1.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.
2.Comparison of the efficacy, safety, and cost-effectiveness of trastuzumab biosimilar HLX02 and the originator combined with pertuzumab and chemotherapy in the neoadjuvant treatment of patients with HER-2-positive breast cancer
Zixuan LEI ; Die SANG ; Bo LAN ; Ying FAN ; Ruigang CAI ; Yang LUO ; Qiao LI ; Jiayu WANG ; Longmei ZHAO ; Peng YUAN
Chinese Journal of Oncology 2025;47(6):517-524
Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P<0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P>0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P<0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P<0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.
3.Influencing factors for kinesiophobia among elderly patients with chronic obstructive pulmonary disease
HE Huan ; ZHAO Xue ; CAI Peng ; ZHAN Xiaoya ; MA Lei
Journal of Preventive Medicine 2025;37(7):659-663
Objective:
To investigate the influencing factors for kinesiophobia among elderly patients with chronic obstructive pulmonary disease (COPD), so as to provide the reference for alleviating kinesiophobia among COPD patients.
Methods:
From December 2023 to July 2024, COPD patients aged 60 years and above who sought medical treatment at a tertiary grade-a hospital in Guiyang City were selected. Demographic information was collected through questionnaire surveys. Kinesiophobia, exercise self-efficacy, social support, type D personality and coping styles were assessed using the Chinese version of Tampa Scale for Kinesiophobia, the Chinese version of the Self-Efficacy for Exercise Scale, Social Support Rating Scale, Type D Personality Scale and Chinese version of the Medical Coping Modes Questionnaire, respectively. Factors affecting kinesiophobia among elderly patients with COPD were analyzed using a multiple linear regression model.
Results:
A total of 300 COPD patients were surveyed, including 238 males (79.33%) and 62 females (20.67%). The majority of patients had a disease duration of less than 5 years, with 130 cases (43.33%). The average kinesiophobia score was (48.01±7.74) points. The average exercise self-efficacy score was (3.39±1.01) points. The average social support score was (34.42±6.76) points. There were 280 patients (93.33%) with type D personality. The average scores of the confrontation, avoidance, and resignation dimensions of coping styles were (17.42±5.00), (13.76±1.91), and (11.81±2.95) points, respectively. Multiple linear regression analysis showed that age (70-<80 years, β'=0.124; ≥80 years, β'=0.205), educational level (primary school and below, β'=0.228; junior high school, β'=0.182), household monthly income per capita (<3 000 yuan, β'=0.234; 3 000~<5 000 yuan, β'=0.165), social support (β'=0.294), type D personality (β'= 0.170), and coping styles (confrontation dimension, β'=-0.140; avoidance dimension, β'=0.154; resignation dimension, β'=0.175) statistically associated with kinesiophobia among elderly patients with COPD.
Conclusion
Kinesiophobia among elderly patients with COPD is associated with age, educational level, household monthly income per capita, social support, type D personality and coping styles.
4.Review of chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex and prediction of its Q-markers.
Meng-Fan PENG ; Bao-Song LIU ; Pei-Pei YAN ; Cai-Xia LI ; Xiao-Fang ZHANG ; Yi ZHENG ; Ya-Gang SONG ; Tong LIU ; Lei YANG ; Ming-San MIAO
China Journal of Chinese Materia Medica 2025;50(4):946-958
Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry*
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Drugs, Chinese Herbal/pharmacology*
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Quality Control
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Humans
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Animals
5.Summary of the Evidence for Ambulatory Blood Pressure Monitoring in Adults
Xiaoya ZHAN ; Xue ZHAO ; Peng CAI ; Lei MA ; Huan HE
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1301-1308
Objective To retrieve,evaluate,and integrate evidence related to the operational proce-dures of ambulatory blood pressure monitoring(ABPM)in adults,aiming to enhance the accuracy and effec-tiveness of ambulatory blood pressure monitoring.Methods A systematic search was conducted following the"6S"pyramid model of evidence-based resources to identify literature pertaining to ABPM operations in adults from relevant domestic and international databases and websites,with the search period spanning from the inception of each database to April 2024.After screening the literature,the methodological quality of the included studies was evaluated.Evidence was extracted and summarized according to thematic categories.Results Based on the inclusion and exclusion criteria,15 publications were ultimately included,comprising 1 clinical decision,10 guidelines,1 best practice summary,and 3 expert consensus documents.A total of 32 evidence items were synthesized.Conclusions This study consolidates evidence related to ABPM operational procedures,providing an evidence-based foundation for standardizing ABPM practices among healthcare pro-fessionals.
6.Determination of Organic Fluorinated Amines in Oral Care Products by Ultra Performance Liquid Chromatography-Charged Aerosol Detector Coupled with Solid-Phase Extraction
Xiao-Fang LI ; Yan PENG ; Di XIN ; Wei ZHOU ; Xiao-Hong QIAO ; Hua-Jin SHI ; Lei ZHANG ; Guo-Qiang CAI ; Ying LIU
Chinese Journal of Analytical Chemistry 2025;53(8):1362-1370,中插100-中插105
The major components of Olaflur raw material were characterized using ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry(UPLC-Q-TOF/MS).The results revealed that cetyl amine fluoride(C16-AmF),octadecene amine fluoride(C18:1-AmF),and octadecyl amine fluoride(Olaflur)were the main components.The contents of C16-AmF,C18:1-AmF,and Olaflur in oral care products were determined via ultra performance liquid chromatography-charged aerosol detector coupled with solid-phase extraction(SPE-UPLC-CAD).The oral care sample was dispersed evenly with a 50%ethanol aqueous solution,and then vortexed with ethanol.The supernatant was collected by centrifugation,concentrated to near dryness,and redissolved with ultrapure water.The re-dissolved sample was loaded onto a Poly-Sery HLB Pro SPE column for purification and elution.The acetonitrile eluate was collected and concentrated to 1.0 mL.Finally,a prepared test solution was separated on a Thermo Acclaim Surfactant Plus chromatographic column(2.1 mm×150 mm,3 μm).Acetonitrile and 100 mmol/L acetic acid-ammonium acetate aqueous solution(pH=4.8)were used as the mobile phases for gradient elution.The flow rate was 0.3 mL/min and cloumn temperature was maintained at 40℃.The sample was detected using a charged aerosol detector,and quantified using an external standard method.The experimental results indicated that the three organic fluorinated amines showed good linear relationship in their respective concentration ranges.The correlation coefficients(r)were greater than 0.99.The limit of detection(LOD)and the limit of quantification(LOQ)of C16-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of C18:1-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of Olaflur were 3.0 μg/mL and 10.0 μg/mL,respectively.The spiked recoveries of the three organic fluorinated amines were 84.3%-104.2%,with relative standard deviations(RSDs)of 4.93%-5.82%.The 28 batches of commercial oral care samples were detected by this method and the results indicated that three organic fluorinated amines were detected in 18 samples and the total content were 22.2-11477.8 μg/g.This method had high sensitivity and good reproducibility.It was suitable for verifying the authenticity of the claims of oral care products promoted with Olaflur as the main efficacy ingredient and selling point,and provided a valuable reference for establishing and improving the standard analytical method for Olaflur.
7.Determination of genotoxic impurities in tosufloxacin tosylate hydrate by GC-MS-MS
Hongyu CHEN ; Xueqing CHENG ; Lirong CAI ; Yanming LIU ; Jinfeng ZHENG ; Feicheng PENG ; Lei FAN
Drug Standards of China 2025;26(4):393-398
Objective:To establish a gas chromatography-mass spectrometry method(GC-MS-MS)for determining the content of methyl p-toluenesulfonate(MTS),ethyl p-toluenesulfonate(ETS),and isopropyl p-toluenesulfonate(IPTS)in tosufloxacin tosylate hydrate.Methods:The HP-1MS(0.250 mm ×30 m,0.50 μm)column was used at progamming temperature,the injection temperature was 250 ℃.The MS conditions were as follow:the ionization mode was EI,the electron voltage was 70 V,the ion source temperature was 250 ℃,the scanning method was MRM,the quantitative ion pairs for MTS,ETS and IPTS were m/z 91 →65,m/z 155→91 and m/z 91→65.Results:The linearity ranges of MTS,ETS and IPTS were 48.779-975.59 ng·mL-1(r=0.998 5),54.586-1 091.7 ng·mL-1(r=0.998 4)and 46.241-924.82 ng·mL-1(r=0.999 8).The average recoveries were 99.47%,99.15%,98.83%(n=9).The MTS,ETS and IPTS were not detected in the 7 batches of tosufloxacin tosylate hydrate.Conclusion:The established method can be used for the determination of MTS,ETS,and IPTS content in tosufloxacin tosylate hydrate.
8.Chinese experts' consensus on principles of preoperative hair removal
Yiping MAO ; Jun ZHENG ; Lei LI ; Deyan YANG ; Bing ZHANG ; Lei YANG ; Wang JIA ; Peng KANG ; Hui JIAO ; Yun YANG ; Qi QI ; Shiqing FENG ; Xiao LONG ; Yuewei ZHANG ; Xiaohui WANG ; Lize WANG ; Yuan WEI ; Jichao ZHOU ; Minghui MAO ; Pengju XIN ; Hongyu TAN ; Dahong ZHANG ; Lianxin LIU ; Lei TAO ; Xietong WANG ; Xiaoning YUAN ; Mang CAI ; Li MU ; Fang DU ; Rongzhu CHEN ; Fengmao ZHAO ; Jiuzuo HUANG ; Mingzi ZHANG ; Jie ZHANG ; Baoguo WANG ; Kun WANG ; Fang LUO ; Jinhua ZHANG ; Nong HE ; Ling LYU ; Zhiyong ZONG
Chinese Journal of Nosocomiology 2025;35(10):1441-1449
To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.
9.Determination of genotoxic impurities in tosufloxacin tosylate hydrate by GC-MS-MS
Hongyu CHEN ; Xueqing CHENG ; Lirong CAI ; Yanming LIU ; Jinfeng ZHENG ; Feicheng PENG ; Lei FAN
Drug Standards of China 2025;26(4):393-398
Objective:To establish a gas chromatography-mass spectrometry method(GC-MS-MS)for determining the content of methyl p-toluenesulfonate(MTS),ethyl p-toluenesulfonate(ETS),and isopropyl p-toluenesulfonate(IPTS)in tosufloxacin tosylate hydrate.Methods:The HP-1MS(0.250 mm ×30 m,0.50 μm)column was used at progamming temperature,the injection temperature was 250 ℃.The MS conditions were as follow:the ionization mode was EI,the electron voltage was 70 V,the ion source temperature was 250 ℃,the scanning method was MRM,the quantitative ion pairs for MTS,ETS and IPTS were m/z 91 →65,m/z 155→91 and m/z 91→65.Results:The linearity ranges of MTS,ETS and IPTS were 48.779-975.59 ng·mL-1(r=0.998 5),54.586-1 091.7 ng·mL-1(r=0.998 4)and 46.241-924.82 ng·mL-1(r=0.999 8).The average recoveries were 99.47%,99.15%,98.83%(n=9).The MTS,ETS and IPTS were not detected in the 7 batches of tosufloxacin tosylate hydrate.Conclusion:The established method can be used for the determination of MTS,ETS,and IPTS content in tosufloxacin tosylate hydrate.
10.Chinese experts' consensus on principles of preoperative hair removal
Yiping MAO ; Jun ZHENG ; Lei LI ; Deyan YANG ; Bing ZHANG ; Lei YANG ; Wang JIA ; Peng KANG ; Hui JIAO ; Yun YANG ; Qi QI ; Shiqing FENG ; Xiao LONG ; Yuewei ZHANG ; Xiaohui WANG ; Lize WANG ; Yuan WEI ; Jichao ZHOU ; Minghui MAO ; Pengju XIN ; Hongyu TAN ; Dahong ZHANG ; Lianxin LIU ; Lei TAO ; Xietong WANG ; Xiaoning YUAN ; Mang CAI ; Li MU ; Fang DU ; Rongzhu CHEN ; Fengmao ZHAO ; Jiuzuo HUANG ; Mingzi ZHANG ; Jie ZHANG ; Baoguo WANG ; Kun WANG ; Fang LUO ; Jinhua ZHANG ; Nong HE ; Ling LYU ; Zhiyong ZONG
Chinese Journal of Nosocomiology 2025;35(10):1441-1449
To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.


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