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.

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.

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.

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.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

AIM: To investigate the role of G-protein-coupled bile acid receptor 1 ( GPBR1; also known as TGR5) activation in high glucose-induced cardiomyocyte hypertrophy and calcineurin (CaN)/nuclear factor of activated T-cells 3 (NFAT3) signaling.METHODS:Primarily cultured mouse cardiomyocytes were used in the study .The cell surface areas of the cardiomyocytes were measured by an image analysis system .The cell protein content was detected by BCA meth-od.The expression of TGR5, CaN and NFAT3 at mRNA and protein levels was determined by RT-PCR and Western blot . RESULTS:The mouse cardiomyocytes were successfully cultured .High glucose significantly induced the increases in the cell surface area, the cell protein content and the expression of CaN and NFAT 3 (P<0.05) in the cardiomyocytes.TGR5 activation or a CaN antagonist cyclosporin A inhibited high glucose-induced cardiomyocyte hypertrophy and the expression of CaN and NFAT3 (P<0.05).These effects of TGR5 activation were abolished by TGR5 gene interference (P<0.05). CONCLUSION:TGR5 activation reduces high glucose-induced cardiomyocyte hypertrophy by inhibiting CaN /NFAT3 sig-naling.

Objective To establish a stable and fast method for primary culture of mouse cardiomyocytes. Methods Dishes were coated with polylysine firstly.A two-step approach was used to isolate and digest mouse cardiomyocytes cells (0.25%trypsin in 4°C overnight and 0.5 mg/mL to 1.0 mg/mL collagenase +5 mg/mL albumin collagen digestion liquid in 37°C for short-time digestion), then the cardiomyocytes were purified through differential adhesion for 70 min and 5-bromodeoxyuridine ( BrdU) .The cell morphology was observed under an inverted microscope. The survival rate of cardiacmyocytes was detected by trypan-blue staining and their purity was identified by α-actinin immunofluorescence staining.Results The cardiomyocytes were in good shape and pulsed spontaneously.The survival rate of the cardiomyocytes reached 98%and the purity was 95%.Conclusions This method described in this study is an ideal method for primary culture of mouse cardiomyocytes with a high survival rate and high purity.

Objective To explore the imaing features of hemangioma in the long bone and improve the diagnostic level of this disease. Methods The X-ray(14 cases), CT(9 cases) and MRI(6 cases)findings of 18 patientswith histologically proven hemangioma in the long bone after surgery were retrospectively reviewed. Results Ten tumors occurred in medullary cavity or bone end(medullary type),6 on the surface of bone (periosteal type) and 3 in cortex (intracortical type). X-ray findings: among 8 cases of medullary type, 3 showed honeycomb appearance, 3 lytic areas with sclerotic borders, one purely osteolyticchanges, and 1 frosted glass; 3 cases of periosteal type showed sclerosis and thickening of the underlying cortex; 3 cases of intracortical type showed well-defined osteolytic foci. CT findings: among 6 cases of medullary type, 5 appeared as expansile lytic lesion with uneven selerotic rim (3 cases)orhoneycomb appearance (2 cases), 1 cribriform appearance in the cortical bone, 2 periostealnew bone formation in vertical radiation pattern; 1 ground-glass appearance; among 2 cases of periosteal typeone showed regular cortical thickening, and the other irregular periosteal proliferation with marrowing of medullarycavity; 1 case of intracorticaltype showed density similar to that of soft tissue, with cortical thickening and expansion . MRI findings: 2 apeared as well-defined lesions with low signal intensity on T1WI and high signal intensity on T2WI; 1 appeared as ill-defined lesion with low to intermediate signal intensity on T1 WI and T2 WI. One showed breakthrogh of cortex and formation of soft tissue mass with low signal intensity on T1 WI and high signal on T2WI. Two showed thickening of periosteumwith intermediate signal intensity in one of them and very low signal intensity in the other. Two showed abnormal signal intensity in surrounding muscles, which was high on T2 WI and intermediate on T1 WI. Conclusions The soap-bubble or honeycomb appearance is the typical radiographic finding of hemangioma in long bone. CT and MRI can provide useful information for the diagnosis of hemangioma in long bone.

Objective To evaluate the detection of serum pepsinogen (PG) in screening of gastric cancer. Methods (1) To calculate the detection rate of gastric cancer in PG Positive patients from northeastern, noah-western and northern China. (2) To determine the PG positive rate in patients with chronic superficial and atrophic gastritis. (3) To calculate the detection rate of gastric cancer, H. pylori infection and esophageal cancer in PG positive patients from gastric cancer high risk areas. Results (1) The detection rate of gastric cancer in PC, positive patients from Changchun (northeastern China), Xihing (northwestern China) and Beijing ( northern China) was 22. 58%, 25. 2% and 0, respectively. The sensitivity of PG to seeen gastric cancer in Changchun and Xihing was 50. 9% and 35.6%, and the specificity was 82. 56% and 85.69%, respectively. (2) Only 25% of patients with chronic atrophic gastritis were PG positive. (3) The serum PG level was measured in 2346 cases from gastric cancer high risk areas, and PG positive rate was 27.02% (634/2346), in which 496 patients (76. 65%, 496/634) received endoscopy, and gastric cancer was detected in 10 (2. 02%, 10/496), including 9 cases of early gastric caner. The prevalence of gastric cancer was 0. 43% in common population and 1.58% in PG positive population. The infection rate of H. pylori was 70. 73% in 2346 subjects and 2 cases of esophageal cancer, including 1 case of early cancer was diagnosed. Conclusion Serum PG level cannot be used as a marker for gastric cancer or atrophic gastritis, while it may be of value for gastric cancer screening in high risk areas.

BACKGROUND:Psychological disorder and behavior disorders can affect the development of behavior and personality in children.OBJECTIVE:To investigate the behavior disorders and the personality in children with tic disorders (TD).DESIGN:A comparative investigation between TD children and the healthy controls.SETTING:It was conducted at the Department of Pediatrics,Daqing Oil Felid General Hospital in Heilongjiang ProvincePARTICIPANTS:Totally 110 outpatients including 92 males and 18females, diagnosed as TD at the Department of Pediatrics, Daqing Oil Felid General Hospital,were selected (TD group) from February 2003 to December 2004.According to the clinical manifestations,they were divided into transient tic disorder group (46 cases),chronic motor/vocal tic disorder group (34 cases) and Tourette Syndrom (TS) group(30 cases).All the patients were newly diagnosed without any medication and intracranial organic diseases. Meanwhile,30 children with normal physical examination findings, between the ages of 7 and 14,24 males and 6 females, were selected as controls. Informed consents were obtained from guardians of all the participants.used to measure the children's social skills and behaviors (It contains a 113-item behavior problems scale. According to the children's ages,the items were classified into 9 factors,including somatic complains,poor social skills,compulsions,undisciplined,hyperactivity,Asperger syndrome,immaturity,hostility and aggressiveness.The scores of referring items constitute the total score of each factor).Comparison of these scores between patients and healthy controls is helpful to determine if a factor in affected children is abnormal. The closer the relationship between the patients and the controls is, the less behavioral problems Personality Questionnaire (EPQ) was adopted in this study to evaluate the personality in the patients compared to healthy controls.{There were four major dimensions of personality including introversion/extraversion,neuroticism,psychoticism and validity questionnaire (construct validity).When the validity score was over 70,it represented that the EPQ was invalid.An over-61.5 neuroticism score represented an apparent neuroticism tendency. Once the neuroticism score and introversion/extraversion score were over 56.7,mental instability or instable tendency could be suspected. When introversion/extraversion score was over 56.7and the neuroticism (extraversion) score was less than 43.3,it represented a sanguine personality or such tendency. When both of the neuroticism score and introversion/extraversion score were less than43.3 (introversion),it revealed a phlegmatic personality or such tendency. And when the introversion/extraversion score was less than43.3 with neuroticism score over 56.7,it represented a melancholic personality or such tendency.}MAIN OUTCOME MEASURES:Comparison of Achenbach's CBCLand EPQ between patients and healthy controls .RESULTS:Totally 110 TD patients and 30 healthy children completed the control group (t=3.12-8.60, P ＜ 0.01).The hyperactivity score in the transient tic group was significantly higher than that in the control group (t=2.01, P ＜ 0.05). In the chronic motor tic disorder group and the TS group,the scores of depression/anxiety,poor social skills,compulsions,social withdrawal,hyperactivity and aggression were all higher than those in the control group(t=2.11-7.65, P ＜ 0.05-0.01).In all of these three TD groups, score factors relating to social functions,such as movements, social skills and school life were apparently lower than those in the control group (t= 1.97-7.31, P ＜ 0.05-0.01).(t=2.76-4.32, P ＜ 0.05-0.01), while the score of validity questionnaire was lower than that in control group (t=3.49-6.38, P ＜ 0.05).CONCLUSION:It reveals that TD patients have many behavioral problems,personality defects and poor social skills. Of all the TD groups,the transient tic group has a higher occurrence rate of disease and only one abnormal factor, hyperactivity. While,the chronic motor tic disorder group and the TS group have more abnormal behavioral factors.