1.Expression and functional study of FKBP10 in oral squamous cell carcinoma
FANG Zhikai ; JIN Hui ; YANG Shan ; JIANG Nan ; ZHANG Mingyu ; ZHOU Shuang ; LI Chang ; LI Lili
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):529-541
Objective:
To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC.
Methods:
A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot.
Results:
According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05).
Conclusion
FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.
2.Guiqi Yiyuan Ointment combined with cisplatin inhibits tumor growth in Lewis lung carcinoma-bearing mice by regulating PERK/eIF2α/ATF4/CHOP signaling pathway.
Nan YANG ; Jian-Qing LIANG ; Ke-Jun MIAO ; Qiang-Ping MA ; Jin-Tian LI ; Juan LI
China Journal of Chinese Materia Medica 2025;50(6):1592-1600
This study aims to investigate the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung carcinoma-bearing mice via the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α(eIF2α)/activated transcription factor 4(ATF4)/C/EBP homologous protein(CHOP) signaling pathway. Sixty SPF-grade male C57BL/6 mice were selected and assigned into a blank group and a modeling group by the random number table method. After modeling of the Lewis lung carcinoma, the mice in the modeling group were randomized into model, cisplatin(5 mg·kg~(-1), once a week), and low-, medium-, and high-dose(1.7, 3.5, and 7.05 g·kg~(-1), respectively, once a day) Guiqi Yiyuan Ointment+cisplatin(5 mg·kg~(-1)) groups(n=10). After 14 days of continuous intervention, the spleen, thymus, and tumor samples of the mice were collected, weighed, and recorded, and the spleen index, thymus index, and tumor suppression rate were calculated. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the tumor tissue. The morphological changes of the endoplasmic reticulum of tumor cells were observed by transmission electron microscopy. The positive expression of phosphorylated eIF2α(p-eIF2α) and ATF4 in the tumor tissue was detected by immunofluorescence. Western blot was employed to determine the protein levels of phosphorylated PERK(p-PERK), p-eIF2α, ATF4, CHOP, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinase inhibitor 1A(p21), and cyclinD1 in the tumor tissue. Real-time fluorescent quantitative PCR was employed to determine the mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, p21, and cyclinD1 in the tumor tissue. Compared with the blank group, the model group showed decreases in spleen index and thymus index(P<0.05). Compared with the model group, the cisplatin group showed decreases in spleen index and thymus index(P<0.05), and the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups presented increases in spleen index and thymus index(P<0.05). In addition, the treatment groups all showed decreased tumor mass(P<0.05), increased tumor cell lysis and nuclear rupture, widened gap between rough endoplasmic reticulum, enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). Compared with the cisplatin group, the combination groups showed increases in spleen index and thymus index(P<0.05) as well as mean optical density(P<0.05), and the high-dose Guiqi Yiyuan Ointment+cisplatin group showed decreased tumor mass(P<0.05). In addition, the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups showcased enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). In conclusion, Guiqi Yiyuan Ointment combined with cisplatin can effectively inhibit the growth of Lewis lung carcinoma in mice by regulating the expression of proteins related to the PERK/eIF2α/ATF4/CHOP signaling pathway and promoting cell cycle arrest and apoptosis.
Animals
;
Cisplatin/administration & dosage*
;
Activating Transcription Factor 4/genetics*
;
Eukaryotic Initiation Factor-2/genetics*
;
eIF-2 Kinase/genetics*
;
Carcinoma, Lewis Lung/pathology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Mice
;
Signal Transduction/drug effects*
;
Mice, Inbred C57BL
;
Transcription Factor CHOP/genetics*
;
Ointments/administration & dosage*
;
Humans
;
Cell Proliferation/drug effects*
;
Antineoplastic Agents/administration & dosage*
3.Optimization of extraction process for Shenxiong Huanglian Jiedu Granules based on AHP-CRITIC hybrid weighting method, grey correlation analysis, and BP-ANN.
Zi-An LI ; De-Wen LIU ; Xin-Jian LI ; Bing-Yu WU ; Qun LAN ; Meng-Jia GUO ; Jia-Hui SUN ; Nan-Yang LIU ; Hui PEI ; Hao LI ; Hong YI ; Jin-Yu WANG ; Liang-Mian CHEN
China Journal of Chinese Materia Medica 2025;50(10):2674-2683
By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis*
;
Neural Networks, Computer
4.Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion".
Ming-Yi ZHAO ; Rong HUANG ; Rong GUI ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):18-25
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans
;
Child
;
Hematologic Diseases/therapy*
;
Blood Transfusion/standards*
;
Practice Guidelines as Topic
5.Explanation and interpretation of the compilation of blood transfusion provisions for children undergoing hematopoietic stem cell transplantation in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(2):139-143
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans
;
Hematopoietic Stem Cell Transplantation
;
Child
;
Blood Transfusion/standards*
;
Practice Guidelines as Topic
6.Explanation and interpretation of blood transfusion provisions for critically ill and severely bleeding pediatric patients in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI
Chinese Journal of Contemporary Pediatrics 2025;27(4):395-403
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Critically ill children often present with anemia and have a higher demand for transfusions compared to other pediatric patients. This guideline provides guidance and recommendations for blood transfusions in cases of general critical illness, septic shock, acute brain injury, extracorporeal membrane oxygenation, non-life-threatening bleeding, and hemorrhagic shock. This article interprets the background and evidence of the blood transfusion provisions for critically ill and severely bleeding children in the "Guideline for pediatric transfusion", aiming to enhance understanding and implementation of this aspect of the guidelines. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(4): 395-403.
Humans
;
Critical Illness
;
Blood Transfusion/standards*
;
Child
;
Hemorrhage/therapy*
;
Practice Guidelines as Topic
7.Explanation and interpretation of blood transfusion provisions for children undergoing cardiac surgery in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Jin-Ping LIU
Chinese Journal of Contemporary Pediatrics 2025;27(7):778-785
To guide clinical blood transfusion practices in pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Children undergoing cardiac surgery are at high risk of bleeding, and the causes of perioperative anemia and coagulation disorders in neonates and children are complex and varied, often necessitating the transfusion of allogeneic blood components. This guideline provides direction and recommendations for specific measures in blood management for children undergoing cardiac surgery before, during, and after surgery. This article interprets the background and evidence for the formulation of the blood transfusion provisions for children undergoing cardiac surgery, hoping to facilitate the understanding and implementation of this guideline.
Humans
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Cardiac Surgical Procedures
;
Blood Transfusion/standards*
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Child
;
Practice Guidelines as Topic
8.Prognostic Significance of Endothelial Activation and Stress Index in Mantle Cell Lymphoma.
Xin-Yue ZHOU ; Zhi-Qin YANG ; Jin HU ; Feng-Yi LU ; Qian-Nan HAN ; Huan-Huan ZHAO ; Wen-Xia GAO ; Yu-Han MA ; Hu-Jun LI ; Zhen-Yu LI ; Kai-Lin XU ; Wei CHEN
Journal of Experimental Hematology 2025;33(4):1051-1056
OBJECTIVE:
To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL).
METHODS:
A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment.
RESULTS:
A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.
CONCLUSION
At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans
;
Lymphoma, Mantle-Cell/pathology*
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Prognosis
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
Aged
;
ROC Curve
9.Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.
Xiao-Nan ZHANG ; Yan-Yang LI ; Shi-Chao LYU ; Qiu-Jin JIA ; Jun-Ping ZHANG ; Long-Tao LIU
Chinese journal of integrative medicine 2025;31(3):240-250
OBJECTIVE:
To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.
METHODS:
A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively.
RESULTS:
The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis.
CONCLUSIONS
SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals
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Myocytes, Cardiac/metabolism*
;
Apoptosis/drug effects*
;
MicroRNAs/genetics*
;
Rats, Sprague-Dawley
;
Male
;
Drugs, Chinese Herbal/administration & dosage*
;
Doxorubicin/pharmacology*
;
Proto-Oncogene Proteins c-bcl-2/genetics*
;
Drug Combinations
;
Injections
;
Rats
10.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.


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