing the yield of prodigiosin are discussed from the aspects of medium composition, additives, factors affecting production conditions, strain modification, and fermentation methods.

3.
Water Res ; 198: 117137, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33957311

RESUMO

Transition metal catalyzed sulfite auto-oxidation is a promising technology used in water and wastewater treatment for the elimination of contaminants. In the literature, this process has been reported to be efficient only in the presence of oxygen. However, in this study, we unexpectedly found that the degradation of diatrizoate (DTZ) by a system based on the combination of copper ion and sulfite (Cu(II)/S(IV)) reached over 95% under anaerobic conditions, but was considerably retarded under aerobic conditions at pH 7. Furthermore, it was found that Cu(I), generated from the cleavage of the CuSO3 complex, was the main reactive species responsible for the degradation of DTZ by the Cu(II)/S(IV) system under anaerobic conditions. In fact, the absence of oxygen promoted the accumulation of Cu(I). The concomitant release of the iodide ion with the degradation of DTZ indicated that the anaerobic degradation of DTZ by the Cu(II)/S(IV) system mainly proceeded through the deiodination pathway, which was also confirmed by the detection of deiodinated products. The anaerobic degradation of DTZ was favored at higher initial concentrations of Cu(II) or sulfite in this system. Since the CuSO3 complex, the precursor of Cu(I), was formed mainly at pH 7, the highest anaerobic degradation of DTZ was achieved at pH 7. An increase in reaction temperature considerably enhanced the degradation of DTZ by the Cu(II)/S(IV) system with an apparent activation energy of 119.4 kJ/mol. The presence of chloride, bicarbonate and humic acid slightly influenced the anaerobic degradation of DTZ. The experiments with real water samples also demonstrated the effectiveness of the degradation of DTZ by the Cu(II)/S(IV) system under anaerobic conditions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33864679

RESUMO

OBJECTIVE: To determine the outcomes in women with pulmonary hypertension (PH) and determine the factors related to adverse outcomes. METHODS: Data from 684 women with PH admitted to the Affiliated Renji Hospital from January 2001 to December 2020 were collected. Outcomes were compared based on the causes and severity of PH. RESULTS: The overall mortality was 2.8%, decreasing from 6.6% in 2001-2005 to 1.7% in 2016-2020 (P = 0.10). Idiopathic PH had the highest mortality (35.3%) and the lowest live birth rate (82.4%). Mortality was similar between moderate and severe PH (5.3% versus 9.7%), but the live birth rate was much lower in severe PH (78.6% versus 89.9%). Hypoxemia and vaginal birth were risk factors of maternal death (odds ratio [OR] 35.28, 95% confidence interval [CI] 1.42-878.75; OR 850.86, 95% CI 5.67-127 606.74, respectively). General anesthesia was a risk factor in the univariate analysis (OR 12.07, 95% CI 3.72-39.15) but was not significant in the multivariate analysis (P = 0.16). CONCLUSION: The mortality rate in this retrospective study was lower than that previously reported. Pregnancy is safe in mild PH but still has a high risk of complications in moderate and severe PH. Hypoxemia is a risk factor for maternal death, but cesarean section may be a protective factor.

6.
Int J Mol Sci ; 22(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922657

RESUMO

BRCA mutation, one of the most common types of mutations in breast and ovarian cancer, has been suggested to be synthetically lethal with depletion of RAD52. Pharmacologically inhibiting RAD52 specifically eradicates BRCA-deficient cancer cells. In this study, we demonstrated that curcumin, a plant polyphenol, sensitizes BRCA2-deficient cells to CPT-11 by impairing RAD52 recombinase in MCF7 cells. More specifically, in MCF7-siBRCA2 cells, curcumin reduced homologous recombination, resulting in tumor growth suppression. Furthermore, a BRCA2-deficient cell line, Capan1, became resistant to CPT-11 when BRCA2 was reintroduced. In vivo, xenograft model studies showed that curcumin combined with CPT-11 reduced the growth of BRCA2-knockout MCF7 tumors but not MCF7 tumors. In conclusion, our data indicate that curcumin, which has RAD52 inhibitor activity, is a promising candidate for sensitizing BRCA2-deficient cells to DNA damage-based cancer therapies.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33926183

RESUMO

A stretchable conductor is one of the key components in soft electronics that allows the seamless integration of electronic devices and sensors on elastic substrates. Its unique advantages of mechanical flexibility and stretchability have enabled a variety of wearable bioelectronic devices that can conformably adapt to curved skin surfaces for long-term health monitoring applications. Here, we report a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)-based stretchable polymer blend that can be patterned using an inkjet printing process while exhibiting low sheet resistance and accommodating large mechanical deformations. We have systematically studied the effect of various types of polar solvent additives that can help induce phase separation of PEDOT and PSS grains and change the conformation of a PEDOT chain, thereby improving the electrical property of the film by facilitating charge hopping along the percolating PEDOT network. The optimal ink formulation is achieved by adding 5 wt % ethylene glycol into a pristine PEDOT:PSS aqueous solution, which results in a sheet resistance of as low as 58 Ω/□. Elasticity can also be achieved by blending the above solution with the soft polymer poly(ethylene oxide) (PEO). Thin films of PEDOT:PSS/PEO polymer blends patterned by inkjet printing exhibits a low sheet resistance of 84 Ω/□ and can resist up to 50% tensile strain with minimal changes in electrical performance. With its good conductivity and elasticity, we have further demonstrated the use of the polymer blend as stretchable interconnects and stretchable dry electrodes on a thin polydimethylsiloxane (PDMS) substrate for photoplethysmography (PPG) and electrocardiography (ECG) recording applications. This work shows the potential of using a printed stretchable conducting polymer in low-cost wearable sensor patches for smart health applications.

9.
Mol Cell Probes ; 57: 101730, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33848593

RESUMO

Getah virus (GETV), a mosquito-borne virus belonging to the Alphavirus genus of family Togaviridae, has become increasingly problematic, which poses a huge threat to the safety of animals and public health. In order to detect GETV quickly and accurately, we have developed a SYBR Green I real-time quantitative reverse transcription PCR (RT-qPCR) assay for GETV with the detection limit of 66 copies/µL, excellent correlation coefficient (R2) of 0.9975, and amplification efficiency (E) of 98.90%, the target selected was the non-structural protein 3 of GETV. The sensitivity of it was higher than that of ordinary RT-PCR by 1000 folds, and the inter-assay and intra-assay CV values were all less than 0.99%. The newly developed RT-qPCR assay exhibited good sensitivity and reproducibility, which will provide technical support for the reliable and specific rapid diagnosis, and quantitative analysis of GETV infection.

10.
Ren Fail ; 43(1): 709-717, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33896382

RESUMO

BACKGROUND: The relationship between sleeping disorders and chronic kidney disease (CKD) has already been reported. Snoring, a common clinical manifestation of obstructive sleep apnea-hypopnea syndrome, is of clinical value in assessing sleeping disorder severity. However, investigations of the connection between snoring and CKD are limited, especially in normal-weight populations. This study assessed the relationship between snoring frequency and CKD in obese and normal-weight people in China. METHODS: A community-based retrospective cross-sectional study of 3250 participants was performed. Study participants were divided into three groups - the regularly snoring group, occasionally snoring group, and never snoring group - based on their self-reported snoring frequency. CKD was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2. Multiple logistic regression analysis was used to explore the relevance between snoring frequency and CKD prevalence. RESULTS: The CKD prevalence in obese participants was higher than that in normal-weight participants. Frequent snorers had a higher prevalence of CKD than those who were not frequent snorers in the obese group. Snoring frequency was correlated with CKD prevalence in obese participants independent of age, sex, smoking and drinking status, systolic blood pressure, triglyceride level, high-density lipoprotein, and homeostasis model assessment of insulin resistance (odds ratio: 2.66; 95% CI: 1.36-5.19; p=.004), while the same relationships did not exist in normal-weight participants (odds ratio: 0.79; 95% CI: 0.32-1.98; p=.614). CONCLUSIONS: Snoring appears to be independently associated with CKD in obese but not in normal-weight Chinese adults.

11.
Medicine (Baltimore) ; 100(17): e25685, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907141

RESUMO

BACKGROUND: Despite the developments in diagnosis and treatment of HER2-positive metastatic breast cancer, there is a high likelihood in the development of resistance to trastuzumab. In general, HER2-positive patients with deteriorated health face negative clinical outcomes. The present study is conducted to systematically explore the medicinal properties of trastuzumab in HER2-positive breast cancer patients. METHODS: Randomized controlled trials investigating the clinical properties of including trastuzumab to treat HER2-positive breast cancer cases will be sourced by exploring these online-based databases: MEDLINE, BIOSIS, China National Knowledge Infrastructure (CNKI), Cochrane Library, EMBASE, Central Register of Controlled Trials, and WanFang. Two independent authors will screen the literature, gather data, and assess the quality of selected studies. The significance of the relationship between the medical properties of trastuzumab when incorporated to treat HER2-positive breast cancer cases will be evaluated according to the relative risk, mean differences or standardized mean differences, and 95% confidence interval. RESULTS: The outcomes from this review shall be issued in a journal that will be reviewed by peers. CONCLUSION: The conclusions presented in this review will serve as a reference for clinical practitioners and scholars to determine whether trastuzumab is an effective and safety intervention for treating HER2-positive breast cancer patients. ETHICS AND DISSEMINATION: Since this study is a systematic review of published studies, an ethical approval is not needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: March 31, 2021.osf.io/wvqkf (https://osf.io/wvqkf/).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/efeitos dos fármacos , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
12.
Neuroimage Clin ; 30: 102671, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33892431

RESUMO

Previous neuroimaging research of eating disorders such as anorexia nervosa and bulimia nervosa has mainly focused on clinical patients, indicating the crucial role of intrinsic connectivity networks involved in aberrant behavioral control (i.e., executive control network), reward reactivity (i.e., basal ganglia network), and excessive self-focused and body-focused ruminations (i.e., default mode network) in the onset and maintenance of eating disturbances. However, examinations of large-scale resting-state networks that support the role of cognitive control, reward sensitivity, and self-directed thinking in disordered eating have rarely involved non-clinical samples from the general population. This study, involving a total of 693 healthy young adults (68.69% females; mean age, 18.37 years), investigated these issues by using pre-defined functional regions of interest from the executive control network, basal ganglia network, default mode network, and a seed-based region of interest-to-region of interest approach. After statistically controlling for differences in age, sex, body mass index, and head motion, we observed significant associations of higher levels of eating disorder symptoms, especially bulimia-type eating (i.e., binge eating and a combination of binge eating and compensatory behaviors, such as purging via self-induced vomiting or laxative use, and compulsive exercise), with weaker intra-network and inter-network functional synchrony. These results remained significant after excluding underweight, overweight, and obese participants. These findings suggest that these neural circuits may play a key role in the symptoms of disordered eating in healthy adults. They further reveal that the less efficient information exchange within and between intrinsic networks associated with self-referential thinking, inhibitory control, and reward sensitivity are strongly related to eating disorder symptoms.

13.
Int J Legal Med ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33818632

RESUMO

The Hazara population across Durand line has experienced extensive interaction with Central Asian and East Asian populations. Hazara individuals have typical Mongolian facial appearances and they called themselves descendants of Genghis Khan's army. The people who speak the Balochi language are called Baloch. Previously, a worldwide analysis of Y-chromosomal haplotype diversity for rapidly mutating (RM) Y-STRs and with PowerPlex Y23 System (Promega Corporation Madison, USA) kit was created with collaborative efforts, but Baloch and Hazara population from Pakistan and Hazara population from Afghanistan were missing. In the current study, Yfiler Plus PCR Amplification Kit loci were examined in 260 unrelated Hazara individuals from Afghanistan, 153 Hazara individuals, and 111 Balochi individuals from Baluchistan Pakistan. For the Hazara population from Afghanistan and Pakistan overall, 380 different haplotypes were observed on these 27 Y-STR loci, gene diversities ranged from 0.51288 (DYS389I) to 0.9257 (DYF387S1), and haplotype diversity was 0.9992. For the Baloch population, every individual was unique at 27 Y-STR loci; gene diversity ranged from 0.5718 (DYS460) to 0.9371(DYF387S1). Twelve haplotypes were shared between 178 individuals, while only two haplotypes among these twelve were shared between 87 individuals in Hazara populations. Rst and Fst pairwise genetic distance analyses, multidimensional scaling plot, neighbor-joining tree, linear discriminatory analysis, and median-joining network were performed, which shed light on the history of Hazara and Baloch populations. The results of our study showed that the Yfiler Plus PCR Amplification Kit marker set provided substantially stronger discriminatory power in the Baloch population of Pakistan and the Hazara population across the Durand line.

14.
Thorac Cancer ; 12(10): 1579-1588, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33793074

RESUMO

BACKGROUND: Esophageal cancer is one of the most common cancers across the globe; the 5-year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development. METHODS: Through experiments in vivo and in vitro, we explored potential signaling pathways, miR-493/Wnt5A/c-JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens. RESULTS: Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR-493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR-493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR-493 inhibits the activity of c-JUN and p-PI3K/p-AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c-JUN binds the promoter region of miR-493 and suppressed the expression of miR-493, forming a negative feedback loop. CONCLUSIONS: The miR-493/Wnt5A/c-JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.

15.
BMC Plant Biol ; 21(1): 177, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849439

RESUMO

BACKGROUND: Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. RESULTS: In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5-15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10-60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25-50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. CONCLUSIONS: These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

16.
Dermatol Ther ; : e14956, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33843123

RESUMO

Acne vulgaris is a common condition. Alpha hydroxy acid (AHA) peels have been previously recommended as an option for patients with intolerance to first-line treatments especially when long-term use. The safety and efficacy of AHA peels for acne have been established, but the factors influencing the ultimate effects are unknown. We recruited patients diagnosed with acne who were intolerant to or refused the first-line treatments from July 2017 to December 2019 at our hospital and retrospectively collected the medical and demographic information of patients treated with a full course of AHA peels; data collected included age, sex, treatment history, compliance status, and efficacy after treatment. The efficacy score was defined by revised scales: 2 points indicated significant improvement, 1 point indicated mild improvement, and 0 point indicated no improvement. Additionally, only efficacy scores of 2 points were classified in the satisfactory group; the others were classified in the unmet effect group. Analyses were used to evaluate the potential influencing factor(s). A total of 141 patients (120 females, 21 male) were included in the final analysis. The patients in the satisfactory group were significantly older (higher proportion aged >28 years) (47.4% vs 29.5%, P = .046) and showed better compliance (88.7% vs 54.5%, P = .001) than the patients in the unmet effect group. Multiple analyses confirmed the effects of younger age (OR 2.70, 95% CI 1.15-6.34, P = 022) and poor compliance (OR 2.74, 95% CI 1.74-4.32, P = .001) on the unmet effect. Unsatisfactory compliance and age might decrease the effects of AHA peels on acne.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33837779

RESUMO

CONTEXT: Intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) prediction are pivotal topic of interests in Kawasaki disease (KD). However, data on the predictive value of lipid profile for both IVIG resistance and CALs are limited. PURPOSE: To investigate the predictive validity of lipid profile for IVIG resistance and CALs in KD. DESIGN: Prospective cohort study. SETTING: West China Second University Hospital. PATIENTS: 363 KD patients were divided into the initial IVIG-resistant group and initial IVIG-responsive group; repeated IVIG-resistant group and repeated IVIG-responsive group; CAL+ group and CAL- group. MAIN OUTCOME MEASURES: Validity of lipid profile in predicting IVIG resistance and CALs. RESULTS: TG was significantly higher whereas TC, HDL-C, LDL-C as well as Apo A were significantly lower in initial IVIG-resistant subjects, with cut-off values of 1.625 mmol/L, 3.255 mmol/L, 0.475 mmol/L, and 1.965 mmol/L and 0.665 g/L, yielding sensitivities of 52%, 70%, 52%, 61%, 50%, and specificities of 68%, 53%, 78%, 71%, 81%, respectively. TC, LDL-C, and Apo A levels were significantly lower in repeated IVIG-resistant subjects, with cut-off values of 3.20 mmol/L, 1.78 mmol/L, 0.605 g/L, producing sensitivities of 91%, 70%, 57% and specificities of 55%, 67%, 70%, respectively. Apo-A level was significantly lower in the CAL group, with cut-off value of 0.805g/L, yielding sensitivity of 66% and specificity of 54%. CONCLUSIONS: Lipid profiles were significantly dysregulated in KD patients suffering IVIG resistance and CALs. Some of them, such as LDL-c and Apo-A, could serve as complementary laboratory markers for predicting both IVIG resistance and CALs.

18.
BMC Surg ; 21(1): 112, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33663419

RESUMO

BACKGROUND: Neuroblastoma is the most common malignant extracranial solid tumor in pediatrics patients. Intraoperative hyperthermia is extremely rare in patients with neuroblastoma and can cause a series of complications. Here, we represent a case of neuroblastoma accompanied by hyperthermia during anesthesia, and propose a rational explanation and management options. CASE PRESENTATION: The patient had gait disturbance and sitting-related pain without fever. Magnetic resonance imaging revealed a soft tissue mass located in the right posterior mediastinum, paravertebral space and canalis vertebralis. Serum tumor marker screening showed that the patient had increased epinephrine, norepinephrine and neuron specific enolase levels, with an increased 24 hour urine vanillylmandelic acid level. Intraspinal tumor resection was conducted. The temperature of the patient rapidly arose to 40.1 °C over 10 minutes when waiting for tracheal extubation. The arterial gas analysis results indicated malignant hyperthermia was less likely, and dantrolene was not administered. Physical cooling methods were used, and the temperature dropped to 38.6 â„ƒ. The trachea was successfully extubated. Histological results confirmed the diagnosis of neuroblastoma. CONCLUSIONS: Hyperthermia during anesthesia is a serious adverse event. Catecholamines secreted from neuroblatoma cells can lead to hypermetabolism and hyperthermia. Surgeons and anesthesiologists should be aware of the possibility of hyperthermia in patients with neuroblastoma.


Assuntos
Hipertermia Maligna , Neuroblastoma , Criança , Humanos , Neuroblastoma/diagnóstico
19.
Ann Thorac Surg ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33689738

RESUMO

To deal with calcified ascending aorta during CABG, we describe an alternative technique to create a clampless proximal anastomosis using a Foley catheter and polypropylene suture. In 30 patients, the number of distal anastomoses averaged 3.1 ± 0.7, and mean time of proximal anastomosis was 18.9 ± 1.3 minutes, respectively. Neither early nor late death occurred. Stroke occurred in 2 high-risk patients. At mean 1.6 ± 0.5 years of follow-up, 1 patient sustained recurrent angina, and graft patency was 93%. These favorable outcomes show that this alternative technique is a safe and effective approach to calcified ascending aorta in CABG.

20.
Eur J Drug Metab Pharmacokinet ; 46(3): 353-371, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677821

RESUMO

BACKGROUND AND OBJECTIVE: Prior olanzapine population pharmacokinetic (PPK) models have focused on the effects of sex and smoking on olanzapine clearance. This PPK model in Chinese adult psychiatric patients also investigated the influence of comedications and co-occurrence of infections on olanzapine clearance, and explored how to personalize oral olanzapine dosage in the clinical setting. METHODS: A total of 1546 serum concentrations from 354 patients were collected in this study. A one-compartment model with first-order absorption was employed to develop the PPK model using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, co-occurrence of infection and concomitant medications (including dangguilonghui tablets, a Chinese herbal medicine for constipation). Bootstrap validation (1000 runs) and external validation of 50 patients were employed to evaluate the final model. Simulations were performed to explore the personalization of olanzapine dosing after stratification by sex, smoking, and comedication with valproate. RESULTS: Typical estimates for the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) were 0.30 h-1, 12.88 L/h, and 754.41 L, respectively. Olanzapine clearance was increased by the following variables: 1.23-fold by male sex, 1.23-fold by smoking, 1.23-fold by comedication with valproate, 1.16-fold by sertraline, and 2.01-fold by dangguilonghui tablets. Olanzapine clearance was decreased by the following variables: 0.75-fold by co-occurrence of infection, 0.70-fold by fluvoxamine, and 0.78-fold by perphenazine. The model evaluation indicated that the final model's performance was good, stable, and precise. CONCLUSION: This study contributes to the personalization of oral olanzapine dosing, but further studies should be performed to verify the effects of infection and comedications, including valproate and dangguilonghui.

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