1.Analysis of factors influencing immune checkpoint inhibitor-related thyroid adverse reactions
Jiayu LI ; Qianqian ZHANG ; Meng HOU ; Siqi ZHANG ; Keke WANG
China Pharmacy 2025;36(3):341-345
OBJECTIVE To provide reference for rational clinical use of immune checkpoint inhibitor (ICI). METHODS Electronic medical record information of patients who received ICI treatment from January 1st 2020 to December 31st 2023 at a certain hospital was collected. Patients were divided into thyroid immune-related adverse event (irAE) group (subdivided into clinical hypothyroidism, clinical hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism subgroups) and non- thyroid irAE group based on whether they experienced immune-induced thyroid irAE. Univariate and multivariate Logistic regression analyses were employed to analyze the influencing factors of ICI-related thyroid adverse events. RESULTS A total of 382 patients who received ICI treatment were included, with 137 cases in the thyroid irAE group (accounting for 35.9%) and 245 cases in the non-thyroid irAE group (accounting for 64.1%). Multivariate Logistic regression analysis, following univariate screening, revealed that ICI combined with radiotherapy was positively associated with the occurrence of thyroid irAE [odds ratio (OR)=2.157, 95% confidence interval (CI) (1.144, 4.066), P<0.05], while lung squamous cell carcinoma was negatively associated with the occurrence of thyroid irAE [OR=0.600, 95%CI (0.369, 0.975), P<0.05]. Among various thyroid irAE, nasopharyngeal malignancy was positively associated with the occurrence of immune-related clinical hyperthyroidism [OR=4.678, 95%CI (1.149, 19.042), P<0.05]; ICI combined with radiotherapy [OR=2.622, 95%CI (1.227, 5.603), P<0.05] and lung adenocarcinoma [OR=2.013, 95%CI (1.078, 3.759), P<0.05] were positively associated with the occurrence of immune-related subclinical hyperthyroidism. Age was negatively associated with the occurrence of immune-related clinical hypothyroidism [OR=0.944, 95%CI (0.896, 0.995), P<0.05]; age [OR=0.963, 95%CI (0.932, 0.994), P<0.05] and ICI combined with chemotherapy [OR=0.332, 95%CI (0.137, 0.802), P<0.05] were negatively associated with the occurrence of immune-related subclinical hypothyroidism. CONCLUSIONS Among patients receiving ICI treatment, younger patients are more prone to thyroid irAE. Patients receiving ICI combined with chemotherapy are less likely to experience subclinical hypothyroidism, while ICI combined with radiotherapy significantly increases the risk of thyroid adverse events.
2.Apixaban for the prevention and treatment of cancer-associated venous thromboembolism:a rapid health technology assessment
Huayu WANG ; Keke SHANGGUAN ; Ying WANG ; Yankui LI
China Pharmacy 2025;36(10):1260-1265
OBJECTIVE To evaluate the efficacy, safety and cost-effectiveness of apixaban in the prevention and treatment of cancer-associated venous thromboembolism (CA-VTE), and provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed, the Cochrane Library, CNKI, Wanfang, VIP database and other websites of health technology assessment (HTA), systematic review/meta-analysis, pharmacoeconomic studies and HTA reports of apixaban in the prevention and treatment of CA-VTE were collected. After data extraction and quality evaluation, the results of the included study were analyzed descriptively. RESULTS A total of 23 literatures were included, involving 16 systematic review/meta-analysis and 7 pharmacoeconomic studies. In terms of efficacy, compared with placebo, prophylactic use of apixaban could significantly reduce the incidence of venous thromboembolism (VTE) in outpatient adult cancer patients receiving chemotherapy (P<0.05). Compared with low-molecular weight heparin (LMWH), rivaroxaban and warfarin, there were no statistically significant differences in the incidence of VTE for apixaban (P>0.05); nevertheless, apixaban was ranked as the most preferable choice. For the treatment of patients with CA-VTE, compared with warfarin, apixaban could significantly reduce the recurrence rate of VTE (P<0.05). While compared with patients treated with LMWH, rivaroxaban, edoxaban and dabigatran, there were no statistically significant differences in the recurrence rates of VTE, deep venous thrombosis and pulmonary embolism among patients using apixaban (P>0.05). In terms of safety, compared with placebo, prophylactic use of apixaban showed a higher occurrence of major bleeding in outpatient adult cancer patients receiving chemotherapy (P<0.05), while compared withpatients treated with LMWH, rivaroxaban, and warfarin, there were no statistically significant differences in the incidence of major bleeding among patients using apixaban (P>0.05); despite this, apixaban was ranked as the most favorable option. For the treatment of patients with CA-VTE, compared with dalteparin, the incidence of major bleeding and all-cause mortality of apixaban were similar (P>0.05), while the incidence of clinically relevant non-major bleeding (CRNMB) was higher (P<0.05). Compared with edoxaban, the incidence of major bleeding of apixaban was reduced significantly (P<0.05), while there was no significant difference in the incidence of CRNMB, the incidence of clinically relevant bleeding and all-cause mortality (P>0.05). Compared with rivaroxaban, warfarin and dabigatran, there were no significant differences in the incidence of major bleeding, the incidence of CRNMB, the incidence of clinically relevant bleeding and all-cause mortality (P>0.05). In terms of cost-effectiveness, the researches in China showed that apixaban was cost-effective in preventing CA-VTE; foreign studies showed that apixaban was cost-effective in preventing and treating CA-VTE. CONCLUSIONS Apixaban is effective, safe and cost- effective in the prevention and treatment of CA-VTE.
3.Drug delivery systems based on mesoporous silica nanoparticles for the management of hepatic diseases.
Boyan LIU ; Wenshi LIU ; Miao XU ; Tongyi ZHAO ; Bingxin ZHOU ; Ruilin ZHOU ; Ze ZHU ; Xuchun CHEN ; Zhiye BAO ; Keke WANG ; Heran LI
Acta Pharmaceutica Sinica B 2025;15(2):809-833
The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.
4.Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition)
Jianling FAN ; Tiejun WANG ; Pengfei YANG ; Keke DING ; Xiaoning HAO ; Sunfang JIANG ; Ankang LÜ ; Jianping LU ; Sheng RONG ; Weibin SHI ; Shengwei SUN ; Yan TAN ; Qilei TU ; Zhiping WANG ; Bing WANG ; Jianyun WANG ; Weijian WANG ; Yan WANG ; Qun XU ; Chenli ZHANG ; Fan ZHANG ; Ping ZHANG ; Yansong ZHENG ; Jieru ZHOU ; Dan CHEN ; Jiaoyang ZHENG
Chinese Journal of Clinical Medicine 2025;32(6):1097-1111
Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.
5.Inhibitory effect of safranal on proliferation,migration and phenotypic transformation of vascular smooth muscle cells of rats induced by high glucose in vitro
Yixuan GAO ; Peng WANG ; Silong ZHANG ; Ruijuan GAO ; Yingfang MA ; Keke ZHANG ; Dan FENG ; Zongqi HUANG ; Ketao MA ; Li LI ; Junqiang SI
Journal of Jilin University(Medicine Edition) 2025;51(4):948-957
Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.
6.Molecular mechanism of lenvatinib resistance in hepatocellular carcinoma
Xiaomeng YAO ; Keke SUN ; Yunkai LIN ; Hui WANG ; Liwei DONG ; Lei CHEN ; Heping HU
Journal of Clinical Hepatology 2024;40(12):2524-2530
Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However, most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis, with fewer opportunities for surgery and limited treatment options. In recent years, the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies, lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma, and it has attracted widespread attention for its powerful anti-tumor properties. However, the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib, so as to improve its efficacy.
7.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.
8.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.
9.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.
10.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.

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