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Comparative Fasting Bioavailability of Two Letrozole 2.5-mg Tablets in Healthy Chinese Postmenopausal Women:An Open-Label,Randomized-Sequence,Single-Dose,Two-Way Crossover study

Comparative Fasting Bioavailability of Two Letrozole 2.5-mg ...

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第十三次全国临床药理学学术大会

作者： Yi Liu,MS~1 Yifan Zhang,phd~2 Qian Wang,MS~1 Wei Yang,MS~1 Xiaoyan Chen,phd~2 Shan Jing,MD~1 Libo Zhao,phd~1 Lihui Wei,MD~3 Xiaoping Li,MD~3 Wanyu Feng,phd~1 dafang zhong,phd~2 and Yi Fang,phd~1 1 Department of Pharmacy,Peking University People’s Hospital,Beijing,100044,People’s Republic of China 2 Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,People’s Republic of China 3 Department of Gynecology,Peking University People’s Hospital,Beijing,100044,People’s Republic of China

Background:Letrozole is an orally active aromatase inhibitor indicated for the treatment of postmenopausal women with breast *** the bioavailability and pharmacokinetic(PK) properties of letrozole have been examined in western populations and healthy Chinese men,a literature search did not identify any reports concerning the bioavailability and PK properties of letrozole in a population of healthy Chinese postmenopausal women. Objective:The study was designed to assess and compare the PK properties and bioequivalence of two 2.5-mg tablets of letrozole:the newly developed generic formulation(test) and a branded formulation(reference) in healthy Chinese postmenopausal women. Methods:A single-dose,randomized,open-label,two-way crossover study was conducted in healthy Chinese postmenopausal women under fasting *** participants were randomly assigned to receive 1 tablet(2.5 mg each) of the test or reference formulation,followed by a 21-day washout period and administration of the alternate *** samples were collected before dosing and at 0.25,0.50,0.75, 1.00,1.25,1.50,2.00,2.50,3.00,3.50,4.00,6.00,8.00,12.00,24.00,48.00,72.00,96.00,144.00,192.00 and 240.00 hours after *** concentrations of letrozole were analyzed with a LC-MS/MS *** safety profile was evaluated by recording adverse events(AEs),assessed using physical examination,vital signs, spontaneous reporting,and clinical laboratory *** two formulations were considered bioequivalent if the 90%CIs for the In-transformed rations of C and AUC values were within the predetermined equivalence range (80%-125%). Results:A total of 30 healthy Chinese postmenopausal women were enrolled in this study;however,only the data from 29 subjects were included(mean[SD]age,54.9[4.7]years;weight,56.4[4.6]kg;height,158.7[4.8] cm;BMI,22.4[1.4]kg/m) in the PK and bioequivalence assessments due to serious adverse events(SAEs) occurred in one *** 90%CIs for the In-tra

关键词： Letrozole bioequivalence pharmacokinetics LC-MS/MS Chinese postmenopausal women

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C-X-C chemokine receptor type 5+CD8+T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferonalpha treatment

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World Journal of Gastroenterology 2025年第3期31卷 73-83页

作者： Zhen-Yu Xu zhong-Shang Dai Guo-zhong Gong Min Zhang Department of Infectious Diseases Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina Institute of Hepatology and Department of Infectious Diseases The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

BACKGROUND C-X-C chemokine receptor type 5(CXCR5)+CD8+T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell *** their importance,the specific role of CXCR5+CD8+T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully *** study aims to elucidate the relationship between CXCR5+CD8+T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for *** To elucidate the relationship between CXCR5+CD8+T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for *** This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α*** were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×104 copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of *** samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8+T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell *** Patients with CHB exhibited significantly lower levels of circulating CXCR5+CD8+T cells compared to healthy controls(P2).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.62

关键词： C-X-C chemokine receptor type 5 Programmed death-ligand 1 Interleukin-21 Pegylated interferon-alpha Chronic hepatitis B

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Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum

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Journal of Pharmaceutical Analysis 2021年第4期11卷 472-479页

作者： Yuxiong Gao Zhendong Chen Changyong Yang dafang zhong State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201210China University of Chinese Academy of Sciences Beijing100049China Preclinical Department Hengrui Medicine Co.Ltd.LianyungangJiangsu Province222047China

Liquid chromatography tandem mass spectrometry(LC-MS/MS)has gradually become a promising alternative to ligand binding assay for the bioanalysis of biotherapeutic molecules,due to its rapid method development and high *** this study,we established a new LC-MS/MS method for the determination of the anti-sclerostin monoclonal antibody(SHR-1222)in cynomolgus monkey serum,and compared it to a previous electrochemiluminescence *** antibody was quantified by detecting the surrogate peptide obtained by trypsin *** surrogate peptide was carefully selected by investigating its uniqueness,stability and MS *** quantitative range of the proposed method was 2.00-500μg/mL,and this verified method was successfully applied to the toxicokinetic assessment of SHR-1222 in cynomolgus monkey *** was found that the concentrations of SHR-1222 in cynomolgus monkeys displayed an excellent agreement between the LC-MS/MS and electrochemiluminescence methods(ratios of drug exposure,0.8-1.0).Notably,two monkeys in the60 mg/kg dose group had abnormal profiles with a low detection value of SHR-1222 in their individual *** the high-level anti-drug antibodies(ADAs)in these samples and the consistent quantitative results of the two methods,we found that the decreased concentration of SHR-1222 was due to the accelerated clearance mediated by ADAs rather than the interference of ADAs to the detection *** together,we successfully developed an accurate,efficient and cost-effective LC-MS/MS method for the quantification of SHR-1222 in serum samples,which could serve as a powerful tool to improve the preclinical development of antibody drugs.

关键词： Anti-sclerostin monoclonal antibody (SHR-1222) LC-MS/MS Anti-drug antibody Toxicokinetic

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Exploring the performance of large language models on hepatitis B infection-related questions:A comparative study

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World Journal of Gastroenterology 2025年第3期31卷 103-112页

作者： Yu Li Chen-Kai Huang Yi Hu Xiao-Dong Zhou Cong He Jia-Wei zhong Department of Gastroenterology Jiangxi Provincial Key Laboratory of Digestive DiseasesJiangxi Clinical Research Center for GastroenterologyDigestive Disease HospitalThe First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina HuanKui Academy Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Patients with hepatitis B virus(HBV)infection require chronic and personalized care to improve *** language models(LLMs)can potentially provide medical information for *** To examine the performance of three LLMs,ChatGPT-3.5,ChatGPT-4.0,and Google Gemini,in answering HBV-related *** LLMs’responses to HBV-related questions were independently graded by two medical professionals using a four-point accuracy scale,and disagreements were resolved by a third *** question was run three times using three *** was assessed via the Gunning Fog index and Flesch-Kincaid grade *** Overall,all three LLM chatbots achieved high average accuracy scores for subjective questions(ChatGPT-3.5:3.50;ChatGPT-4.0:3.69;Google Gemini:3.53,out of a maximum score of 4).With respect to objective questions,ChatGPT-4.0 achieved an 80.8%accuracy rate,compared with 62.9%for ChatGPT-3.5 and 73.1%for Google *** the six domains,ChatGPT-4.0 performed better in terms of diagnosis,whereas Google Gemini demonstrated excellent clinical ***,in the readability analysis,the mean Gunning Fog index and Flesch-Kincaid grade level scores of the three LLM chatbots were significantly higher than the standard level eight,far exceeding the reading level of the normal *** Our results highlight the potential of LLMs,especially ChatGPT-4.0,for delivering responses to HBV-related *** may be an adjunctive informational tool for patients and physicians to improve ***,current LLMs should not replace personalized treatment recommendations from physicians in the management of HBV infection.

关键词： ChatGPT-3.5 ChatGPT-4.0 Google Gemini Hepatitis B infection Accuracy

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Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 176-198页

作者： zhong-Xia Yang Li-Ting Zhang Xiao-Jun Liu Xue-Bin Peng Xiao-Rong Mao The First School of Clinical Medicine Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Infectious Diseases The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Radiotherapy Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal *** has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor *** regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy ***-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different *** hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in *** upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow *** studies were conducted with gene knockout models and pathway *** function of IL-17A in immune evasion was explored through coculture of T cells and HCC *** effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in *** IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by ***-17A enhanced the survival of HCC cells in the coculture ***-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic *** D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression *** combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse *** IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against

关键词： Interleukin-17A Programmed death ligand-1 Interleukin-17A receptor Small mothers against decapentaplegic 2 Hepatocellular carcinoma Immunotherapy

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Determination of ginsenoside compound K in human plasma by liquid chromatography–tandem mass spectrometry of lithium adducts

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Acta Pharmaceutica Sinica B 2015年第5期5卷 461-466页

作者： Yunhui Chen Youming Lu Yong Yang Xiaoyan Chen Liang Zhu dafang zhong Guangdong College of Pharmacy Shanghai Institute of Materia Medica Chinese Academy of Sciences

Ginsenoside compound K(GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography–tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel(internal standard) were extracted from 50 m L human plasma using methyl tertbutyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column(50 mm 2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile–water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 m L/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629-449 for the GCK-lithium adduct and m/z 860-292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00–1000 ng/m L(r^2>40.9988)with intra- and inter-day precision of ±8.4% and accuracy in the range of 4.8% to 6.5%. Recovery,stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers.

关键词： LC MS/MS Ginsenoside compound K Lithium adduct ion Pharmacokinetics

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Variations of plant life form diversity along the Northeast China Transect and its direct gradient analysis

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Journal of Environmental Sciences 2002年第4期14卷 547-551页

作者： WANGRen-zhong GAOQiong2 TANGHai-ping： LaboratoryofQuantitativeVegetationEcology InstituteofBotanyChineseAcademyofSciencesBeijing100093China InstituteofResourcesScience BeijingNormalUniversityBeijing100875China

Plant life form diversity and its direct gradient analysis on a larger scale climate change gradient were tested, based on the data from Northeast China Transect platform. The results showed that the species numbers, life form richness and life form diversity were relative higher at the eastern forests and the ecotone between typical vegetation, while those on the meadow grasslands and typical steppes were lower. Although plant life forms can reflect the climate variations, life form diversity is not consistent with the major global gradient along the NECT.

关键词： northeast China transect plant life form diversity ecotone gradient analysis

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Dynamic Regulation of Hydrogen Bonding Networks and Solvation Structures for Synergistic Solar‑Thermal Desalination of Seawater and Catalytic Degradation of Organic Pollutants

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Nano-Micro Letters 2025年第2期17卷 548-565页

作者： Ming‑Yuan Yu Jing Wu Guang Yin Fan‑Zhen Jiao zhong‑Zhen Yu Jin Qu Beijing Key Laboratory of Advanced Functional Polymer Composites Beijing University of Chemical TechnologyBeijing 100029People’s Republic of China State Key Laboratory of Organic‑Inorganic Composites College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029People’s Republic of China

Although solar steam generation strategy is efficient in desalinating seawater,it is still challenging to achieve continuous solar-thermal desalination of seawater and catalytic degradation of organic ***,dynamic regulations of hydrogen bonding networks and solvation structures are realized by designing an asymmetric bilayer membrane consisting of a bacterial cellulose/carbon nanotube/Co_(2)(OH)_(2)CO_(3)nanorod top layer and a bacterial cellulose/Co_(2)(OH)_(2)CO_(3)nanorod(BCH)bottom ***,the hydrogen bonding networks inside the membrane can be tuned by the rich surface–OH groups of the bacterial cellulose and Co_(2)(OH)_(2)CO_(3)as well as the ions and radicals in situ generated during the catalysis ***,both SO_(4)^(2−)and HSO_(5)−can regulate the solvation structure of Na^(+)and be adsorbed more preferentially on the evaporation surface than Cl^(−),thus hindering the de-solvation of the solvated Na^(+)and subsequent nucleation/growth of ***,the heat generated by the solar-thermal energy conversion can accelerate the reaction kinetics and enhance the catalytic degradation *** work provides a flow-bed water purification system with an asymmetric solar-thermal and catalytic membrane for synergistic solar thermal desalination of seawater/brine and catalytic degradation of organic pollutants.

关键词： Solar steam generation Seawater desalination Catalytic degradation Bacterial cellulose Cobalt hydroxycarbonate nanorods

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A Novel Approach of Network Coding in Wireless Networks Overhearing

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Chinese Journal of Electronics 2018年第6期27卷 1297-1304页

作者： NING Zuoting ZHANG dafang LIU Xuchong Department of Information Technology Hunan Police Academy College of Information Science and Engineering Hunan University

Network coding is proved to improve the throughput, decrease network latency and balance the network overhead. Combined with wireless overhearing, some proposed representative schemes on network coding, such as linear network coding and Completely opportunity encoding(COPE). The former scheme is based on complicated linear operation, while the latter is implemented by the way of pairwise XOR-ing which is simple and low efficiency. In order to resolve these problems, we put forward a group-based XOR-ing network coding scheme, which has the characteristics of high efficiency and low *** results and theoretical analysis demonstrate that our scheme has higher throughput gains and lower delay than traditional schemes. In addition, our proposed scheme has the best characteristic of fairness among the state-of-the-art approaches.

关键词： Network coding Wireless network Overhearing Group-based XOR-ing

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The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

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Neural Regeneration Research 2025年第11期20卷 3233-3244页

作者： Xiaoling zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA Peter O’Donnell Jr.Brain Institute University of Texas Southwestern Medical CenterDallasTXUSA

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following *** targeting this pathway is beneficial to brain injury remains *** this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral *** inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology ***,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin *** findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

关键词： adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury

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