1.Effect of extracellular matrix stiffness on tumor progression and treatment strategies
Lijuan WU ; Zhenfei WANG ; Xiaohui TAN ; Yingcai WU ; Yanling ZHENG ; Fengxue DAI
Chinese Journal of Tissue Engineering Research 2025;29(20):4286-4294
BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.
2.Lipidomics-Based Study on the Mechanism of Sanhan Huashi Formula in Treating Respiratory Syncytial Virus Pneumonia Model Mice
Yuqing ZHU ; Keyu TAO ; Yingcai XIONG ; Jiru ZHANG ; Zhaowei ZHANG ; Xiaoqing ZHOU ; Jiani TAN ; Jianjian JI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(11):1480-1492
OBJECTIVE To investigate the therapeutic effect of Sanhan Huashi Formula(SHF)on respiratory syncytial virus(RSV)-infected mouse models and explore its potential antiviral and anti-inflammatory mechanisms using lipidomics.METHODS Fifty-four BALB/c mice were randomly divided into six groups(n=9):blank group,model group,Ribavirin group(50 mg·kg-1·d-1),and SHF high(15.46 g·kg-1·d-1),medium(7.73 g·kg-1·d-1),and low-dose(3.87 g·kg-1·d-1)groups.A pneumonia model was established by in-tranasal RSV infection,followed by three consecutive days of oral gavage administration.Lung tissues were collected for histopathologi-cal evaluation using hematoxylin-eosin(HE)staining and inflammation scoring.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to measure mRNA levels of viral gene fusion protein(F),glycoprotein(G),and inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)to assess lung viral load and inflammation,while immunofluorescence staining was performed to observe the expression of RSV-F protein in lung tissues.Serum lipidomics analysis was conducted using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q Exactive Or-bitrap MS)to identify lipid metabolism changes and differential lipids.RESULTS Compared with the blank group,mice in the model group exhibited marked pulmonary inflammatory cell infiltration and tissue injury,with significantly elevated pulmonary histopa-thology scores and lung index.The lung viral load and the mRNA expression levels of the inflammatory factors TNF-α and IL-6 were significantly increased,and immunofluorescence likewise indicated high expression of RSV-F protein in lung tissue.Relative to the model group,treatment with SHF at all tested doses clearly ameliorated lung tissue injury,effectively suppressed viral gene expression and inflammatory cytokine levels,and reduced the fluorescence signal intensity of RSV-F protein in the lungs.Lipidomics analysis re-vealed that compared with the blank group,the model group exhibited marked disturbances in lipid metabolism-characterized by dys-regulation of triacylglycerol(TG),phosphatidylcholine(PC),lysophosphatidylcholine(LPC),sphingomyelin(SM),diacylglycerol(DG),lysophosphatidylethanolamine(LPE),and phosphatidylethanolamine(PE).High-dose SHF treatment reversed these RSV-induced lipid abnormalities.CONCLUSION SHF effectively alleviates RSV-induced pulmonary inflammation and pathological injury,re-duces pulmonary RSV viral load,and may exert these effects by modulating dysregulated lipid metabolism in peripheral blood.
3.Cross-kingdom Regulation by Plant miRNAs and Its Implications for the Study of Medicinal Substances of Traditional Chinese Medicine
Miao ZHANG ; Xiaohui TAN ; Yingcai WU ; Yanling ZHENG ; Lijuan WU ; Zhenfei WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):924-930
MicroRNA(miRNA),an important type of non-coding RNAs existing widely in viruses and eukaryotes,regulate gene expression at transcriptional and post-transcriptional levels.Recent studies have demonstrated that plant miRNAs could enter microorganisms,animals and human bodies to affect their physiological and pathological processes by cross-kingdom regulation of gene expression.This review summarized the current knowledge of cross-kingdom regulation of gene expression by plant miRNAs,introduced the research progress in intervention of human diseases with plant miRNAs,including anti-virus,anti-tumor,anti-inflammation,immune regulation,anti-fatigue,anti-fibrosis,vascular protection,nerve protection,etc.,and analyzed the reasons why plant miRNAs remain stable in vivo and in vitro and the underlying mechanisms how they regulate human gene expression.Furthermore,the impact of cross-kingdom regulation by plant miRNAs on exploring new active ingredients of traditional Chinese herbs and elucidating their pharmacology were evaluated.Finally,"constructing the complex regulatory network of traditional Chinese medicine miRNAs in human body"and"exploring new mechanisms of gene expression regulation by traditional Chinese medicine miRNAs"were pointed out,which were two scientific problems worthy of further investigation.
4.Cross-kingdom Regulation by Plant miRNAs and Its Implications for the Study of Medicinal Substances of Traditional Chinese Medicine
Miao ZHANG ; Xiaohui TAN ; Yingcai WU ; Yanling ZHENG ; Lijuan WU ; Zhenfei WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):924-930
MicroRNA(miRNA),an important type of non-coding RNAs existing widely in viruses and eukaryotes,regulate gene expression at transcriptional and post-transcriptional levels.Recent studies have demonstrated that plant miRNAs could enter microorganisms,animals and human bodies to affect their physiological and pathological processes by cross-kingdom regulation of gene expression.This review summarized the current knowledge of cross-kingdom regulation of gene expression by plant miRNAs,introduced the research progress in intervention of human diseases with plant miRNAs,including anti-virus,anti-tumor,anti-inflammation,immune regulation,anti-fatigue,anti-fibrosis,vascular protection,nerve protection,etc.,and analyzed the reasons why plant miRNAs remain stable in vivo and in vitro and the underlying mechanisms how they regulate human gene expression.Furthermore,the impact of cross-kingdom regulation by plant miRNAs on exploring new active ingredients of traditional Chinese herbs and elucidating their pharmacology were evaluated.Finally,"constructing the complex regulatory network of traditional Chinese medicine miRNAs in human body"and"exploring new mechanisms of gene expression regulation by traditional Chinese medicine miRNAs"were pointed out,which were two scientific problems worthy of further investigation.
5.Lipidomics-Based Study on the Mechanism of Sanhan Huashi Formula in Treating Respiratory Syncytial Virus Pneumonia Model Mice
Yuqing ZHU ; Keyu TAO ; Yingcai XIONG ; Jiru ZHANG ; Zhaowei ZHANG ; Xiaoqing ZHOU ; Jiani TAN ; Jianjian JI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(11):1480-1492
OBJECTIVE To investigate the therapeutic effect of Sanhan Huashi Formula(SHF)on respiratory syncytial virus(RSV)-infected mouse models and explore its potential antiviral and anti-inflammatory mechanisms using lipidomics.METHODS Fifty-four BALB/c mice were randomly divided into six groups(n=9):blank group,model group,Ribavirin group(50 mg·kg-1·d-1),and SHF high(15.46 g·kg-1·d-1),medium(7.73 g·kg-1·d-1),and low-dose(3.87 g·kg-1·d-1)groups.A pneumonia model was established by in-tranasal RSV infection,followed by three consecutive days of oral gavage administration.Lung tissues were collected for histopathologi-cal evaluation using hematoxylin-eosin(HE)staining and inflammation scoring.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to measure mRNA levels of viral gene fusion protein(F),glycoprotein(G),and inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)to assess lung viral load and inflammation,while immunofluorescence staining was performed to observe the expression of RSV-F protein in lung tissues.Serum lipidomics analysis was conducted using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q Exactive Or-bitrap MS)to identify lipid metabolism changes and differential lipids.RESULTS Compared with the blank group,mice in the model group exhibited marked pulmonary inflammatory cell infiltration and tissue injury,with significantly elevated pulmonary histopa-thology scores and lung index.The lung viral load and the mRNA expression levels of the inflammatory factors TNF-α and IL-6 were significantly increased,and immunofluorescence likewise indicated high expression of RSV-F protein in lung tissue.Relative to the model group,treatment with SHF at all tested doses clearly ameliorated lung tissue injury,effectively suppressed viral gene expression and inflammatory cytokine levels,and reduced the fluorescence signal intensity of RSV-F protein in the lungs.Lipidomics analysis re-vealed that compared with the blank group,the model group exhibited marked disturbances in lipid metabolism-characterized by dys-regulation of triacylglycerol(TG),phosphatidylcholine(PC),lysophosphatidylcholine(LPC),sphingomyelin(SM),diacylglycerol(DG),lysophosphatidylethanolamine(LPE),and phosphatidylethanolamine(PE).High-dose SHF treatment reversed these RSV-induced lipid abnormalities.CONCLUSION SHF effectively alleviates RSV-induced pulmonary inflammation and pathological injury,re-duces pulmonary RSV viral load,and may exert these effects by modulating dysregulated lipid metabolism in peripheral blood.
6.Effect of extracellular matrix stiffness on tumor progression and treatment strategies
Lijuan WU ; Zhenfei WANG ; Xiaohui TAN ; Yingcai WU ; Yanling ZHENG ; Fengxue DAI
Chinese Journal of Tissue Engineering Research 2025;29(20):4286-4294
BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.
7.Association of ZP4 gene polymorphism with primary open-angle glaucoma in an ethnic Chinese population from Sichuan province.
Yingcai TAN ; Dingding ZHANG ; Bo GONG ; Xiaohuan ZHANG ; Linxin JIANG ; Ying LIN
Chinese Journal of Medical Genetics 2018;35(5):737-740
OBJECTIVETo assess the association of single nucleotide polymorphisms (SNP) rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4) gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from Sichuan Province.
METHODSA dye terminator-based SNaPshot method was used to genotype 336 patients with POAG and 768 healthy controls.
RESULTSNo significant difference was detected in allelic frequencies of rs547984, rs540782, rs693421 and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG and the control groups (P<0.05).
CONCLUSIONZP4 gene SNPs rs547984, rs540782, rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.
8.Diagnosis and treatment of extraperitoneal pneumatosis caused by perforation of rectal diverticulum
Yang LI ; Lianyang ZHANG ; Tao WANG ; Shijin SUN ; Hao TAN ; Yingcai LI
Chinese Journal of Digestive Surgery 2013;(7):553-555
Rectal diverticulum is rarely seen in clinical practice.Perforation or rupture of rectal diverticulum with symptoms and signs of acute diffuse peritonitis makes it easily be misdiagnosed as appendicitis,rectal neoplasms,intestinal obstruction and other abdominal diseases.In this article,a retrospective analysis of the clinical data of one patient with extraperitoneal pneumatosis caused by perforation of rectal diverticulum was performed to investigate the diagnosis and treatment of the disease.
9.Diagnosis and treatment of postoperative complicated abdominal infections in abdominal injuries
Shijin SUN ; Hao TAN ; Tao WANG ; Yingcai LI ; Yuanzhang YAO ; Lianyang ZHANG
International Journal of Surgery 2011;38(11):738-741
Objective Because of high incidence rate of complicated postoperative abdominal infections in abdominal injuries and difficulty in their clinical diagnosis and treatment,this article aimed to investigate the mechanism and the surgical tactics for this kind of complication.Methods Totally 48 abdominal-injured cases of postoperative complicated abdominal infections in our hospital from July 2005 to December 2010 were reviewed.These patients (Male 30,Female 18) aged 16-70 (mean 38) years.There were 20 cases of simple abdominal injuries,and 28 cases of multiple injuries ( ISS 16 - 52,mean 24.42).The complicated postoperative abdominal infections included abdominal incision infections (25cases),intra-abdominal infections( 18 cases) and retroperitoneal infections(5 cases).Forty cases were transferrted from other hospitals to our hospital 2 - 76 days after trauma.16 of which underwent exploratory laparotomy at other hospitals after injury,and 8 cases were directly transferred to our hospital after injury.Results All patients finally had a definite diagnosis by abdominal checking(26 cases),paracentesis(5 cases),ultrasound and CT scan ( 12 cases),and PET/CT scan (5 cases)in our hospital,and were confirmed by cultiure of pathogenic bacteria.The treatment included vacuum sealing drainage (VSD) (25 cases),percutaneous imaging- guided abdominal abscess drainage(13cases) and re-laparotomy ( 10 cases).Successfull treatment was achieved in 46 patients,death in 2 patients.The causes of death consisted of 1 case of severe craniocerebral injury,1 case of MODS.Conclusions Complicated abdominal infections often occurs after the operations of abdominal injuries.attentively abdominal checking,paracentesis,and CT scan repeatedly were proofs to benefit the finally diagnosis.VSD therapy is a simple and effective method for abdominal incision complication,and dynamic CT scan and prompt exploratory laparotomy can improve patients' prognosis.

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