ObjectiveTo investigate the effects of Maimendong Yinzi （MMDYZ） on cough with Yin deficiency and lung heat syndrome and explore its potential mechanism of action. MethodsForty-eight Institute of Cancer Research （ICR） mice were randomly divided into a control group， a model group， a Baihe Gujin Tablet （BHGJP） group （1.36 g·kg^-1）， and low-dose， medium-dose， and high-dose MMDYZ groups （5， 10， 20 g·kg^-1·d^-1， based on the weight of crude drug）， with eight mice in each group. The mouse model of cough with Yin deficiency and lung heat syndrome was prepared by a combination of smoke exposure， nasal drip of lipopolysaccharide （LPS）， intragastric gavage with thyroxine， and capsaicin atomization. After successful modeling， drug interventions were administered for seven days. During modeling， the mice were observed for changes in general status， anal temperature， fecal water content， and water intake. After medication， the above indicators were evaluated again， along with assessments of spontaneous activity， cough sensitivity， lung function， lung index， and tracheal phenol red secretion. Bronchoalveolar lavage fluid （BALF） was analyzed for cell differential counts， and the level of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in serum was measured via enzyme linked immunosorbent assay （ELISA）. Lung injury was assessed via hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict the potential mechanism of MMDYZ in alleviation cough with Yin deficiency and lung heat syndrome. Western blot （WB） was used to measure protease-activated receptor1 （PAR1） and GTPhase α_i subunit （Gα_i） protein expressions in lung tissue. ELISA was used to determine lung cAMP content， and immunohistochemistry （IHC） was employed to evaluate transient receptor potential vanilloid subtype 1 （TRPV1） expression. ResultsCompared with the control group， the model group exhibited significantly increased water intake and anal temperature and significantly decreased fecal water content （P<0.05）. The total distance traveled in 5 min and the central zone duration were reduced， while standing frequency significantly increased （P<0.05）. Cough sensitivity and enhanced pause （PenH） were elevated. Peak expiratory flow （PEF） significantly declined （P<0.05）. BALF neutrophil （NEU） and white blood cell （WBC） counts rose. Serum cAMP and cAMP/cGMP ratio significantly increased， and cGMP significantly decreased （P<0.05）. Serum TNF-α and IL-6 levels were significantly elevated （P<0.05）. The lung injury was obvious， and the lung index was significantly elevated （P<0.05）. Compared with the model group， the medium-dose and high-dose MMDYZ groups and the BHGJP group showed significantly improved indicators mentioned above. Additionally， network pharmacology suggested that MMDYZ might alleviate cough with Yin deficiency and lung heat syndrome via cAMP， hypoxia inducible factor-1 （HIF-1）， and TNF signaling pathways. WB， ELISA， and IHC revealed that， compared with the control group， the model group exhibited significantly upregulated PAR1， Gα_i， and TRPV1 expressions and significantly downregulated cAMP in lung tissue （P<0.05）. Compared with the model group， MMDYZ reduced PAR1 （P<0.01）， Gα_i （P<0.05）， and TRPV1 （P<0.01） while increasing cAMP level （P<0.01）. ConclusionMMDYZ may alleviate cough with Yin deficiency and lung heat syndrome by modulating the PAR1/Gα_i/cAMP pathway and TRPV1 expression.

Objective To investigate the influencing factors associated with the comorbidity of inflammatory bowel disease (IBD) and depression. Methods A case-control study was conducted based on the ^“Healthcare Big Data Platform^” of a tertiary class-A comprehensive hospital in Shandong Province. IBD comorbid with depression was served as the case group and IBD without depression was served as the control group. Propensity score matching (PSM) was performed by matching the case group with the control group in a ratio of 1:2 according to the age and gender of the patients. Conditional logistic regression model was used to explore the influencing factors associated with the comorbidity of IBD and depression. Results A total of 405 patients with IBD were enrolled in this study, including 270 patients without depression and 135 patients comorbid with depression. The results of conditional logistic regression showed that the use of immunosuppressants (OR=2.84, 95% CI: 1.00-8.07) and glucocorticoids (OR=2.05, 95% CI: 1.17-3.58), dementia (OR=5.20, 95% CI:1.59-17.05), cardiovascular disease (OR=3.58, 95% CI: 1.84-6.98) and cancer (OR=2.63, 95% CI: 1.16-5.95) were associated with the comorbidity of depression and IBD. Conclusion Attention should be paid to the use of immunosuppressants and glucocorticoids in the population of IBD comorbid with depression, and the coexistence of physical diseases such as dementia, cardiovascular disease and cancer. Early prevention and targeted treatment measures should be taken for high-risk populations to reduce their risk of depression and improve their quality of life and health.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

Objective:To establish the characteristic spectrum of Liushenqu standard decoction using ultra-high performance liquid chromatography (UPLC); To determine the contents of related index components; To evaluate the quality of Liushenqu standard decoction.Methods:UPLC method was used to establish characteristic spectrum of Liushenqu standard decoction. Chromatographic Fingerprint Similarity Evaluation System (2012 edition) was used for similarity analysis, the characteristic peak was assigned, and the content of its index components was determined.Results:The characteristic peaks of Liushenqu standard decoction were calibrated and 8 components were identified, namely uridine, adenosine, guanosine, 5-hydroxymethylfurfural, tryptophan, vanillic acid, ferulic acid and shaftaside. The contents of uridine, adenosine, tryptophan ferulic acid and shaftaside in 10 batches of Liushenqu standard decoction were simultaneously determined, and ranged from 0.036 1～0.383 9 mg/g, 0.030 7～0.170 2 mg/g, 0.007 0～0.060 2 mg/g, 0.001 0～0.005 0 mg/g, 0.000 8～0.013 8 mg/g, respectively. The transfer rates ranged from 44.2% to 50.8%, 60.1% to 67.7%, 60.4% to 76.4%, 62.7% to 77.4%, 50.7% to 61.4%, respectively.Conclusion:The established UPLC characteristic spectrum and content determination method are accurate and repeatable, which can provide references for quality control of Liushenqu standard granules.

Objective:To establish UPLC characteristic spectrum of Hujiao standard decoction and the determination method for the content of piperine.Methods:15 batches of freeze-dried powder of Hujiao standard decoction were prepared according to the traditional decocting method. The range of paste yield was determined, and the UPLC characteristic spectrum of the standard decoction was established. High-resolution mass spectrometry and control products were used to identify common peaks. Based on the common peak area, the weights of each peak were compared using entropy weight method, and correlation analysis and similarity evaluation were conducted using clustering analysis and grey correlation method; a method for determining the content of piperine in Hujiao decoction pieces and freeze-dried powder of standard decoction was simultaneously established, and the transfer rate was calculated.Results:The extraction rate of 15 batches of freeze-dried powder of Hujiao standard decoction ranged from 10.4% to 16.8%, with an average of 14.0%. The content of piperine ranged from 12.2 to 30.0 mg/g, with an average of 18.5 mg/g, and the transfer rate ranged from 4.0% to 7.8%, with an average of 5.8%. Six common peaks were identified in the established characteristic spectrum and identified by high-resolution mass spectrometry and control products respectively. Peak 1 was N-trans-feruloyltyramine, peak 3 was piperine and the similarity was 0.959-1.000. Clustering analysis and grey correlation analysis showed that there was little difference between quality of Piperis Fructus and origins.Conclusion:In this study, the characteristic spectrum and content determination method of freeze-dried powder of Hujiao standard decoction are established, which can provide references for quality detection and control of Hujiao standard decoction or its derivative products.

Objective To analyze the efficacy of different intracavitary operations for calyceal diverticulum calculi,so as to provide reference for the diagnosis and treatment of such disease.Methods A retrospective analysis of the data of 21 patients with calyceal diverticulum calculi was conducted during Jan.2015 and Dec.2021.The patients were divided into the retrograde intrarenal surgery(RIRS,n=14)group and percutaneous nephrolithotomy(PCNL,n=7)group.The perioperative data were compared.Results There was no significant difference in stone load between the RIRS group and PCNL group[(11.56±4.79)mm vs.(13.06±6.27)mm,P=0.609].There were significant differences in the thickness of renal parenchyma at the top of the diverticulum[(10.08±4.81)mm vs.(5.24±2.23)mm,P=0.005],operation time[(58.57±19.23)min vs.(88.29±25.28)min,P=0.007],hospitalization time[3(1,5)vs.12(5,7),P=0.023]days.After operation,there were no significant differences in stone-clearance rate,decrease of hemoglobin,and postoperative complications between the two groups(P＞0.05).Conclusion Both RIRS and PCNL are viable options for treating renal calyceal diverticulum calculi.RIRS has advantages of shorter operation time and hospital stay.PCNL can be an alternative treatment when RIRS is unsuccessful.

OBJECTIVE To investigate the effect of Huangqi-Ezhu-Chonglou combination on macrophage polarization and its mechanism of inhibiting colorectal cancer(CRC)cells proliferation and migration.METHODS THP-1 cells were stimulated with phorbol 12-myristate 13-acetate(PMA)and interleukin-4(IL-4)to establish M2 macrophage polarization model.The experiment was divided into M0 group(PMA treatment),M2 group(PMA+IL-4 treatment),and M2+ Huangqi-Ezhu-Chonglou combination group(PMA+IL-4+Huangqi-Ezhu-Chonglou combination treatment).The effect of Huangqi-Ezhu-Chonglou combination freeze-dried powder on the viability of macrophage was detected by CCK-8 method.The expression of macrophage polarization markers,glu-taminase(GLS)mRNA and protein was detected by qPCR and Western blot.The levels of interleukin-10(IL-10),transforming growth factor-β(TGF-β)and tumor necrosis factor-α(TNF-α)in cell supernatant were detected by ELISA.CCK-8 method and Tr-answell assays were used to detect the proliferation and migration of HCT116 cells intervened by the supernatant of macrophage culture treated with Huangqi-Ezhu-Chonglou combination,namely conditioned medium(CM).RESULTS Compared with the M0 group,the expression levels of IL-10,mannose receptor(CD206),arginase 1(ARG1),and GLS mRNA and protein in the M2 group were significantly increased(P<0.01,P<0.001),the levels of IL-10 and TGF-β secreted by macrophages were significantly increased(P<0.01,P<0.001);compared with the M2 group,the M2+ Huangqi-Ezhu-Chonglou combination group had significantly reduced IL-10,CD206,ARG1,and GLS mRNA and protein expression(P<0.05,P<0.01),the mRNA and protein levels of TNF-α and in-ducible nitric oxide synthase(iNOS)were significantly increased(P<0.05,P<0.01,P<0.001),the interleukin-1β(Interleukin-1β,IL-1β)mRNA expression significantly increased(P<0.01),and the contents of IL-10 and TGF-β in the cell supernatant sig-nificantly decreased(P<0.05,P<0.01),while TNF-α content significantly increased(P<0.01).CCK-8 and Transwell results showed that compared with the M0-CM group,the M2-CM promoted the proliferation and migration of HCT116 cells(P<0.01,P<0.001),the M2+ Huangqi-Ezhu-Chonglou-CM group significantly inhibited HCT116 cell proliferation and reduced cell migration compared to the M2-CM group(P<0.01,P<0.001).CONCLUSION Huangqi-Ezhu-Chonglou combination can inhibit colorectal cancer cells proliferation and migration by regulating macrophage polarization,and its mechanism may be related to the changes in the expression of GLS,a key enzyme in glutamine metabolism.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.