Pathological cardiac hypertrophy is an early and significant cardiac structural charac-teristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally en-larged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its no-vel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the an-giotensin II(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Fur-ther studies showed that siRNA-directed ARPC2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 com-plex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregu-lated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specif-ic Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of car-diomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regu-lates pathological cardiac hypertrophy.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Pathological cardiac hypertrophy is an early and significant cardiac structural charac-teristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally en-larged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its no-vel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the an-giotensin II(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Fur-ther studies showed that siRNA-directed ARPC2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 com-plex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregu-lated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specif-ic Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of car-diomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regu-lates pathological cardiac hypertrophy.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Actin polymerization is a crucial process in cellular functions,impacting key processes like cell division,development,morphogenesis,motility,and polarity establishment.Abnormalities in actin polymerization can lead to various diseases,including cancer,highlighting its significance in both normal cell function and disease progression.While the amino acid sequences of actin are highly conserved across species,recent studies have revealed differences in their polymerization functions.The animal or plant actin can be used heterologously in yeast cells,but certain types like the rabbit skeletal muscle and maize pollen actin have unique polymerization properties.On the other hand,the yeast actin can interact with the animal or plant actin.This review explores the polymerization characteristics of the animal,plant,and yeast actin,highlighting functional disparities in polymerization both in vivo and in vitro.Additionally,we discuss drugs that target actin polymerization,aiming to offer potential avenues for treating human diseases and advancing our understanding of actin's molecular mechanisms.Further research in this area may uncover the underlying principles of actin diversity and functional evolution,providing valuable insights for related fields.

Objective Exploring the occurrence and clinical characteristics of adverse drug reactions caused by the treatment of malignant hematological diseases in children with pegaspargase,in order to provide reference for safe drug use in clinical practice.Methods Summarize and organize 24 cases of adverse reactions related to pegaspargase reported in the pediatric hematology ward of our hospital from January 2016 to June 2023 for analysis and re evaluation.The basic information,severity of adverse drug reaction(ADR),dosage,route of administration,clinical manifestations,occurrence time and outcome of ADR were analyzed statistically.Results Among the 24 ADR reports,there were 15 males(62.50％)and 9 females(37.50％).The age ranged from 2 to 15 years,with an average age of(7.79±4.68)years.There were 16 children under 10 years old(66.67％).The primary disease is acute lymphocytic leukemia(87.50％).The administration mode of 24 patients was intramuscular injection,and the dosage was 1200-3 750 U.A total of 30 AD Rs occurred in 24 patients,10 of which were serious ADRs.The most common organ involved in ADR was gastrointestinal system damage(8 cases,27.59％),followed by systemic(6 cases,20.69％)and skin and Subcutaneous tissue(5 cases,17.24％).The shortest occurrence time of ADR is 5 minutes after medication,and the longest is 56 days after medication.Conclusion Clinical attention should be paid to the occurrence characteristics of asparaginase ADR.After medication,patients need to be monitored for safety over a long period of time,closely monitoring their clinical symptoms and related test indicators,especially in young children,to reduce the damage caused by ADR to patients.

The concept of ethnic medicine is divided into a broad sense and a narrow sense. The broad concept refers to the traditional medicine of the Chinese nation, and the narrow concept refers to the traditional medicine of Chinese ethnic minorities. The external medicine is one of the main forms of ethnic medicine, and it is also the important content of ethnic medicine for external use, which is widely used in clinical practice. As the theory of ethnic medicine is unique, the application methods have certain characteristics, which are the key technical parts of clinical practice. However, the existing traditional Chinese medicine consensus formulation me-thods cannot meet the needs of the consensus formulation of the external ethnic medicine. Therefore, the methods suitable for expert consensus on external ethnic medicine are required. This article took Expert opinion on clinical application of Baimai Ointment as an exa-mple, and explorde a reasonable, effective, multi-dimensional, and multi-stage method to formulate expert consensus on the external ethnic medicine. In this research, three-dimensional sources of information, including ancient classics, clinical research evidence, and expert application experiences, were systematically and scientifically collected. After organization and analysis, the information was formed into comprehensive evidence. In a formal consensus meeting, part of the recommendations reached consensus. As to the issues that did not reach agreement, in-depth interviews were used to explore the reasons for the differences and resolve the disagreements. Finally, unanimous recommendations were reached. There are common problems during the formulation process of Expert opinion on clinical application of Baimai Ointment. This study is expected to provide references for the formulation of expert consensus on other external ethnic medicine.
Humans ; Biological Products ; Consensus ; Drugs, Chinese Herbal

Objective:To compare the detection success rates (DSRs) of different kinds of near-infrared spectrum non-invasive hemoglobin monitors in high-altitude environments.Methods:One hundred and forty-four healthy volunteers of either sex, aged 18-50 yr, were assigned to one of 3 groups using a random number table method: simulated high-altitude 3 500 meter group ( n=35), 4 000 meter group ( n=55) and 4 500 meter group ( n=54). Hemoglobin was detected by Radical-7, NW-9002SHM, A5 and TensorTip MTX type hemoglobin monitors in plain environment and simulated environment at different altitudes, and the DSRs were compared.Logistic regression analysis was conducted to identify the risk factors affecting the success rate of instrument detection, and the cut-off value was determined by ROC curve and the Youden index. Results:In the simulated high-altitude environment of 3500, 4000 and 4500 m, the DSR of TensorTip MTX was significantly higher than that of Radical-7, NW-9002SHM and A5 ( P<0.001), and there was no significant difference in the DSR among Radical-7, NW-9002SHM and A5 ( P>0.05). Low SpO 2 was the main factor affecting the DSRs of the Radical-7, NW-9002SHM and A5 type hemoglobin monitor in high-altitude environment ( P<0.001), and the cut-off value of SpO 2 in determining the success of detection was 88.5%, 87.5% and 89.5%, respectively.The DSR of TensorTip MTX was not affected by low SpO 2. Conclusions:The DSR of TensorTip MTX hemoglobin monitor is minimally affected by the high-altitude environment and can be preferred in the absence of oxygen supply; when Radical-7, NW-9002SHM or A5 hemoglobin monitor applied in high-altitude environments, oxygen saturation needs to be increased to ensure a high DSR.

Bone Neoplasms ; Diagnosis, Differential ; Humans ; Osteoblastoma/surgery*

Six new bisabolane-type phenolic sesquiterpenoids, including plakordiols A-D (1-4), (7R, 10R)-hydroxycurcudiol (5) and (7R, 10S)-hydroxycurcudiol (6) were isolated from the marine sponge Plakortis simplex collected from the South China Sea. Their structures were determined based on extensive analysis of spectroscopic data. Their configurations were assigned by coupling constant analysis, NOESY correlations, and the modified Mosher's method. Furthermore, their cytotoxic and antibacterial activities were evaluated.
Animals ; Anti-Bacterial Agents/pharmacology* ; China ; Molecular Structure ; Monocyclic Sesquiterpenes/pharmacology* ; Pacific Ocean ; Plakortis/chemistry*