1.Advances in immunosuppressive receptor LILRB4 in tumors and inflammatory diseases
Jingyi CHEN ; Yiliu LIU ; RUKEYA·Tu'erxunjiang ; Rui DING ; Jinping YIN ; Zuowen LIANG ; Jia ZHAO ; Jing LI
Chinese Journal of Immunology 2024;40(7):1559-1564
The leukocyte immunoglobulin-like receptor LILRB4(ILT3 or CD85k),a member of the immunosuppressive re-ceptor family,is expressed predominantly on the cell membranes of immune cells of myeloid origin,and exerts an immunosuppressive effect in immune regulation by activating either the autoinhibitory motif(ITIM)or by inhibiting Fc receptor activation motif(ITAM).In tumors,activation of LILRB4 receptor generates an immunosuppressive tumor microenvironment that assists in tumor invasion and metastasis,and in inflammatory diseases,LILRB4 is expressed on a variety of cells,such as monocytes,macrophages,mast cells,etc.,and attenuates inflammatory responses.Currently,LILRB4 has become a therapeutic target for tumors and various inflammatory diseases,and anti-LILRB4 monoclonal antibodies against acute myeloid leukemia(AML)have entered clinical trials.This review dis-cusses LILRB4 in terms of its structural distribution,signaling,therapeutic targets,and new drug development.
2.Hotspots and frontiers of human resource allocation research in public hospitals:a CiteSpace-based analysis of domestic and international studies
Ling YIN ; Tong ZHAO ; Jinping DI ; Fangjie WANG ; Haixiang SUN ; Qing ZHANG ; Xue ZHENG ; Wei CAO
Modern Hospital 2024;24(3):340-347,350
Objective To investigate the current status,evolving hotspots,and emerging trends in the field of human re-source allocation research in public hospitals,both domestically and internationally,to provide a reference for future research di-rections in China.Methods CiteSpace was used to conduct a visual analysis of the research literature on human resource alloca-tion in public hospitals based on China National Knowledge Infrastructure(CNKI)and the Web of Science(WOS).The analysis encompassed co-authorship,institutional collaboration,keyword co-occurrence and clustering,and burst detection.Results A total of 1 417 Chinese articles and 981 international articles were included.Domestic research in this field focused more on healthcare reform and management,resource allocation,hierarchical diagnosis,and treatment,and informatization and efficiency improvement.On the contrary,international research primarily centered on the employee satisfaction,healthcare system quality,work environment and medical staff.Future trends in domestic research included cost reduction,efficiency enhancement,and a greater emphasis on public welfare in public hospitals,while international research was beginning to explore the influence of polit-ical concepts in this field.Conclusion Compared to international research,domestic research needs to further improve its theo-retical and localized understanding,broaden its research scope,explore the interdisciplinary collaboration opportunities,and delve into research directions such as the application of artificial intelligence and automation technology in healthcare services,management of a diverse workforce,and innovative management techniques and applications.
3.Research status of TCM human resources in China based on bibliometrics
Jiaying SUN ; Jinping LUO ; Qianwen ZHANG ; Wenqiang YIN ; Zhongming CHEN ; Qichao REN ; Dongping MA
China Pharmacy 2023;34(24):2975-2981
OBJECTIVE To understand the current status of research on traditional Chinese medicine(TCM) human resources, and to provide a reference for expanding research ideas on TCM human resources and promoting the construction of TCM talents. METHODS From January 1, 2000 to December 31, 2022, literature related to TCM human resources was collected from the three major databases of CNKI, Wanfang and VIP. Using CiteSpace 5.8 R3 software, visualization analysis was performed for the literature in terms of publication time, journal sources, authors, institutions and areas, funding, research content, keywords, etc. RESULTS A total of 324 literature related to TCM human resources in China were included, and the number of literature issued showed an upward trend, with an annual average of 14.09 literature; 161 kinds of journals were involved, core journals accounted for 18.21% of the total publication volume; a total of 23 authors had published 2 or more literature, with a total of 55 literature published (16.98%); a total of 416 institutions were involved, mainly schools (66.83%); 60.49% of the literature were supported by the fund. The majorities of 324 literature were survey studies (170 literature), and most of them used self-designed questionnaires (55 literature); the high-frequency keywords included talent training, human resources, TCM, etc. The keywords were clustered into 7 categories, such as “human resources“”talent training“”TCM industry“”TCM services“”talent training models” “fairness” and “TCM talents”. The main problems described in the literature included insufficient talent, lack of reasonable distribution of regional structure, lack of reasonable plans for talent training, and insufficient professional knowledge and abilities. Continuously cultivating high-level talents and improving employment conditions in areas with severe human resource loss were the corresponding countermeasures proposed in the literature. CONCLUSIONS The research on TCM human resources starts late but has developed rapidly overall, and the quality of research needs to be improved; the structure of research team is single and unevenly distributed geographically; there is a structural imbalance in the allocation of human resources, as well as problems such as a shortage of professional talents, low levels of education and training and incomplete development systems.
4.Correlation Between Vimentin and Hepatocellular Carcinoma and Intervention Effect of Jianpi Yiqi Prescription
Chao WANG ; Jinping YIN ; Xiao JIANG ; Shaoyuan ZHUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):123-133
ObjectiveTo study the correlation between Vimentin and hepatocellular carcinoma (HCC) and the mechanism of Jianpi Yiqi prescription against HCC through Vimentin. MethodCorrelation between Vimentin and HCC was analyzed based on the cancer genome atlas(TCGA), clinical proteomic tumor analysis consortium(CPTAC), STRING, and Cytoscape. SD rats were randomized into normal group (normal saline, ig, once/day, 4 weeks), model group (normal saline, ig, once/day, 4 weeks), low-dose, medium-dose, and high-dose (5.25, 10.5, 21 g·kg-1, ig, once/day, 4 weeks) JianpiYiqi prescription groups, signal transducer and activator of transcription 3 (STAT3) inhibition group (C188-9, 4.5 mg·kg-1, ip, once/day, 4 weeks), and glycoprotein 130 (gp130) inhibition group (SC144, 4.5 mg·kg-1, ip, once/day, 4 weeks), 10 rats in each group. Diethylnitrosamine (DEN, 70 mg·kg-1 body weight, ip) was injected in rats except the normal group to induce HCC. After the modeling, administration began. After last administration, Real-time polymerase chain reaction(Real-time PCR) was performed to determine Vimentin mRNA level in rat liver tissue. Caspase-3 activity in liver tissue was detected by colorimetry, and expression of Rho kinase (ROCK)1, ROCK2, aurora kinase B (AURKB), Zinc-finger protein 148 (ZNF148)/zinc-binding protein-89 (ZBP-89), STAT3, p-STAT3, total Vimentin, and phosphorylated (p)-Vimentin in liver tissue and Vimentin in liver tissue nucleus detected by Western blot. Serum Vimentin concentration was measured by enzyme-linked immunosorbent assay (ELISA). ResultVimentin mRNA level was high in tissues from HCC patients with different cancer stages (stage Ⅰ-Ⅳ), different pathological grades (G1-G3), no regional lymph node metastasis (N0), and different subtypes (P<0.01). Vimentin mRNA expression was higher in tissues from patients with lymph node metastasis than in patients without lymph node metastasis and normal samples. Vimentin protein level was decreased in HCC tissues (P<0.01). Vimentin gene has 4 mutations which can induce change in the primary structure of Vimentin protein and patients with Vimentin gene mutation had short disease free survival time (P<0.01). The mRNA expression of Vimentin was negatively associated with HCC cell purity (P<0.01) but was positively associated with the infiltration levels of cancer-associated fibroblasts, M2 macrophages, myeloid dendritic cell and other immune cells in tumor microenvironment (P<0.01). Association analysis results showed that the expression of Vimentin was correlated with the STAT3 expression in HCC tissues (P<0.01). As for the animal experiment, Vimentin mRNA level and protein levels of total Vimentin and p-Vimentin in liver tssue, Vimentin protein level in liver tissue nucleus, Vimentin in rat serum, ROCK2, AURKB, STAT3 and p-STAT3 in liver tissues were up-regulated (P<0.01) and protein level of negative regulator ZBP-89 was reduced in the model group (P<0.01) compared with those in the normal group. Activity of Caspase-3 in liver tissue increased and the ROCK1 protein level was increased in the model group compared with those in the normal group. STAT3 inhibitor, gp130 inhibitor, and medium-dose and high-dose Jianpi Yiqi prescription all can reduce the secretory Vimentin protein in serum, protein levels of total Vimentin and p-Vimentin in liver tissues, and Vimentin in liver tissue nucleus, and the protein levels of STAT3/Vimentin signaling pathway-related molecules, such as STAT3, p-STAT3, ROCK2, and AURKB and up-regulate the protein level of negative regulator ZBP-89 and activity of Caspase-3 (P<0.05, P<0.01). Effect of medium-dose or high-dose Jianpi Yiqi prescription on Vimentin mRNA expression, STAT3 protein expression, ZBP-89 protein expression, ROCK2 protein expression, AURKB protein expression and Caspase-3 activity was not significantly different from that of STAT3 inhibitor. ConclusionVimentin, an important inflammatory molecule, is closely related to the occurrence and development of HCC and its expression, subcellular location and function may be affected by cancer-associated fibroblasts, M2 macrophages, myeloid dendritic cell, and IL-6/STAT3 signaling pathway, particularly by STAT3 molecule. Jianpi Yiqi prescription may exert therapeutic effect on HCC via regulating Vimentin through the STAT3/Vimentin signaling pathway.
5.Application of pre-operative color Doppler-guided analysis of vascular distribution in syndactyly
Jinping WANG ; Fei YIN ; Ximing WANG ; Jun GU ; Hai HUANG
Chinese Journal of Plastic Surgery 2023;39(12):1331-1336
Objective:To analyze the vascular distribution of palmar digital arteries in syndactyly through color Doppler ultrasound angiography and make the classification according to the level of artery bifurcation points, discusse its clinical significance.Methods:A retrospective analysis was performed for the data of children with congenital and digital malformations admitted to Wuxi Ninth People’s Hospital from January 2017 to December 2022. Preoperative vascular ultrasonography of the hand was performed to locate the bifurcation point of the common palmar digital artery in the digital webbed area. The vascular conditions were classified according to the distance between the bifurcation point and the 1/3 point of the proximal phalangeal as the reference, such as normal type (<0 mm), mild reduction type (0-5 mm), moderate decrease type (6-10 mm), and severe reduction type (>10 mm), absent type (only 1 artery between the fingers). The total variation of the bifurcation point of the common palmar digital artery in the children, as well as the proportion of different vascular condition subtypes were recorded. According to the classification of blood vessels, the corresponding operation plan was made. The positioning accuracy of color Doppler ultrasound angiography was evaluated based on the gold standard of common palmar digital artery bifurcation points detected during operation. Complications such as postoperative infection, flap necrosis, finger vasospasm and the morphology of finger web at the last follow-up were observed. Descriptive statistical analysis was used.Results:A total of 123 children with 181 finger webs were enrolled, including 72 males and 51 females, aged 10-28 months. There were 55 cases of simple type, 36 cases of complex type (bone) and 32 cases of Poland syndrome. Color Doppler ultrasound angiography showed that the total variation rate of the common palmar digital arterial bifurcation point was 24.3% (44/181), of which 11.6% (21/181) were mildly reduced type, 8.3% (15/181) were moderately reduced type, 3.3% (6/181) were severe reduced type, and 1.1% (2/181) were absent type. The vascular variation rates of simple syndactyly, bony syndactyly, and Poland syndrome were 0 (0/55), 19.5% (7/36), and 41.1% (37/90), respectively. Compared with the actual situation during surgery, the positioning accuracy of color Doppler ultrasound angiography was 100%. All pediatric surgeries were successfully completed, and the flaps and skin grafts survived smoothly. There were no postoperative complications such as infection, vascular crisis, or finger necrosis. All patients were followed up for 6 to 27 months, with an average of 13.5 months. At the last follow-up, the depth, width, and slope of the fingerwebs were all close to normal.Conclusion:Congenital syndactyly has a high variation rate at the bifurcation point of the common palmar digital artery, and bony syndactyly and Poland syndrome refer to the need to improve preoperative vascular evaluation. Color Doppler ultrasound angiography has the advantages of no radiation, high sensitivity and low price, and the vascular typing based on color Doppler can improve the reliable basis for the formulation of clinical surgical plans.
6.Application of pre-operative color Doppler-guided analysis of vascular distribution in syndactyly
Jinping WANG ; Fei YIN ; Ximing WANG ; Jun GU ; Hai HUANG
Chinese Journal of Plastic Surgery 2023;39(12):1331-1336
Objective:To analyze the vascular distribution of palmar digital arteries in syndactyly through color Doppler ultrasound angiography and make the classification according to the level of artery bifurcation points, discusse its clinical significance.Methods:A retrospective analysis was performed for the data of children with congenital and digital malformations admitted to Wuxi Ninth People’s Hospital from January 2017 to December 2022. Preoperative vascular ultrasonography of the hand was performed to locate the bifurcation point of the common palmar digital artery in the digital webbed area. The vascular conditions were classified according to the distance between the bifurcation point and the 1/3 point of the proximal phalangeal as the reference, such as normal type (<0 mm), mild reduction type (0-5 mm), moderate decrease type (6-10 mm), and severe reduction type (>10 mm), absent type (only 1 artery between the fingers). The total variation of the bifurcation point of the common palmar digital artery in the children, as well as the proportion of different vascular condition subtypes were recorded. According to the classification of blood vessels, the corresponding operation plan was made. The positioning accuracy of color Doppler ultrasound angiography was evaluated based on the gold standard of common palmar digital artery bifurcation points detected during operation. Complications such as postoperative infection, flap necrosis, finger vasospasm and the morphology of finger web at the last follow-up were observed. Descriptive statistical analysis was used.Results:A total of 123 children with 181 finger webs were enrolled, including 72 males and 51 females, aged 10-28 months. There were 55 cases of simple type, 36 cases of complex type (bone) and 32 cases of Poland syndrome. Color Doppler ultrasound angiography showed that the total variation rate of the common palmar digital arterial bifurcation point was 24.3% (44/181), of which 11.6% (21/181) were mildly reduced type, 8.3% (15/181) were moderately reduced type, 3.3% (6/181) were severe reduced type, and 1.1% (2/181) were absent type. The vascular variation rates of simple syndactyly, bony syndactyly, and Poland syndrome were 0 (0/55), 19.5% (7/36), and 41.1% (37/90), respectively. Compared with the actual situation during surgery, the positioning accuracy of color Doppler ultrasound angiography was 100%. All pediatric surgeries were successfully completed, and the flaps and skin grafts survived smoothly. There were no postoperative complications such as infection, vascular crisis, or finger necrosis. All patients were followed up for 6 to 27 months, with an average of 13.5 months. At the last follow-up, the depth, width, and slope of the fingerwebs were all close to normal.Conclusion:Congenital syndactyly has a high variation rate at the bifurcation point of the common palmar digital artery, and bony syndactyly and Poland syndrome refer to the need to improve preoperative vascular evaluation. Color Doppler ultrasound angiography has the advantages of no radiation, high sensitivity and low price, and the vascular typing based on color Doppler can improve the reliable basis for the formulation of clinical surgical plans.
7.Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway.
Shuhua SHAN ; Jinping NIU ; Ruopeng YIN ; Jiangying SHI ; Lizhen ZHANG ; Caihong WU ; Hanqing LI ; Zhuoyu LI
Acta Pharmaceutica Sinica B 2022;12(3):1254-1270
Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.
8.Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism.
Abi MAHARJAN ; Hongyu SUN ; Zeying CAO ; Ke LI ; Jinping LIU ; Jun LIU ; Tiqiao XIAO ; Guanyun PENG ; Junqiu JI ; Peter YORK ; Balmukunda REGMI ; Xianzhen YIN ; Jiwen ZHANG ; Li WU
Acta Pharmaceutica Sinica B 2022;12(5):2568-2577
Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.
9.Study on Therapeutic Effects and Its Mechanism of Jianpi Yiqi Decoction on Liver Cancer Model Rats
Chao WANG ; Zichen YUE ; Jinping YIN ; Xiao JIANG ; Shaoyuan ZHUO
China Pharmacy 2021;32(19):2342-2346
OBJECTIVE:To explore the therap eutic effects and its mech anism of Jianpi yiqi decoction on diethylnitrosamine (DEN)induced liver cancer model rats. METHODS :Totally 80 male SD rats were divided into normal group ,model group , Nod-like receptor family 3(NLRP3)inhibition group (MCC950,4.5 mg/kg),caspase-1 inhibitory group (VX-765,4.5 mg/kg), Jianpi yiqi decoction low-dose ,medium-dose and high-dose groups (5.25,10.5,21 g/kg),with 10 rats in each group except for 20 rats in model group (10 of them were only used to judge whether modeling was successful ). Rats in each group were intraperitoneally injected with DEN (70 mg/kg)to induce liver cancer model ,except for the rats in normal group which were replaced by normal saline. After modeling ,normal group and model group were given normal saline intragastrically ;inhibitor groups were given relevant medicine intraperitoneally ;Jianpi yiqi decoction groups were given relevant medicine intragastrically , once a day ,for consecutive 4 weeks. After last administration ,histopathological morphology of liver tissue was observed. The contents of serum inflammatory factors TNF-α and IL-1β were detected. The expression of NLRP3 and programmed cell necrosis associated protein (ASC,pro-caspase-1,RIP1,RIP3 and MLKL )in liver tissue were detected. RESULTS :Compared with the normal group ,the hepatocytes of model group showed varying, degrees of steatosis ,enlarged nuclei ,lumpy,bleeding and necrosis,accompanied by proliferative foci and nodules. Liver 198086, tissue injury index ,serum content of TNF-α and IL-1β as well as the protein expression of NLRP 3,ASC,pro-caspase-1,RIP1,RIP3 and MLKL in liver tissue were significantly increased (P<0.05 or P<0.01). Compared with model 防治。E-mail:sherwin_zhuo@126.com group,there were still a large number of inflammatory cell infiltration in the liver tissue of rats in Jianpi yiqi decoction low-dose and medium dose groups ,while the inflammatory cell infiltration of rats in high-dose group and inhibitor groups decreased significantly ;the liver tissue injury index and above indexes levels in serum and liver tissue were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS :Jianpi yiqi decoction shows therapeutic effect on liver cancer model rats ,the mechanism of which may be associated with down-regulating the expression of NLRP3 inflammasome and inhibiting programmed cell necrosis.
10.Effects of Ferulic Acid on the Proliferation ,Invasion and Apoptosis of HepG 2 Hepatocellular Carcinoma Cells
China Pharmacy 2021;32(13):1565-1571
OBJECTIVE:To study the effects of ferulic acid on t he proliferation ,invasion and apoptosis of HepG 2 hepatocelluar carcinoma cells. METHODS :CCK-8 assay was used to screen the concentration of ferulic acid. Western blot assay was adopted to screen the optimal concentration of interleukin 6(IL-6)to induce HepG 2 cell model with high expression of phosphorylated signal transduction protein and activator 3(p-STAT3)protein. HepG 2 cell were divided into blank control group , model group ,ferulic acid group (0.5 mmol/L)and positive control group (p-STAT3 inhibitor C 188-9,10 μmol/L). Except for blank control group ,model group treated with IL- 6,while administration groups were treated with IL- 6 and relevant drugs. Cell survival rate ,invasion and apoptosis rate in early and late stage were detected by CCK- 8 assay,Transwell assay and Annexin V-FITC/PI double staining ,respectively. Western blot assay was used to detect the expression of p-STAT 3,caspase-3,ZBP-89 and vimentin proteins in each group. On the basis of the PDB protein database ,using 1BG1,a highly similar crystal structure of STAT3,as docking template ,using the region around Tyr 705 as the putative binding pocket ,the docking analysis of ferulic acid with STAT 3 protein was carried out. RESULTS :It is selected to use 0.5 mmol/L ferulic acid intervention for 48 h as the follow-up experimental condition ;50 ng/mL IL- 6 was selected as the modeling condition. Compared with blank control group ,the number of cell invasion ,p-STAT3/STAT3 ratio and protein expression of vimentin were increased significantly in model group (P<0.05 or P<0.01),while late apoptosis rate and protein expression 20 of caspase- 3 were decreased significantly (P<0.05 or P< 0.01). Compared with model group ,cell survival rate ,the number of cell invasion ,p-STAT3/STAT3 ratio and protein expression of vimentin were d ecreased significantly in ferulic acid group and positive control group (P<0.05 or P<0.01);early apoptotic rate (except for ferulic acid group ),late apoptotic rate,the protein expression of caspase- 3 and ZBP- 89(except for positive control group )were increased significantly (P<0.05 or P<0.01). The results of molecular docking showed that the carboxylic groups of ferulic acid could interact with 1.9 Å hydrogen bond of Asn 581 and 2.0 Å hydrogen bond of Lys 591,with binding energy of -4.4 kcal/mol. CONCLUSIONS :Ferulic acid may inhibit the activity of p-STAT 3 by directly binding to the phosphorylation site of STAT 3;it may up-regulate the protein expression of caspase- 3 via STAT 3 dependent pathway ,or up-regulate the protein expression of ZBP- 89 via STAT 3 independent pathway and then down-regulate the protein expression of vimentin ,so as to inhibit the proliferation ,invasion and apoptosis of HepG 2 cells.

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