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1.
Water Res ; 264: 122222, 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39128202

ABSTRACT

Industrial wastewater contained a large amount of refractory organics, and single treatment processes had limitations. This study investigated the mechanism of refractory organics removal using iron-carbon built-in coupled activated sludge (ICAS) and explored the role and function of iron-carbon (IC) within the ICAS system. The aerobic granular sludge (AGS) cultivated with IC exhibited a loose surface and a tight interior structure. Iron in the AGS concentrated near the outer layer to form a crust, which protected the inner microorganisms. IC promoted EPS secretion and regulated the abundance of positive and negative signaling molecules to maintain AGS stability. Experiments using quinoline as a model refractory organic showed that both physical adsorption by IC and biological adsorption by sludge rapidly fixed a large amount of pollutants, providing a buffer capacity for the system. The iron mineral crust on the AGS surface enhanced quinoline adsorption. Hydroxylation was the first step in quinoline degradation, with IC upregulating the genes iorA/B, qorB, and wrbA involved in this process, and the relative abundances of quinoline-degrading bacteria. Both pyridine ring opening and benzene ring cleavage occurred in the single IC system, and the microelectrolysis process produced •OH and [H], which made degradation pathway for quinoline through IC more complex than microbial degradation. Although the IC-mediated pathway accounted for only a small part of overall quinoline removal in the ICAS system, the ICAS system not only preserved the microelectrolysis process but also enhanced microbial metabolic activity. This work provided insights into the synergistic removal of pollutants and maintenance of AGS stability by the ICAS process, ensuring efficient treatment of refractory organic wastewater.

2.
Ther Drug Monit ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39115815

ABSTRACT

BACKGROUND: Ripretinib, a recently developed tyrosine kinase inhibitor with switch-control abilities, can inhibit both primary and secondary activation of KIT(KIT proto-oncogene receptor tyrosine kinase) and platelet-derived growth factor receptor alpha (PDGFRA) mutants, which contribute to gastrointestinal stromal tumor progression. METHODS: In this study, a high-performance liquid chromatography-tandem mass spectrometry method to measure the concentrations of ripretinib and its active desmethyl metabolite DP-5439 in human plasma was developed and validated. Plasma samples were extracted and recovered by precipitation with acetonitrile containing the internal standard and diluted with acetonitrile before analysis. Ripretinib and DP-5439 were separated using chromatography on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 µm) with gradient elution using 0.1% formic acid and 5 mM ammonium formate in water as mobile phase A and acetonitrile as mobile phase B. The mobile phase was set to a flow rate of 0.5 mL/min. RESULTS: The calibration curves were linear across the following concentration range: 7.5 to 3000 ng/mL for ripretinib and 10 to 4000 ng/mL for DP-5439. The intraday and interday precisions were approximately 15% for all analytes in the quality control samples. The relative matrix effects in extracted plasma samples (90.3%-108.8% at different levels) were considered acceptable. CONCLUSIONS: This method will be a useful tool in oncology to facilitate the further clinical development of ripretinib.

3.
J Clin Neurophysiol ; 41(5): 415-422, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38935655

ABSTRACT

PURPOSE: Stereotactic EEG (SEEG) is gaining increasing popularity in the United States. Patients undergoing SEEG have unique challenges, and their needs are different compared with noninvasive cases. We aim to describe the medical, nursing, and other institutional practices of SEEG evaluations among tertiary referral (level IV) epilepsy centers accredited by the National Association of Epilepsy Centers. METHODS: We analyzed data obtained from a Research Electronic Data Capture (REDCap) survey we formulated and distributed to directors of all level IV epilepsy centers listed by the National Association of Epilepsy Center. Most questions were addressed to the adult and pediatric SEEG programs separately. RESULTS: Among 199 epilepsy center directors invited to complete the survey, 90 (45%) responded. Eighty-three centers (92%) reported they perform SEEG evaluations. Of the 83 respondents, 56 perform SEEG in adult and 47 in pediatric patients. Twenty-two centers evaluate both pediatric and adult subjects. The highest concordance of SEEG workflow was in (1) epilepsy monitoring unit stay duration (1-2 weeks, 79% adult and 85% pediatric programs), (2) use of sleep deprivation (94% both adult and pediatric) and photic stimulation (79% adult and 70% pediatric) for seizure activation, (3) performing electrical cortical stimulation at the end of SEEG evaluation after spontaneous seizures are captured (84% adult and 88% pediatric), and (4) daily head-wrap inspection (76% adult and 80% pediatric). Significant intercenter variabilities were noted in the other aspects of SEEG workflow. CONCLUSIONS: Results showed significant variability in SEEG workflow across polled centers. Prospective, multicenter protocols will help the future development and harmonization of optimal practice patterns.


Subject(s)
Electroencephalography , Epilepsy , Stereotaxic Techniques , Humans , Epilepsy/surgery , Epilepsy/physiopathology , Epilepsy/diagnosis , Epilepsy/therapy , Adult , Child , Male
5.
Physiol Plant ; 176(2): e14246, 2024.
Article in English | MEDLINE | ID: mdl-38467573

ABSTRACT

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) within plant cells due to unfavourable conditions leads to ER stress. This activates interconnected pathways involving reactive oxygen species (ROS) and unfolded protein response (UPR), which play vital roles in regulating ER stress. The aim of this study is to investigate the underlying mechanisms of tunicamycin (TM) induced ER stress and explore the potential therapeutic applications of tauroursodeoxycholic acid (TUDCA) in mitigating cellular responses to ER stress in Pak choi (Brassica campestris subsp. chinensis). The study revealed that ER stress in Pak choi leads to detrimental effects on plant morphology, ROS levels, cellular membrane integrity, and the antioxidant defence system. However, treatment with TUDCA in TM-induced ER stressed Pak choi improved morphological indices, pigment contents, ROS accumulation, cellular membrane integrity, and antioxidant defence system restoration. Additionally, TUDCA also modulates the transcription levels of ER stress sensors genes, ER chaperone genes, and ER-associated degradation (ERAD) genes during ER stress in Pak choi. Furthermore, TUDCA has demonstrated its ability to alleviate ER stress, stabilize the UPR, reduce oxidative stress, prevent apoptosis, and positively influence plant growth and development. These results collectively comprehend TUDCA as a promising agent for mitigating ER stress-induced damage in Pak choi plants and provide valuable insights for further research and potential applications in crop protection and stress management.


Subject(s)
Antioxidants , Taurochenodeoxycholic Acid , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , Taurochenodeoxycholic Acid/pharmacology , Endoplasmic Reticulum Stress , Tunicamycin/pharmacology
6.
J Tradit Chin Med ; 44(1): 70-77, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38213241

ABSTRACT

OBJECTIVE: To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) molecule, which can prevent colorectal cancer (CRC) in the 1,2-Dimethylhydrazine (DMH)/dextran sodium sulphate (DSS)-induced mouse model. METHODS: Institute of cancer research (ICR) male mice were injected with 20 mg/kg DMH for a week. After that, 2% DSS was administered in the drinking water for another 7 d. The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice. Histopathological examination was used for observing the CRC development at colonic mucosa. Immunohistochemistry (IHC), blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC. The reversing targets searching method was applied with artificial intelligence (AI), computer-aided drug designing (CADD) and Ingenuity Pathway Analysis (IPA) techniques for predicting the potential targets and mechanism of CADPE highly related to CRC. RESULTS: The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment. CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development. Finally, our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) in two major cancer development pathways. CONCLUSIONS: CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR, ERK and mTOR activities in two highly related CRC developing pathways.


Subject(s)
Caffeic Acids , Colorectal Neoplasms , Dextrans , Sulfates , Mice , Male , Animals , 1,2-Dimethylhydrazine/pharmacology , Dextrans/pharmacology , Artificial Intelligence , Colorectal Neoplasms/chemically induced , Colorectal Neoplasms/drug therapy , Signal Transduction , Inflammation , ErbB Receptors/genetics , TOR Serine-Threonine Kinases/genetics , Mammals
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1023404

ABSTRACT

In the context of "New Era" and "New Medicine", the teaching team of laboratory diagnostics proposed a new teaching method of PDCA (Plan, Do, Check, Action) cycle to innovate the instructional design and implementation of laboratory diagnosis on the base of traditional teaching model. Through optimizing the curriculum system, integrating superior resources, taking full advantage of information technology, mobilizing the virtual simulation laboratory, implementing moral education and multiple comprehensive evaluation results, the self-learning enthusiasm, innovation and development ability of students were improved significantly, accompanied with high humanistic care spirit. Moreover, the enthusiasm of participating in scientific research activities and professional competitions was enhanced obviously. Therefore, we believe that the PDCA cycle, with notable successes, deserves high promotion value and wide application.

8.
Chinese Medical Ethics ; (6): 636-642, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012954

ABSTRACT

Vaccine cooperation is an important means to deal with global infectious diseases. However, the cooperation cannot be achieved overnight. Ethical dilemma is one of the obstacles that hinders vaccine cooperation. Reviewing the history, the most successful vaccine collaboration to date has been the global smallpox eradication program. In the process of eradicating smallpox, there were also many ethical dilemmas, including the international pattern of the US-Soviet hegemony, which impacted the mutual help between countries, the ethical disputes of the vaccine itself hindering solidarity and cooperation among actors, and the vaccine coercion adopted to overcome vaccine hesitancy undermining the principle of proportionality among the freedom, equality and efficacy. The ethical dilemmas of vaccine cooperation were resolved by shaping professional and scientific consensus among medical professional groups, reaching consensus on cooperation between leading countries and developing countries, and integrating local culture to improve vaccination methods. Finally, in 1980, the world successfully eradicated smallpox. The case of smallpox eradication provides us lessons for vaccine cooperation against COVID-19 and the construction of a community of common health for mankind today.

9.
Acta Pharmaceutica Sinica ; (12): 764-774, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016607

ABSTRACT

italic>Cynanchum wallichii and Cynanchum otophyllum belong to the genus Cynanchum in the family Apocynaceae, and are important medicinal plants. In this study, we sequenced and assembled the chloroplast genomes of C. wallichii and C. otophyllum, and performed a phylogenetic analysis of the structural characteristics of their chloroplast genomes and their phylogenetic positions. The results showed that the chloroplast genomes of both C. wallichii and C. otophyllum had a typical tetrad structure, with 133 genes annotated, and the total GC contents of both were similar. Codon preference analysis showed that the relative synonymous codon usage in the chloroplast genomes of C. wallichii and C. otophyllum differed slightly, but the differences were not significant, and there was a strong A or U preference at the third codon position. In both chloroplast genomes, 91 and 103 simple sequence repeats were detected respectively, and the largest proportion of A/T type repeats. Nucleotide polymorphism analysis showed that the nucleotide diversity of the intergenic sequences in the chloroplast genome of genus Cynanchum were generally higher than those of the common gene sequences. A pair of primers was designed based on the high variation region of the chloroplast genome to identify C. wallichii and C. otophyllum. The phylogenetic analysis showed that the C. wallichii and Cynanchum thesioides were the closest relatives, while the C. otophyllum, Cynanchum bungei and Cynanchum wilfordii formed a stable monophyletic clade within the genus Cynanchum, and the three species were closely related. The comparative analysis of the chloroplast genomic characteristics and phylogeny of C. wallichii and C. otophyllum will provide a theoretical basis for the species identification of the two plants and for the study of genetic diversity and phylogeny of the genus Cynanchum.

10.
Biomed Chromatogr ; 37(12): e5738, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37724003

ABSTRACT

We developed and validated sensitive MS/MS methods for the determination of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, in human plasma and cerebrospinal fluid (CSF). Acetonitrile was used as protein precipitant. The mobile phase was 10 mM ammonium formate consisting of 0.1% formic acid and acetonitrile (40:60, v/v). The analytes were separated on an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) in 5 min. An API 4000 mass spectrometer was selected to quantify venetoclax and internal standard using m/z 868.3 → 636.3 and 876.3 → 644.3 under multiple response monitoring mode. In plasma, the calibration curve exhibited good linearity ranging from 20.0 to 5000 ng/mL, whereas in the CSF, the linear range was 0.500-100 ng/mL. The matrix effect of venetoclax and internal standard (venetoclax-d8) was not obvious in both plasma and CSF. The inter- and intra-run accuracy was within ±11.9%, and the inter- and intra-run precision was below 13.6%. Both methods had no carryover, and the recovery was close to 100%. The validated methods were employed to quantify the concentrations of venetoclax in the plasma and CSF of patients diagnosed with chronic lymphocytic leukemia or acute myelogenous leukemia.


Subject(s)
Sulfonamides , Tandem Mass Spectrometry , Humans , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Reproducibility of Results , Acetonitriles , Chromatography, High Pressure Liquid/methods
11.
J Glob Antimicrob Resist ; 35: 347-353, 2023 12.
Article in English | MEDLINE | ID: mdl-37573945

ABSTRACT

OBJECTIVES: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. METHODS: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. RESULTS: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. CONCLUSION: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.


Subject(s)
Kidney Transplantation , Models, Biological , Humans , Adult , Linezolid/therapeutic use , Bayes Theorem , Computer Simulation , Kidney Transplantation/adverse effects
12.
BMC Genomics ; 24(1): 340, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37340366

ABSTRACT

BACKGROUND: Oriental river prawn (Macrobrachium nipponense) is one of the most dominant species in shrimp farming in China, which is a rich source of protein and contributes to a significant impact on the quality of human life. Thus, more complete and accurate annotation of gene models are important for the breeding research of oriental river prawn. RESULTS: A full-length transcriptome of oriental river prawn muscle was obtained using the PacBio Sequel platform. Then, 37.99 Gb of subreads were sequenced, including 584,498 circular consensus sequences, among which 512,216 were full length non-chimeric sequences. After Illumina-based correction of long PacBio reads, 6,599 error-corrected isoforms were identified. Transcriptome structural analysis revealed 2,263 and 2,555 alternative splicing (AS) events and alternative polyadenylation (APA) sites, respectively. In total, 620 novel genes (NGs), 197 putative transcription factors (TFs), and 291 novel long non-coding RNAs (lncRNAs) were identified. CONCLUSIONS: In summary, this study offers novel insights into the transcriptome complexity and diversity of this prawn species, and provides valuable information for understanding the genomic structure and improving the draft genome annotation of oriental river prawn.


Subject(s)
Palaemonidae , Animals , Humans , Palaemonidae/genetics , Gene Expression Profiling , Transcriptome , Alternative Splicing , Protein Isoforms/genetics
13.
Molecules ; 28(3)2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36770870

ABSTRACT

Ibrutinib, orelabrutinib, and zanubrutinib are all Bruton's tyrosine kinase inhibitors, which have greatly improved the treatment of B-cell malignancies. In this study, an LC-MS/MS method was developed and validated for the determination of orelabrutinib, zanubrutinib, ibrutinib, and its active metabolite dihydrodiol ibrutinib in human plasma. The Ibrutinib-d5 was used as the internal standard. Pretreatment was performed using a simple protein precipitation step using acetonitrile. The ACQUITY UPLC HSS T3 column (2.1×50 mm, 1.8 µm) was used to separate the analytes, and the run time was 6.5 min. The mobile phase consisted of acetonitrile and 10 mM of ammonium formate, which contained 0.1% formic acid. The multiple reactions' monitoring transitions were selected at m/z 428.1→411.2, 472.2→455.2, 441.1→304.2, 475.2→304.2 and 446.2→309.2 respectively for orelabrutinib, zanubrutinib, ibrutinib, dihydrodiol ibrutinib and ibrutinib-d5 using positive ion electrospray ionization. The standard curves were linear, from 0.400 to 200 ng/mL for ibrutinib and dihydrodiol ibrutinib, 1.00-500 ng/mL for orelabrutinib, and 2.00-1000 ng/mL for zanubrutinib. Selectivity, the lower limit of quantitation, precision, accuracy, matrix effect, recovery, stability, and dilution integrity all met the acceptance criteria of FDA guidance. This method was used to quantify the plasma levels of orelabrutinib, zanubrutinib, ibrutinib, and dihydrodiol ibrutinib in clinical patients.


Subject(s)
Protein Kinase Inhibitors , Tandem Mass Spectrometry , Humans , Chromatography, Liquid/methods , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Reproducibility of Results , Protein Kinase Inhibitors/pharmacology , Acetonitriles
14.
Epilepsy Behav Rep ; 21: 100582, 2023.
Article in English | MEDLINE | ID: mdl-36654732

ABSTRACT

Background: GNAO1-related neurodevelopmental disorder is a heterogeneous condition characterized by hypotonia, developmental delay, epilepsy, and movement disorder. This study aims to better understand the spectrum of epilepsy associated with GNAO1 variants and experience with anti-seizure medications, and to review published epilepsy phenotypes in GNAO1. Methods: An online survey was distributed to caregivers of individuals diagnosed with GNAO1 pathogenic variants, and a literature review was conducted. Results: Fifteen respondents completed the survey with the median age of 39 months, including a novel variant p.Q52P. Nine had epilepsy - six had onset in the first week of life, three in the first year of life - but two reported no ongoing seizures. Seizure types varied. Individuals were taking a median of 3 seizure medications without a single best treatment. Our cohort was compared to a literature review of epilepsy in GNAO1. In 86 cases, 38 discrete variants were described; epilepsy is reported in 53 % cases, and a developmental and epileptic encephalopathy in 36 %. Conclusions: While GNAO1-related epilepsy is most often early-onset and severe, seizures may not always be drug resistant or lifelong. Experience with anti-seizure medications is varied. Certain variant "hotspots" may correlate with epilepsy phenotype though genotype-phenotype correlation is poorly understood.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 288: 122191, 2023 Mar 05.
Article in English | MEDLINE | ID: mdl-36463623

ABSTRACT

In this work, a novel triphenylamine-benzofuran derived fluorescent probe, TBF-SS, was developed for detecting hydrogen polysulfide in tea samples and intracellular imaging. TBF-SS showed the practical advantages including high sensitivity (LOD = 0.01 µM), high selectivity, rapid response (within 15 min), and steadiness in various environmental conditions. The detecting system was steady within pH range of 6.0-11.0 and temperature range of 20-55 °C. The probe TBF-SS could guarantee the stable detection of H2Sn for 7 d in storage of either solid or solution. In particular, in the application of various tea samples with different brewing times and testing temperatures, the recovery percentages varied in the range of 95.22 % to 105.0 %. Therefore accurate monitoring of H2Sn could be achieved by using the probe TBF-SS. In addition, TBF-SS could monitor the exogenous level, the ß-lapachone-induced generation and the tea-sample-treated introduction of H2Sn in living MCF-7 cells. This work might inspire the improvement of the serviceability of fluorescent implements.


Subject(s)
Benzofurans , Fluorescent Dyes , Hydrogen/analysis , Tea
16.
Br J Clin Pharmacol ; 89(2): 526-535, 2023 02.
Article in English | MEDLINE | ID: mdl-35285970

ABSTRACT

AIMS: The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). METHODS: Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. RESULTS: The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004). CONCLUSION: Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.


Subject(s)
Acute Kidney Injury , Vancomycin , Humans , Vancomycin/adverse effects , Anti-Bacterial Agents/adverse effects , Pharmacists , Retrospective Studies , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Acute Kidney Injury/prevention & control , Creatinine
17.
Braz. J. Pharm. Sci. (Online) ; 59: e21343, 2023. tab, graf
Article in English | LILACS | ID: biblio-1439516

ABSTRACT

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.


Subject(s)
Tacrolimus/agonists , Impact Factor , Voriconazole/agonists , Cytochrome P-450 CYP2C19/analysis , In Vitro Techniques/methods , Pharmaceutical Preparations/administration & dosage , Adaptation, Psychological/classification
18.
Journal of Clinical Surgery ; (12): 1057-1060, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019258

ABSTRACT

Objective To investigate the correlation of fibulin 5(FBLN5)and Rho GTPase activating protein 4(ARHGAP4)in gastric cancer tissues and their relationship with the prognosis of patients.Methods One hundred gastric cancer patients admitted to the Department of General Surgery of Shijiazhuang First Hospital were selected for the study,and gastric cancer tissues>1 cm from the tumor margin and paracancerous tissues 5 cm from the tumor margin were collected.Retrospective analysis of the relationship between FBLN5 and ARHGAP4 expression profiles and clinicopathological indices of gastric cancer,as well as their effects on survival,was performed with univariate and Cox regression analyses of the patients'clinical data.Immunohistochemical staining was used to detect the expression of FBLN5 and ARHGAP4.The relationship between the expression levels of different FBLN5 and ARHGAP4 and the survival time of patients.Results The positive expression rate of ARHGAP4 was lower than that of paracancerent tissues,and the positive expression rate of FBLN5 was higher than that of paracancerent tissues(P<0.05).ARHGAP4 expression was associated with tumor site,Lauren's staging,lymph node metastasis,TNM stage,differentiation degree,CE,CA19-9,CA125,and immune score(P<0.05);FBLN5 expression was associated with Lauren's staging,lymph node metastasis,TNM stage,differentiation degree,CE,CA19-9,CA125,and immune score(P<0.05);Kaplan-Meier analysis showed that the 3-year cumulative survival rate of FBLN5 positive group was,which was lower than that of negative group(P=0.044).The 3-year cumulative survival rate of ARHGAP4 positive patients was higher than that of negative patients(P=0.021).Cox results showed that positive ARHGAP4 was protective factor for survival(P<0.05).Conclusion The prognosis of patients in the FBLN5-positive group is worse than that in the negative group,high expression of FBLN5 is a risk factor for survival,and the prognosis of patients with ARHGAP4 negative group is better than that in the positive group,which are closely related to the development and prognosis of gastric cancer patients.

19.
Modern Hospital ; (6): 1805-1808,1813, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1022144

ABSTRACT

Objective To explore the current implementation status and existing problems of direct settlement for chronic and special critical diseases in cross provincial outpatient service policies,propose improvement strategies and suggestions,pro-vide reference for further improving direct settlement for chronic and special critical diseases in cross provincial outpatient service policies,enhance patient satisfaction and convenience in seeking medical treatment,and jointly maintain the safety of medical in-surance funds.Methods Extract settlement data from chronic and special critical diseases in cross provincial outpatient service and medical insurance service platform data from S Hospital,collect and sort out the difficulties encountered in daily settlement,and analyze the problems and reasons in the implementation of settlement policies.Results Direct settlement for chronic and special critical diseases in cross provincial outpatient service has brought convenience to patients,with an increasing number of settlement personnel.However,there are still problems such as cumbersome settlement processes,low settlement personnel,ina-bility to settle certain diseases,unclear settlement policies for patients,limited number of medical institutions opened,and inac-curate settlement data.Conclusion Medical insurance departments and institutions at all levels need to work together to develop a unified list of outpatient treatment for chronic and special critical diseases,expand the scope of pilot diseases and medical insti-tutions,optimize settlement processes,strengthen information construction,strengthen policy promotion and personnel training,establish a regulatory mechanism of outpatient treatment for chronic and special critical diseases in remote locations.

20.
Chinese Journal of Zoonoses ; (12): 1130-1135, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1024866

ABSTRACT

Alveolar echinococcosis is a zoonotic parasitic disease caused by an infection with Echinococcosis multilocularis.The liver is the primary organ of alveolar echinococcosis.Alveolar echinococcosis is usually characterized by invasive growth and consequently iscalled"parasitic cancer."Resection of radical lesions is a preferred and effective treatment for hepatic alveolar echinococcosis.End-stage hepatic alveolar echinococcosis often occurs with parasiticcirrhosis,such as secondary biliary cirrhosis,congestive liver cirrhosis or Budd-Chiari syndrome.Few studies have examined hepatic multilocular echinococcosis leading to cirrhosis.This article reviews the aspects of hepatic alveolar echinococcosis involving the invasion of important blood vessels and bile ducts,thereby leading to secondary biliary cirrhosis and congestive liver cirrhosis caused by hepatic alveolar echinococcosis.

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