1.Overview of the amendments and revisions to the General Technical Requirements adopted by the Volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition
ZHANG Jun ; NING Baoming ; WEI Shifeng ; SHEN Haoyu ; SHANG Yue ; ZHU Ran ; XU Xinyi ; CHEN Lei ; LIU Tingting ; MA Shuangcheng
Drug Standards of China 2025;26(1):034-044
To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines; further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly; replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.
2.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.
3.Discussion on the medication law of Wang Xugao for the treatment of phlegm-drinking disease based on data mining
Baixiao CHEN ; Ying ZHONG ; Canmei LI ; Yangling HUANG ; Shifeng LIN ; Yaping ZHANG
International Journal of Traditional Chinese Medicine 2024;46(1):97-102
Objective:To explore the prescription ideas of treating phlegm-drinking disease in Wang Xugao Lin Zheng Yi An; To analyze the medication law of Wang Xugao's clinical treatment of phlegm-drinking disease. Methods:The database was established based on the medical records of the chapter of phlegm, fluid retention and liver wind and phlegm fire contained in Wang Xugao Lin Zheng Yi An. Excel 2017 software was used to analyze the frequency, taste and meridian tropism of all Chinese materia medica. For Chinese materia medica with frequency≥10, IBM SPSS Modeler 18 software was used to analyze the association rules based on Apriori algorithm, and SPSS 25.0 software was used for cluster analysis based on Ochiai algorithm. Results:A total of 80 medical cases were included, involving 114 prescriptions, including 191 flavors of Chinese materia medica . High-frequency Chinese materia medica mainly included Poria, Pinelliae Rhizoma, Citri Reticulatae Pericarpium, Atractylodis Macrocephalae Rhizoma and Armeniacae Semen Amarum, etc. The main properties in Wang Xugao's medication for the treatment of phlegm-drink disease were warm, followed by cold and mild. The main tastes were sweet, bitter and pungent. Drugs mainly belong to the lung meridian and spleen, stomach, liver, kidney meridians; several core medicinal pairs were obtained, such as Farfarae Flos - Armeniacae Semen Amarum, Pinelliae Rhizoma - Zingiberis Rhizoma, Uncariae Ramulus cum Uncis - Haliotidis Concha, etc. Eight groups of core drug combinations could be sorted out by clustering analysis.Conclusions:In the treatment of phlegm-drinking disease, Wang Xugao paid attention to the simultaneous treatment of multiple viscera to coordinate the balance between the viscera, emphasized the complex etiology of phlegm-drinking disease combined with cold, fire and dampness, attached importance to the treatment of healthy qi to retreat pathogens, the regulation of three-energizer to regulate qi flow. The treatment of three-energizer, promoting yang and reducing phlegm, clearing liver and dispelling wind are the main methods. Medication mainly chooses properties of sweet and warm, with bitter and pungent.
4.Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation
Yao MA ; Yanfang ZHANG ; Kang ZHOU ; Yun LUO ; Shu CHEN ; Shifeng LOU ; Jianchuan DENG
Journal of Army Medical University 2024;46(4):319-325
Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4%)patients were DSA positive,including 7(46.7%)cases of strong positive,3(20.0%)cases of moderate positive,and 5(33.3%)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95%CI:1.505~57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100%rate of successful transplantation,and 6 received single desensitization,with 4(66.7%)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.
5.Correlation analysis of sleep quality and cognitive function in elderly patients with sleep disorders
Journal of Public Health and Preventive Medicine 2024;35(4):149-152
Objective To explore the correlation between sleep quality and cognitive function in elderly patients with sleep disorders. Methods A retrospective analysis was performed on 145 elderly patients with sleep disorders (elderly sleep disorder group) and 111 elderly subjects without sleep disorders (non-sleep disorder group). The general data, scores and positive rates of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were compared between the two groups. The correlation between sleep disorder and cognitive function was analyzed by Pearman correlation coefficient, and binary Logistic regression analysis was established to analyze whether sleep disorder was an independent risk factor affecting the cognitive dysfunction of elderly patients. Results The scores of MMSE scale and MoCA scale in elderly sleep disorder group were significantly lower than those in non-sleep disorder group (P<0.05), and the positive rates of MMSE and MoCA were significantly higher than those in non-sleep disorder group (P<0.05). According to Pearman correlation coefficient analysis, sleep disorder in elderly patients was negatively correlated with positive MMSE and positive MoCA (r=-0.658, -0.712, P<0.001). Binary Logistic regression analysis showed that sleep disorder was an independent risk factor affecting the cognitive function of elderly patients (P<0.05). Conclusion Sleep disorder in elderly patients has a certain correlation with cognitive function, and it is an independent risk factor affecting the cognitive function in elderly patients.
6.Biomechanical characteristics of thoracic T10 bone tumor metastasis at different locations:three-dimensional finite element analysis
Guoren XIA ; Hao YU ; Shifeng JIANG ; Xin PENG ; Xiao FU ; Qi CHEN ; Lizhuang YANG ; Tengfei WANG ; Hai LI
Chinese Journal of Tissue Engineering Research 2024;28(36):5759-5765
BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.
7.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
8.Value of APTw imaging combined with DCE-MRI quantitative parameters for preoperative assessment of Her-2 gene expression in endometrial cancer
Changjun MA ; Shifeng TIAN ; Qingling SONG ; Lihua CHEN ; Nan WANG ; Qingwei SONG ; Ailian LIU
Chinese Journal of Radiology 2024;58(6):620-626
Objective:To investigate the value of quantitative parameters of amide proton transfer-weighted (APTw) imaging and dynamic contrast-enhanced (DCE)-MRI for preoperative assessment of human epidermal growth factor receptor 2 (Her-2) gene expression in endometrial cancer (EC).Methods:This research conducted a diagnostic pilot study involving 68 patients with pathologically confirmed EC at the First Hospital of Dalian Medical University from August 2019 to August 2023. Patients were categorized into Her-2-positive group (33 cases) and Her-2-negative group (35 cases) based on postoperative Her-2 gene expression results. Utilizing the APTw and DCE-MRI sequences, quantitative parameters including the asymmetric magnetization transfer ratio (MTR asym) for APTw and the volumetric transfer constant (K trans), plasma volume fraction (V p), extracellular mesenchymal space (V e), and rate constant (K ep) for DCE-MRI were acquired for the lesion site. Statistical differences in the values of each quantitative parameter between the two groups were evaluated using two independent sample t test or Mann-Whitney U test. The study incorporated quantitative parameters and clinicopathological data of patients to identify independent predictors of EC Her-2 gene expression through logistic regression analysis. A diagnostic model was developed using binary logistic regression analysis. The effectiveness of the parameters and diagnostic model was evaluated using receiver operating characteristic curves. DeLong test was used to compare the differences between the areas under the curves (AUC). Results:The study found statistically significant differences in MTR asym, K trans, and V e between the Her-2-positive group and the Her-2-negative group ( Z=2.55, P=0.011; t=-2.03, P=0.047; t=-2.13, P=0.037). However, the differences in V p and K ep were not statistically significant ( Z=0.58, P=0.560; Z=0.19, P=0.849). MTR asym emerged as a significant independent predictor of Her-2 gene expression in EC ( OR=1.016, 95% CI 1.003-1.030, P=0.014). Incorporating MTR asym, K trans, and V e, the diagnostic model yielded an AUC (95% CI) of 0.745 (0.625-0.864). The AUC (95% CI) for MTR asym, K trans, and V e alone were 0.680 (0.551-0.808), 0.623 (0.485-0.760), and 0.656 (0.523-0.789) respectively. The differences in AUC between the diagnostic model and individual predictors MTR asym, K trans, and V e were not found to be statistically significant ( Z=1.40, 1.92, 1.37, P=0.163, 0.055, 0.171). Conclusion:The quantitative parameters of APTw and DCE-MRI sequences can preoperatively assess EC Her-2 gene expression from a different perspective, with MTR asym potentially serving as a valuable independent predictor.
9.The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.
Yixiu ZHAO ; Zhiqi WANG ; Jing REN ; Huan CHEN ; Jia ZHU ; Yue ZHANG ; Jiangfei ZHENG ; Shifeng CAO ; Yanxi LI ; Xue LIU ; Na AN ; Tao BAN ; Baofeng YANG ; Yan ZHANG
Frontiers of Medicine 2024;18(6):1068-1086
Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals
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Atherosclerosis/prevention & control*
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Mice
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Receptor, Fibroblast Growth Factor, Type 1/metabolism*
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Signal Transduction/drug effects*
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Anthraquinones/pharmacology*
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Humans
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Integrin beta1/metabolism*
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Epithelial-Mesenchymal Transition/drug effects*
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Male
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Transforming Growth Factor beta/metabolism*
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Disease Models, Animal
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Mice, Inbred C57BL
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Human Umbilical Vein Endothelial Cells/drug effects*
10.Curcumin in Treatment of Osteosarcoma: A Review
Fei TENG ; Chongxiao SUN ; Yi CHEN ; Ao YANG ; Shifeng ZHANG ; Bin GENG ; Yayi XIA
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):275-282
Osteosarcoma (OS) is the most common primary malignant bone tumor originating from mesenchymal stem cells, which features high degree of malignancy, strong invasiveness, easy early metastasis, and high recurrence rate. The clinical manifestations of OS are pain, local mass, limited movement, and pathological fracture. OS mainly occurs in children, adolescents, and the elderly, seriously threatening physical and mental health of patients, as well as their quality of life. The currently available therapies for OS are surgery, chemoradiotherapy, and the combination of the two. Although the therapeutic effect has been improved, tumor recurrence and metastasis and multidrug resistance still occur. Thus, the therapeutic effect is not satisfactory, especially in improving the overall survival rate of patients with metastatic OS. As a result, clinicians and researchers have been making efforts to find an effective therapy. In recent years, the mechanism of curcumin (CUR) against OS has attracted wide attention. CUR, a pigment extracted from the rhizomes or tubers of many plants, such as Curcuma longa, C. rcenyujin, and C. phaeocaulis, has a variety of pharmacological effects. Scholars have found that CUR has the effects of inhibiting proliferation, inducing apoptosis, and reversing multidrug resistance (MDR) of tumor cells, but also it has poor water solubility and low bioavailability, which limit the clinical application. This paper mainly discusses the mechanism of CUR against OS, the existing problems, new treatment methods, and future research directions, which is expected to provide new ideas for scientific researchers and provide a reference for the development and utilization of CUR in the future.


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