ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1 ^+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity-collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Objective To investigate the protective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on the pulmonary arterial hypertension(PAH)model induced by monocrotaline(MCT)/monocrotaline pyrrole(MCTP)in SD rats/human pulmonary artery endothelial cell(HPAEC).Methods In vivo experiment,60 male SD rats were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(20 mg/kg)group,AS-Ⅳ medium-dose(40 mg/kg)group,AS-Ⅳ high-dose(80 mg/kg)group,or sildenafil(Sil,100 mg/kg)group,with 10 rats in each group;except for the control group,PAH rat models were established by single intraperitoneal injection of MCT(60 mg/kg)in other groups.In vitro experiment,HPAECs were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(10 μmol/L)group,AS-Ⅳ medium-dose(20 μmol/L)group,MCTP+AS-Ⅳ high-dose(40 μmnol/L)group,or p38 mitogen-activated protein kinase(MAPK)signaling pathway inhibitor(SB203580,5 μmol/L)group;except for the control group,in vitro PAH cell models were established by MCTP(60 μg/mL)induction for 24 h in other groups.In vivo experiments,after 4 weeks of drug intervention,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)of rats were measured by hemodynamic methods,the right ventricle hypertrophy index was measured by weighing methods,the percentage of pulmonary arteriole wall thickness to outer diameter(WT％)and percentage of the wall area to total vascular area(WA％)were observed by hematoxylin-eosin staining,the expression of cysteine aspartic acid specific protease 3(caspase 3)protein in lung tissue was observed by immunohistochemistry(IHC),and the apoptosis of lung tissue cells was detected by TUNEL assay.In vitro experiments,JC-1 staining was used to detect the mitochondrial membrane potential in cells,and immunofluorescence was used to detect caspase 3 protein expression.In vitro and in vivo experiments,Western blotting was used to detect the expression of caspase 3,B-cell lymphoma gene 2(Bcl-2),Bcl-2 associated X protein(Bax),p38 MAPK,and phosphorylated p38 MAPK proteins in lung tissue and HPAECs.Results In vivo experiments,the RVSP,mPAP,and right ventricle hypertrophy index were decreased in the Sil group and each dose group of AS-Ⅳ(all P＜0.01);the WA％and WT％of each dose group of AS-Ⅳ were decreased(all P＜0.01),the expression of caspase 3 protein in lung tissue was decreased(all P＜0.01),and the apoptosis of lung tissue cells was decreased(all P＜0.01).In vitro experiments showed that after intervention with each dose of AS-Ⅳ and SB203580,the mitochondrial membrane potential of HPAEC was increased(all P＜0.01)and the expression of caspase 3 was decreased(all P＜0.01).In vivo and in vitro experiments,each dose of AS-Ⅳand SB203580 reduced the expression of Bax and phosphorylated p38 MAPK proteins,and increased the expression of Bcl-2 protein(all P＜0.01).Conclusion AS-Ⅳ reduces apoptosis by inhibiting p38 MAPK signaling pathway,improving PAH in SD rats.

ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.

ObjectiveTo discuss the effects of Cistanches Herba phenylethanoid glycosides （CHPhGs） on the intestinal mucosal barrier and gut microbiota in alcoholic liver disease （ALD） mice were discussed. MethodThe 36 C57BL/6N female mice were randomly divided normal group， normal group of CHPhGs， model group， and low， medium， and high-dose groups （175， 350， 700 mg·kg^-1） of CHPhGs， with six mice in each group. The ALD mouse model was built using Lieber-Decarli alcohol liquid feed. The normal group and low， medium， and high-dose groups of CHPhGs were given CHPhGs by gavage daily. Serum aspartate aminotransferase aminotransferase （ALT）， alanine aminotransferase （AST）， triglycerides （TG）， and total cholesterol （TC） levels were detected by an automatic biochemical analyzer. Serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， lipopolysaccharide-binding protein （LBP）， D-lactic acid （D-LA）， diamine oxidase （DAO）， and LBP of liver were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of TG and TC in the liver were detected by colorimetry. Liver tissue was treated by oil red O and hematoxylin-eosin （HE） staining. The microstructure of jejunum epithelial cells was observed by electron microscope. Jejunum and colon were treated by HE staining and alcian blue-periodate-scheff (AB-PAS) staining staining， and mucin 2 （Muc2） was treated by immunohistochemistry. The intestinal contents of the normal group， normal group of CHPhGs， model group， and high-dose group of CHPhGs were collected and sequenced. ResultThe ALD model was established successfully. Compared with the normal group， the levels of serum ALT， AST， and TG， as well as the levels of liver TG and TC in the model group were significantly increased （P<0.05）. Histopathology showed that compared with the normal group， the liver cells in the model group showed obvious steatosis. Compared with the model group， the levels of serum TG and liver TG and TC in the low， medium， and high-dose groups of CHPhGs decreased significantly （P<0.05）. The serum ALT， AST， TNF-α， IL-1β， LPS， and LBP in the high-dose group of CHPhGs were also significantly decreased （P<0.05）. The number of liver cells with steatosis in the high-dose group of CHPhGs was significantly reduced， and the microvilli structure of jejunum epithelial cells was basically intact. The expression of Muc2 was reduced in the colon， and the gut microbiota of the high-dose group of CHPhGs changed significantly （P<0.05）. Compared with the normal group， the Allobaculum was significantly up-regulated in the model group （P<0.05）. Compared with the model group， the abundance of Akkermansia in the high-dose group of CHPhGs was significantly increased （P<0.01）. The abundance of Akkermansia was negatively correlated with that of Allobaculum （r=-0.701， P<0.01）. ConclusionCHPhGs can reduce the intestinal barrier injury caused by ALD， which may play a protective role by regulating the abundance and structure of Akkermansia and Allobaculum and affecting the homeostasis of intestinal mucus.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.