This study aimed to establish a highly accurate method for quantifying methotrexate(MTX)concentrations in serum using an ultra-high performance liquid chromatography-tandem mass spectrometry system(UPLC-MS/MS)and to c...This study aimed to establish a highly accurate method for quantifying methotrexate(MTX)concentrations in serum using an ultra-high performance liquid chromatography-tandem mass spectrometry system(UPLC-MS/MS)and to compare its performance with the chemiluminescence microparticle immunoassay(CMIA).A total of 211 serum samples from pediatric patients with intracranial tumors undergoing high-dose MTX treatment were analyzed using both techniques.Correlation and agreement analyses were performed to assess the level of concordance between these methods.The results demonstrated a significant correlation(P<0.05)between the two methods,with correlation coefficients of 0.9913 and 0.9893,respectively.However,a statistical difference was noted in MTX serum concentrations at lower levels(0.04-1.5μmol/L),while no significant difference was observed at higher concentrations(1.5-400μmol/L).Specifically,in the 0.04-1.5μmol/L range(107 cases),Bland-Altman analysis indicated a bias of 0.018 between the two methods.Given the observed discrepancies,particularly at lower concentrations,it is advised that the UPLC-MS/MS method should not be used interchangeably with the CMIA assay for therapeutic drug monitoring in patients receiving high-dose MTX treatment.展开更多
Identifying drug-drug interactions(DDIs)is essential to prevent adverse effects from polypharmacy.Although deep learning has advanced DDI identification,the gap between powerful models and their lack of clinical appli...Identifying drug-drug interactions(DDIs)is essential to prevent adverse effects from polypharmacy.Although deep learning has advanced DDI identification,the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits.Here,we developed a Multi-Dimensional Feature Fusion model named MDFF,which integrates one-dimensional simplified molec-ular input line entry system sequence features,two-dimensional molecular graph features,and three-dimensional geometric features to enhance drug representations for predicting DDIs.MDFF was trained and validated on two DDI datasets,evaluated across three distinct scenarios,and compared with advanced DDI prediction models using accuracy,precision,recall,area under the curve,and F1 score metrics.MDFF achieved state-of-the-art performance across all metrics.Ablation experiments showed that integrating multi-dimensional drug features yielded the best results.More importantly,we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs.Among 12 real-world adverse drug reaction reports,the predictions of 9 reports were supported by relevant evidence.Additionally,MDFF demon-strated the ability to explain adverse DDI mechanisms,providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.展开更多
Objective:Medical expulsive therapy(MET)is a suitable option for facilitating stone expulsion in patients with distal ureteral stones.This meta-analysis was conducted to compare efficacy and safety of monotherapy and ...Objective:Medical expulsive therapy(MET)is a suitable option for facilitating stone expulsion in patients with distal ureteral stones.This meta-analysis was conducted to compare efficacy and safety of monotherapy and combination therapy with tamsulosin,silodosin,and tadalafil on stone expulsion rate(SER)and stone expulsion time(SET),as well as their comparative safety,numbers of colic pain episodes,and need for analgesics.Methods:Randomized controlled trials were retrieved by searching PubMed,Scopus,and Web of Science up to November 27,2023.Hand-searching was also conducted in Google Scholar to find additional records.Papers in English that compared the safety and efficacy of at least two of the above agents in adults with distal ureteral stones≤10 mm were included.Results:In total,27 studies were identified(six studies through database searches and 21 through checking reference lists and hand-searching in Google Scholar).More than half of them(n=15,56%)were conducted in India.The SER significantly improved with silodosin compared with tamsulosin(odds ratio[OR]2.24,p<0.001),whereas the difference in SET was non-significant.Tadalafil achieved a significantly higher SER compared with tamsulosin(OR 1.42,p=0.042)without any difference in SET.Subgroup analysis of 5-and 10-mg doses of tadalafil showed no significant difference in SER or SET.We found no significant difference in need for analgesics(mean difference(MD−53.73,p=0.2)or the mean number of colic episodes(MD−0.42,p=0.060)between tadalafil and tamsulosin.SER or SET was not significantly different between silodosin and tadalafil.Tadalafil plus tamsulosin led to a significantly higher SER(OR 1.87,p<0.001)and SET(MD−2.99,p=0.002)compared with tamsulosin,without any significant difference in adverse effects.Conclusion:Compared with tamsulosin,SER significantly improved with silodosin,tadalafil,and the combination of tadalafil plus tamsulosin.Meanwhile,the difference in SET was only significant between tadalafil plus tamsulosin versus tamsulosin.It appears that tadalafil and silodosin have similar efficacy in SET and SER.All medical expulsive therapies had comparable safety.展开更多
Natural law is an important concept of the Westem political culture. The author makes a simple investigation into the various definitions of natural law, based on which he comes to the conclusion that natural law is a...Natural law is an important concept of the Westem political culture. The author makes a simple investigation into the various definitions of natural law, based on which he comes to the conclusion that natural law is a key concept of Western political culture; that it is a moral norm of politics as well as a product of rational thinking; and that its meaning has varied over time.展开更多
BACKGROUND The methylated septin 9(mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test.However, the diagnostic and prognostic role of ...BACKGROUND The methylated septin 9(mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test.However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer(CRC) in Chinese patients is still unknown.AIM To improve the understanding of diagnostic and prognostic factors, serum m SEPT9 was detected in Chinese CRC patients.METHODS A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal,was performed in China. Patients' characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control(UICC) stages, distant metastasis(M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas(TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival(OS) and progression-free survival(PFS)were evaluated by Kaplan-Meier univariate analysis.RESULTSIn Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages(I–IV), primary tumor categories(T1–T4),regional node categories(N0–N2), and distant metastasis categories(M0–M1).The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies.CONCLUSION MSEPT9 analysis may add valuable information to current tumor staging. Serum m SEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.展开更多
In the present study,we aimed to investigate the influence of CYP2C9^＊2 genetic polymorphism on pharmacokinetics of losartan and its active metabolite E-3174 on the background of CYP3A4 wild genotype in healthy Chine...In the present study,we aimed to investigate the influence of CYP2C9^＊2 genetic polymorphism on pharmacokinetics of losartan and its active metabolite E-3174 on the background of CYP3A4 wild genotype in healthy Chinese Hui subjects.Blood samples were collected from subjects for CYP2C9 and CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） assay.A pharmacokinetic study was then carried out in two groups with CYP2 C9^＊1/^＊1（n = 8） and CYP2 C9^＊1/^＊2（n = 6） genotypes at the same time,and all the 14 subjects were CYP3A4 wild genotype.Plasma levels of losartan and E-3174 were determined by high-performance liquid chromatography-fluorescence（HPLC-FLD） method before and after a single oral dose of 50-mg dose of losartan in tablet form.The pharmacokinetic parameters were calculated by DAS 2.0 software and analyzed by SPSS 16.0 software.Pharmacokinetic parameters,including area under the curve from 0 h to the last measured point 24 h（AUC0–24）,area under the curve from 0 h to infinite time（AUC0–∞）,peak plasma concentration（Cmax）,time to reach Cmax（tmax）,oral clearance（CL）,oral volume of distribution（Vd） and elimination half-life（t1/2）,were determined.Compared with the CYP2C9^＊1/^＊2 group,the AUC0–24,AUC0–∞ and Cmax of E-3174 in CYP2C9^＊1/^＊1 group of Hui subjects were respectively 1.36,1.32 and 1.64 times more,and the statistic differences were significant（P〈0.05）.The CYP2C9^＊2 mutant allele played an important role in the pharmacokinetics of losartan after oral administration,and it might decrease the generation of E-3174.However,large-sample clinical trials are required to validate whether the dose adjustment according to CYP2C9 genotype is necessary.展开更多
Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX conce...Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX concentrations and elimination delay in pediatric patients with hematological malignancies. Cycles of HD-MTX therapy were categorized into the normal elimination group and delayed elimination group according to the serum MTX concentrations at 24(C) or 42 h(C) after the start of MTX therapy. Clinical characteristics associated with MTX concentrations and elimination delay were assessed by χ^(2) test, Fisher’s exact test, Mann-Whitney test, or Spearman’s correlation coefficient. Generalized Estimating Equations(GEE) were used to adjust for the clustering effects of multiple cycles in one patient and confounders. A total of 43 patients with 138 cycles of HD-MTX chemotherapy were included and evaluated in the current study. Dose, white blood cells(WBC), hemoglobin(HB), and blood urea nitrogen(BUN) were significantly correlated with MTX C(all P < 0.05). No significant correlations were noticed between baseline characteristics and MTX C. Delayed MTX elimination was observed in 34(24.6%) courses. Dose, WBC, HB, BUN, and concurrent infection were the significant risk factors for delayed MTX elimination(all P < 0.05). Our study identified several risk factors associated with MTX levels and elimination, which might be used to recognize patients with a high risk of delayed MTX elimination. However, the findings need to be confirmed in further large-scale studies.展开更多
BACKGROUND The ratio of lymphocytes to monocytes(LMR)has been shown to be an effective predictor of gastric cancer prognosis.However,its predictive accuracy for signet ring gastric cancer is currently not well underst...BACKGROUND The ratio of lymphocytes to monocytes(LMR)has been shown to be an effective predictor of gastric cancer prognosis.However,its predictive accuracy for signet ring gastric cancer is currently not well understood.AIM To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer.METHODS A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University,Department of Gastrointestinal Surgery,from January 2012 to December 2016 were enrolled in the study.The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic.Factors that significantly affect the survival of patients were identified using single factor analysis,and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis.RESULTS The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors,including tumor invasion(χ^(2)=49.726;P<0.001),lymph node metastasis(χ^(2)=30.269;P<0.001),pTNM stage(χ^(2)=49.322;P<0.001),surgical approach(χ^(2)=8.489;P=0.004),age(t=-2.213;P<0.028),carcinoembryonic antigen(CEA)(Z=-3.265;P=0.001),platelet-to-lymphocyte ratio(Z=-2.196;P=0.028),LMR(Z=-2.226;P=0.026),ALB(t=3.284;P=0.001),prognostic nutritional index(t=-3.789;P<0.001)and FIB(Z=-3.065;P=0.002).Furthermore,the multivariate analysis further demonstrated that age(HR:0.563,95%CI:0.363-0.873),tumor invasion depth(HR:0.226,95%CI:0.098-0.520),pTNM stage(HR:0.444,95%CI:0.255-0.771),preoperative CEA level(HR:0.597,95%CI:0.386-8.790),and preoperative LMR level(HR:1.776,95%CI:1.150-2.741)were independent factors influencing the prognosis of signet ring gastric cancer.CONCLUSION In signet ring gastric cancer patients,a low preoperative LMR level predicts poor prognosis.The death risk ratio of the low LMR group compared to the high LMR group is 1.776.展开更多
Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality ...Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.展开更多
Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A...Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.展开更多
Background: So far, five types of prevention including: primordial, primary, secondary, tertiary and quaternary prevention levels have been defined in literatures. Aim: In this study, we have proposed “prevention of ...Background: So far, five types of prevention including: primordial, primary, secondary, tertiary and quaternary prevention levels have been defined in literatures. Aim: In this study, we have proposed “prevention of malpractice” as the other level of prevention. Methods: Qualitative comparison of the data, obtained from the review of conducted studies by using of scientific literatures, registered in PubMed, Google Scholar and Scopus sites. Results: Bringing dozens of examples of “malpractice” in the five areas of prevention. Conclusion: We concluded that, “malpractice” may be occurred at all levels of prevention and preventing it can be considered as the other level of prevention.展开更多
Background: Respiratory disorders are the most common diseases among Iranian pilgrims in Hajj. Some studies recommended flu and pneumococcal vaccines separately or in combination to reduce respiratory diseases occurre...Background: Respiratory disorders are the most common diseases among Iranian pilgrims in Hajj. Some studies recommended flu and pneumococcal vaccines separately or in combination to reduce respiratory diseases occurrence and its morbidity. These effects are not clear in afflicted Hajj pilgrims. Objective: This is a cohort study that investigates the effects of above-mentioned vaccines each or their combination on respiratory syndromes and their consequences among Iranian pilgrims in Mecca. Method: The participants were 295 Iranian pilgrims from the beginning to the end of the journey. They were systematically observed for getting afflicted with a respiratory syndrome or not. In this study, we have assessed the effects of flu and pneumococcal vaccines on respiratory disease occurrence and on 8 clinical consequences including as: the duration of fever, duration of cough, duration of bed rest, presence of post nasal discharge and dirty sputum, the total disease length, and the number of referrals to the hospital, physician’s visits and complications. The data for this study were gathered through a questionnaire with 14 basic questions and 60 choices. This was processed using the SPSS software of 11.5 version, T- and Chi-square tests. Results: The results showed no significant correlations between the above-mentioned factors and vaccination with one or both flu and pneumovax-23 except for the duration of coughs which was significantly reduced in all cases (p < 0.01) and also decreased complications of the disease (p < 0.001). Conclusion: The study suggests the high-risk groups, should be vaccinated with combination of flu and pneumovax-23 vaccines in Hajj.展开更多
Since the mercantilism era, economists have built up trade theories to explain the rationale and patterns of world trade.In this paper, the explanatory power of the international product life cycle (IPLC) theory for d...Since the mercantilism era, economists have built up trade theories to explain the rationale and patterns of world trade.In this paper, the explanatory power of the international product life cycle (IPLC) theory for describing the trends and patterns of the global textile trade, one of the most geographically dispersed export items in both developed and developing countries/regions, is discussed. Data at SITC two-digit level (SITC 65 ) were collected and time series regressions were performed to analyze the value trends and world shares of textile exports from 1990 to 2000 for selected developed economies. It was found that some developed economies have increased their world shares in textile exports, which indicated that global trade shift in the textile industry may not follow what the IPLC has suggested.展开更多
Quality marker(Q-marker)of Chinese materia medica(CMM)plays an important role in quality control of CMM products.However,its research strategy and technique remain unclear.Based on the fact that quality standard of CM...Quality marker(Q-marker)of Chinese materia medica(CMM)plays an important role in quality control of CMM products.However,its research strategy and technique remain unclear.Based on the fact that quality standard of CMM should be associated with clinical efficacy,taking Jinqi Jiangtang tablet treating type 2 diabetes as an example,the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated.Therefore,we proposed a new research strategy of Q-marker of CMM with"Discovery of clinical active constituents as guidance,Reverse analysis of metabolic transformations as link,and Traceability of biosynthesis pathways as key",to improve quality control of CMM products.展开更多
Solar-induced skin damage continues to pose a problem to human health worldwide, despite the widespread recommendation and use of sunscreens. We have previously reported that solar visible light and near-infrared also...Solar-induced skin damage continues to pose a problem to human health worldwide, despite the widespread recommendation and use of sunscreens. We have previously reported that solar visible light and near-infrared also contribute to skin damage and photoageing. Most commonly recommended sunscreens are only effective throughout the UV spectrum, offering no protection from visible light and near-infrared. To evaluate the enhanced solar-spectrum blocking ability of iron oxides, a double-beam spectrophotometer was used to optically measure the transmission spectra. The spectrophotometer deploys a unique, single monochromatic design to detect wavelength penetration in the range of 240 to 2600 nm. The sample without iron oxide (control) blocked over 80% of ultraviolet-C and ultraviolet-B but did not block ultraviolet-A, visible light, or near-infrared wavelengths. The samples with yellow, and red iron oxide blocked over 90% ultraviolet, but did not block visible light and near-infrared effectively. The sample with black iron oxide blocked visible light, and near-infrared effectively compared with other samples with yellow, blue, and red iron oxide. The sample with red and black iron oxides, and the sample with yellow, blue, red, and black iron oxides blocked ultraviolet through to near-infrared. It can be concluded that dark colored iron oxide combinations are effective at blocking from ultraviolet through to visible light and near-infrared radiation. The results of this study may also suggest that biological colour of human skin and subcutaneous tissues are conserved for comprehensive photoprotection.展开更多
Background: While sunscreen has been accepted as a mainline defence against photodamage from ultraviolet, visible light and near-infrared radiation, there appears to be a lack of research into photorepair. The concept...Background: While sunscreen has been accepted as a mainline defence against photodamage from ultraviolet, visible light and near-infrared radiation, there appears to be a lack of research into photorepair. The concept of protecting the skin during the day and repairing cellular damage at night is intuitive, yet specific strategies revolving around combinations of proven reparative active ingredients remain unelucidated. Purpose: To investigate the efficacy of a solar repair Formulation following ultraviolet and environmental exposure in order to improve overall skin health and appearance through three hypotheses: The Formulation increases expression of DNA repair mechanisms markers;The Formulation enhances overall skin appearance through reducing signs of inflammation, elevating hydration, reinforcing skin firmness and amplifying radiance;In-Vivo efficacy test results are aligned with measured gene expression changes. Methods: The Formulation (#6NIC1.V1.1-1) was tested for: In-vitro LDH cytotoxicity activity, In-vitro qPCR gene expression with and without ultraviolet exposure on a reconstructed 3-dimensional skin model, and In-Vivo efficacy study on a panel of 22 participants objectively and subjectively. Results: Skin radiance, firmness, hydration, redness, and inflammation are significantly improved after In-Vivo skin exposure to the Formulation and environmental challenges such as ultraviolet radiation. These outcomes were confirmed by in-vitro genetic testing on a reconstructed human skin model. Conclusion: The studies allowed us to identify and group results in four main skin functions that were significantly enhanced following the application of the Formulation: firmness, hydration, radiance and soothing.展开更多
Despite the widespread recommendation and use of sunscreens and ultraviolet blocking materials, solar-induced skin damage and photoageing continues to pose a problem to human health worldwide. We have previously repor...Despite the widespread recommendation and use of sunscreens and ultraviolet blocking materials, solar-induced skin damage and photoageing continues to pose a problem to human health worldwide. We have previously reported that solar visible light and near-infrared also contribute to skin damage and photo ageing. Most commonly recommended sunscreens are only effective throughout the UV spectrum, offering no protection from visible light and near-infrared. A possible solution could be to augment sunscreens with metal oxides which block visible light and near-infrared radiation. To evaluate the enhanced solar-spectrum blocking ability of novel low viscosity sunscreen containing zinc and iron oxides, a double-beam spectrophotometer was used to optically measure the transmission spectra. The spectrophotometer deploys a unique, single monochromatic design to detect wavelength penetration in the range of 240 to 2600 nm. The Sunscreen base without zinc oxide and iron oxides (control) blocked over 80% of ultraviolet-C and ultraviolet-B but did not block ultraviolet-A, visible light, or near-infrared. The novel low viscosity zinc oxide sample blocked almost over 90% ultraviolet, but did not block visible light and near-infrared sufficiently. However, the samples with the novel low viscosity zinc oxide, iron oxides and erioglaucine blocked almost over 90% of ultraviolet, visible light and near-infrared. It can be concluded that this novel combination of low viscosity zinc oxide, iron oxides and erioglaucine is effective at blocking ultraviolet, visible light and near-infrared radiation. The results of this study imply that sunscreens that provide comprehensive photoprotection from ultraviolet through to near-infrared should be adopted to prevent skin photodamage.展开更多
基金The Science and Technology Fund of Beijing Shijitan Hospital(Grant No.2022-C06)the National Key Research and Development Program of China(Grant No.2020YFF01014606).
文摘This study aimed to establish a highly accurate method for quantifying methotrexate(MTX)concentrations in serum using an ultra-high performance liquid chromatography-tandem mass spectrometry system(UPLC-MS/MS)and to compare its performance with the chemiluminescence microparticle immunoassay(CMIA).A total of 211 serum samples from pediatric patients with intracranial tumors undergoing high-dose MTX treatment were analyzed using both techniques.Correlation and agreement analyses were performed to assess the level of concordance between these methods.The results demonstrated a significant correlation(P<0.05)between the two methods,with correlation coefficients of 0.9913 and 0.9893,respectively.However,a statistical difference was noted in MTX serum concentrations at lower levels(0.04-1.5μmol/L),while no significant difference was observed at higher concentrations(1.5-400μmol/L).Specifically,in the 0.04-1.5μmol/L range(107 cases),Bland-Altman analysis indicated a bias of 0.018 between the two methods.Given the observed discrepancies,particularly at lower concentrations,it is advised that the UPLC-MS/MS method should not be used interchangeably with the CMIA assay for therapeutic drug monitoring in patients receiving high-dose MTX treatment.
基金supported by the National Key R&D Program of China(Grant No.:2023YFC2604400)the National Natural Science Foundation of China(Grant No.:62103436).
文摘Identifying drug-drug interactions(DDIs)is essential to prevent adverse effects from polypharmacy.Although deep learning has advanced DDI identification,the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits.Here,we developed a Multi-Dimensional Feature Fusion model named MDFF,which integrates one-dimensional simplified molec-ular input line entry system sequence features,two-dimensional molecular graph features,and three-dimensional geometric features to enhance drug representations for predicting DDIs.MDFF was trained and validated on two DDI datasets,evaluated across three distinct scenarios,and compared with advanced DDI prediction models using accuracy,precision,recall,area under the curve,and F1 score metrics.MDFF achieved state-of-the-art performance across all metrics.Ablation experiments showed that integrating multi-dimensional drug features yielded the best results.More importantly,we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs.Among 12 real-world adverse drug reaction reports,the predictions of 9 reports were supported by relevant evidence.Additionally,MDFF demon-strated the ability to explain adverse DDI mechanisms,providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.
文摘Objective:Medical expulsive therapy(MET)is a suitable option for facilitating stone expulsion in patients with distal ureteral stones.This meta-analysis was conducted to compare efficacy and safety of monotherapy and combination therapy with tamsulosin,silodosin,and tadalafil on stone expulsion rate(SER)and stone expulsion time(SET),as well as their comparative safety,numbers of colic pain episodes,and need for analgesics.Methods:Randomized controlled trials were retrieved by searching PubMed,Scopus,and Web of Science up to November 27,2023.Hand-searching was also conducted in Google Scholar to find additional records.Papers in English that compared the safety and efficacy of at least two of the above agents in adults with distal ureteral stones≤10 mm were included.Results:In total,27 studies were identified(six studies through database searches and 21 through checking reference lists and hand-searching in Google Scholar).More than half of them(n=15,56%)were conducted in India.The SER significantly improved with silodosin compared with tamsulosin(odds ratio[OR]2.24,p<0.001),whereas the difference in SET was non-significant.Tadalafil achieved a significantly higher SER compared with tamsulosin(OR 1.42,p=0.042)without any difference in SET.Subgroup analysis of 5-and 10-mg doses of tadalafil showed no significant difference in SER or SET.We found no significant difference in need for analgesics(mean difference(MD−53.73,p=0.2)or the mean number of colic episodes(MD−0.42,p=0.060)between tadalafil and tamsulosin.SER or SET was not significantly different between silodosin and tadalafil.Tadalafil plus tamsulosin led to a significantly higher SER(OR 1.87,p<0.001)and SET(MD−2.99,p=0.002)compared with tamsulosin,without any significant difference in adverse effects.Conclusion:Compared with tamsulosin,SER significantly improved with silodosin,tadalafil,and the combination of tadalafil plus tamsulosin.Meanwhile,the difference in SET was only significant between tadalafil plus tamsulosin versus tamsulosin.It appears that tadalafil and silodosin have similar efficacy in SET and SER.All medical expulsive therapies had comparable safety.
文摘Natural law is an important concept of the Westem political culture. The author makes a simple investigation into the various definitions of natural law, based on which he comes to the conclusion that natural law is a key concept of Western political culture; that it is a moral norm of politics as well as a product of rational thinking; and that its meaning has varied over time.
基金Supported by the National Natural Science Foundation of China,No.81803035,No.81703036,and No.81572946the China Postdoctoral Science Foundation,No.2017M610510the Youth Fund of Xiangya Hospital,No.2017Q17
文摘BACKGROUND The methylated septin 9(mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test.However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer(CRC) in Chinese patients is still unknown.AIM To improve the understanding of diagnostic and prognostic factors, serum m SEPT9 was detected in Chinese CRC patients.METHODS A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal,was performed in China. Patients' characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control(UICC) stages, distant metastasis(M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas(TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival(OS) and progression-free survival(PFS)were evaluated by Kaplan-Meier univariate analysis.RESULTSIn Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages(I–IV), primary tumor categories(T1–T4),regional node categories(N0–N2), and distant metastasis categories(M0–M1).The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies.CONCLUSION MSEPT9 analysis may add valuable information to current tumor staging. Serum m SEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.
基金A Research Grant from the 115 Project of Legionary Medical Treatment and Public Health(Grant No.06G023)
文摘In the present study,we aimed to investigate the influence of CYP2C9^＊2 genetic polymorphism on pharmacokinetics of losartan and its active metabolite E-3174 on the background of CYP3A4 wild genotype in healthy Chinese Hui subjects.Blood samples were collected from subjects for CYP2C9 and CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） assay.A pharmacokinetic study was then carried out in two groups with CYP2 C9^＊1/^＊1（n = 8） and CYP2 C9^＊1/^＊2（n = 6） genotypes at the same time,and all the 14 subjects were CYP3A4 wild genotype.Plasma levels of losartan and E-3174 were determined by high-performance liquid chromatography-fluorescence（HPLC-FLD） method before and after a single oral dose of 50-mg dose of losartan in tablet form.The pharmacokinetic parameters were calculated by DAS 2.0 software and analyzed by SPSS 16.0 software.Pharmacokinetic parameters,including area under the curve from 0 h to the last measured point 24 h（AUC0–24）,area under the curve from 0 h to infinite time（AUC0–∞）,peak plasma concentration（Cmax）,time to reach Cmax（tmax）,oral clearance（CL）,oral volume of distribution（Vd） and elimination half-life（t1/2）,were determined.Compared with the CYP2C9^＊1/^＊2 group,the AUC0–24,AUC0–∞ and Cmax of E-3174 in CYP2C9^＊1/^＊1 group of Hui subjects were respectively 1.36,1.32 and 1.64 times more,and the statistic differences were significant（P〈0.05）.The CYP2C9^＊2 mutant allele played an important role in the pharmacokinetics of losartan after oral administration,and it might decrease the generation of E-3174.However,large-sample clinical trials are required to validate whether the dose adjustment according to CYP2C9 genotype is necessary.
基金National Natural Science Foundation of China (Grant No. 81872926 and No. 81503135)Beijing Municipal Administration of Hospitals’ Youth Programme (Grant No. QML20160703)+1 种基金Enhancement Fun ding of Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use (BZ0439)Science and Technology Fund of Beijing Shijitan Hospital (Grant No. 2017-c01)。
文摘Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX concentrations and elimination delay in pediatric patients with hematological malignancies. Cycles of HD-MTX therapy were categorized into the normal elimination group and delayed elimination group according to the serum MTX concentrations at 24(C) or 42 h(C) after the start of MTX therapy. Clinical characteristics associated with MTX concentrations and elimination delay were assessed by χ^(2) test, Fisher’s exact test, Mann-Whitney test, or Spearman’s correlation coefficient. Generalized Estimating Equations(GEE) were used to adjust for the clustering effects of multiple cycles in one patient and confounders. A total of 43 patients with 138 cycles of HD-MTX chemotherapy were included and evaluated in the current study. Dose, white blood cells(WBC), hemoglobin(HB), and blood urea nitrogen(BUN) were significantly correlated with MTX C(all P < 0.05). No significant correlations were noticed between baseline characteristics and MTX C. Delayed MTX elimination was observed in 34(24.6%) courses. Dose, WBC, HB, BUN, and concurrent infection were the significant risk factors for delayed MTX elimination(all P < 0.05). Our study identified several risk factors associated with MTX levels and elimination, which might be used to recognize patients with a high risk of delayed MTX elimination. However, the findings need to be confirmed in further large-scale studies.
基金the Clinical Research Fund of National Geriatric Disease Clinical Medical Research Center,No.2022LNJ22Guangdong Yiyang Healthcare Charity Foundation,No.JZ2022014.
文摘BACKGROUND The ratio of lymphocytes to monocytes(LMR)has been shown to be an effective predictor of gastric cancer prognosis.However,its predictive accuracy for signet ring gastric cancer is currently not well understood.AIM To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer.METHODS A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University,Department of Gastrointestinal Surgery,from January 2012 to December 2016 were enrolled in the study.The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic.Factors that significantly affect the survival of patients were identified using single factor analysis,and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis.RESULTS The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors,including tumor invasion(χ^(2)=49.726;P<0.001),lymph node metastasis(χ^(2)=30.269;P<0.001),pTNM stage(χ^(2)=49.322;P<0.001),surgical approach(χ^(2)=8.489;P=0.004),age(t=-2.213;P<0.028),carcinoembryonic antigen(CEA)(Z=-3.265;P=0.001),platelet-to-lymphocyte ratio(Z=-2.196;P=0.028),LMR(Z=-2.226;P=0.026),ALB(t=3.284;P=0.001),prognostic nutritional index(t=-3.789;P<0.001)and FIB(Z=-3.065;P=0.002).Furthermore,the multivariate analysis further demonstrated that age(HR:0.563,95%CI:0.363-0.873),tumor invasion depth(HR:0.226,95%CI:0.098-0.520),pTNM stage(HR:0.444,95%CI:0.255-0.771),preoperative CEA level(HR:0.597,95%CI:0.386-8.790),and preoperative LMR level(HR:1.776,95%CI:1.150-2.741)were independent factors influencing the prognosis of signet ring gastric cancer.CONCLUSION In signet ring gastric cancer patients,a low preoperative LMR level predicts poor prognosis.The death risk ratio of the low LMR group compared to the high LMR group is 1.776.
基金The National Natural Science Foundation of China (grant number 81773891)the National Great New Drugs Development Project of China (grant number 2017ZX09301-040)+1 种基金the Beijing Municipal Science and Technology Commission (grant number XMLX201704, 2018-2-2242, 7194280)the Open Research Fund of the State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicinal Resources.
文摘Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.
基金supported by the National Key Research and Development Program of China(No.2020YFF01014606)the National Natural Science Foundation of China(No.82073741).
文摘Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.
文摘Background: So far, five types of prevention including: primordial, primary, secondary, tertiary and quaternary prevention levels have been defined in literatures. Aim: In this study, we have proposed “prevention of malpractice” as the other level of prevention. Methods: Qualitative comparison of the data, obtained from the review of conducted studies by using of scientific literatures, registered in PubMed, Google Scholar and Scopus sites. Results: Bringing dozens of examples of “malpractice” in the five areas of prevention. Conclusion: We concluded that, “malpractice” may be occurred at all levels of prevention and preventing it can be considered as the other level of prevention.
文摘Background: Respiratory disorders are the most common diseases among Iranian pilgrims in Hajj. Some studies recommended flu and pneumococcal vaccines separately or in combination to reduce respiratory diseases occurrence and its morbidity. These effects are not clear in afflicted Hajj pilgrims. Objective: This is a cohort study that investigates the effects of above-mentioned vaccines each or their combination on respiratory syndromes and their consequences among Iranian pilgrims in Mecca. Method: The participants were 295 Iranian pilgrims from the beginning to the end of the journey. They were systematically observed for getting afflicted with a respiratory syndrome or not. In this study, we have assessed the effects of flu and pneumococcal vaccines on respiratory disease occurrence and on 8 clinical consequences including as: the duration of fever, duration of cough, duration of bed rest, presence of post nasal discharge and dirty sputum, the total disease length, and the number of referrals to the hospital, physician’s visits and complications. The data for this study were gathered through a questionnaire with 14 basic questions and 60 choices. This was processed using the SPSS software of 11.5 version, T- and Chi-square tests. Results: The results showed no significant correlations between the above-mentioned factors and vaccination with one or both flu and pneumovax-23 except for the duration of coughs which was significantly reduced in all cases (p < 0.01) and also decreased complications of the disease (p < 0.001). Conclusion: The study suggests the high-risk groups, should be vaccinated with combination of flu and pneumovax-23 vaccines in Hajj.
文摘Since the mercantilism era, economists have built up trade theories to explain the rationale and patterns of world trade.In this paper, the explanatory power of the international product life cycle (IPLC) theory for describing the trends and patterns of the global textile trade, one of the most geographically dispersed export items in both developed and developing countries/regions, is discussed. Data at SITC two-digit level (SITC 65 ) were collected and time series regressions were performed to analyze the value trends and world shares of textile exports from 1990 to 2000 for selected developed economies. It was found that some developed economies have increased their world shares in textile exports, which indicated that global trade shift in the textile industry may not follow what the IPLC has suggested.
基金the National Natural Science Foundation of China(81773891)the National Great New Drugs Development Project of China(2017ZX09301-040)+3 种基金the Beijing Natural Science Foundation(7162092)Beijing Talents Project(2017A19)Beijing Municipal Science&Technology Commission(XMLX201704,Z161100000516074)the Open Research Fund of the State Key Laboratory Breeding Base of Systematic Research,Development and Utilization of Chinese Medicinal Resources.
文摘Quality marker(Q-marker)of Chinese materia medica(CMM)plays an important role in quality control of CMM products.However,its research strategy and technique remain unclear.Based on the fact that quality standard of CMM should be associated with clinical efficacy,taking Jinqi Jiangtang tablet treating type 2 diabetes as an example,the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated.Therefore,we proposed a new research strategy of Q-marker of CMM with"Discovery of clinical active constituents as guidance,Reverse analysis of metabolic transformations as link,and Traceability of biosynthesis pathways as key",to improve quality control of CMM products.
文摘Solar-induced skin damage continues to pose a problem to human health worldwide, despite the widespread recommendation and use of sunscreens. We have previously reported that solar visible light and near-infrared also contribute to skin damage and photoageing. Most commonly recommended sunscreens are only effective throughout the UV spectrum, offering no protection from visible light and near-infrared. To evaluate the enhanced solar-spectrum blocking ability of iron oxides, a double-beam spectrophotometer was used to optically measure the transmission spectra. The spectrophotometer deploys a unique, single monochromatic design to detect wavelength penetration in the range of 240 to 2600 nm. The sample without iron oxide (control) blocked over 80% of ultraviolet-C and ultraviolet-B but did not block ultraviolet-A, visible light, or near-infrared wavelengths. The samples with yellow, and red iron oxide blocked over 90% ultraviolet, but did not block visible light and near-infrared effectively. The sample with black iron oxide blocked visible light, and near-infrared effectively compared with other samples with yellow, blue, and red iron oxide. The sample with red and black iron oxides, and the sample with yellow, blue, red, and black iron oxides blocked ultraviolet through to near-infrared. It can be concluded that dark colored iron oxide combinations are effective at blocking from ultraviolet through to visible light and near-infrared radiation. The results of this study may also suggest that biological colour of human skin and subcutaneous tissues are conserved for comprehensive photoprotection.
文摘Background: While sunscreen has been accepted as a mainline defence against photodamage from ultraviolet, visible light and near-infrared radiation, there appears to be a lack of research into photorepair. The concept of protecting the skin during the day and repairing cellular damage at night is intuitive, yet specific strategies revolving around combinations of proven reparative active ingredients remain unelucidated. Purpose: To investigate the efficacy of a solar repair Formulation following ultraviolet and environmental exposure in order to improve overall skin health and appearance through three hypotheses: The Formulation increases expression of DNA repair mechanisms markers;The Formulation enhances overall skin appearance through reducing signs of inflammation, elevating hydration, reinforcing skin firmness and amplifying radiance;In-Vivo efficacy test results are aligned with measured gene expression changes. Methods: The Formulation (#6NIC1.V1.1-1) was tested for: In-vitro LDH cytotoxicity activity, In-vitro qPCR gene expression with and without ultraviolet exposure on a reconstructed 3-dimensional skin model, and In-Vivo efficacy study on a panel of 22 participants objectively and subjectively. Results: Skin radiance, firmness, hydration, redness, and inflammation are significantly improved after In-Vivo skin exposure to the Formulation and environmental challenges such as ultraviolet radiation. These outcomes were confirmed by in-vitro genetic testing on a reconstructed human skin model. Conclusion: The studies allowed us to identify and group results in four main skin functions that were significantly enhanced following the application of the Formulation: firmness, hydration, radiance and soothing.
文摘Despite the widespread recommendation and use of sunscreens and ultraviolet blocking materials, solar-induced skin damage and photoageing continues to pose a problem to human health worldwide. We have previously reported that solar visible light and near-infrared also contribute to skin damage and photo ageing. Most commonly recommended sunscreens are only effective throughout the UV spectrum, offering no protection from visible light and near-infrared. A possible solution could be to augment sunscreens with metal oxides which block visible light and near-infrared radiation. To evaluate the enhanced solar-spectrum blocking ability of novel low viscosity sunscreen containing zinc and iron oxides, a double-beam spectrophotometer was used to optically measure the transmission spectra. The spectrophotometer deploys a unique, single monochromatic design to detect wavelength penetration in the range of 240 to 2600 nm. The Sunscreen base without zinc oxide and iron oxides (control) blocked over 80% of ultraviolet-C and ultraviolet-B but did not block ultraviolet-A, visible light, or near-infrared. The novel low viscosity zinc oxide sample blocked almost over 90% ultraviolet, but did not block visible light and near-infrared sufficiently. However, the samples with the novel low viscosity zinc oxide, iron oxides and erioglaucine blocked almost over 90% of ultraviolet, visible light and near-infrared. It can be concluded that this novel combination of low viscosity zinc oxide, iron oxides and erioglaucine is effective at blocking ultraviolet, visible light and near-infrared radiation. The results of this study imply that sunscreens that provide comprehensive photoprotection from ultraviolet through to near-infrared should be adopted to prevent skin photodamage.
