Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 in-flammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the met-formin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson stai-ning was performed to observe the morphology and fi-brosis of myocardial tissue.TUNEL staining was per-formed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP and β-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleaved-caspase-1,GSDMD and GSDMD-NT in myocardial tis-sue.Results DJC could alleviate myocardial patho-logical damage,reduce collagen deposition and apopto-sis,reduce the levels of blood glucose,blood lipid,myo-cardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP and β-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,prob-ably by inhibiting the activation of NLRP3 inflamma-somes,attenuating cardiomyocyte pyroptosis,and amel-iorating the inflammatory state.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Aim To study the possibility of luteolin(LUT)as a new drug of traditional Chinese medicine and its improving effect on glucose and lipid metabo-lism and liver oxidative stress injury in db/db mice,and to explore the possible mechanism.Methods AI was used to predict the drug toxicity,evaluate the phys-ical and chemical properties and segment the molecular structure of LUT.Molecular docking was used to verify the binding ability of LUT with Nrf2 and HMOX1;db/m mice were divided into the group C,and db/db mice were randomly divided into the T,L,M,H and P groups.The body weight and FBG changes were ob-served within 12 weeks of intervention.The expres-sions of FBG,HbA1c,Fins,TC,TG,HDL-C,LDL-C were detected.The pathomorphological changes and steatosis of mouse liver were observed by HE and oil red O staining.The expression of MDA,SOD and GSH-Px in liver was detected by Kit.The protein and mRNA expressions of Nrf2 and HMOX1 were detected by immunohistochemistry,WB and qPCR.Results AI algorithm predicted the safety and easy synthesis of LUT.LUT intervention had no significant effect on the body weight of db/db mice.After 12 weeks,compared with the group C,the livers of mice in group T showed disordered structure of hepatic lobules,irregular ar-rangement of hepatocytes,and a large number of fat vacuoles and lipid droplets in the cytoplasm.Compared with the group T,LUT intervention could improve the pathological changes of liver,reduce the expression of FBG,HbA1c,fins,TC,TG,LDL-C,MDA,improve the level of HOMA-IR,and upregulate the activities of SOD and GSH-Px.Molecular docking results showed LUT had strong binding with Nrf2 and HMOX1,and could increase the expression of Nrf2 and HMOX1.Conclu-sion LUT can correct the disorder of glucose and lip-id metabolism in db/db mice,and improve the level of oxidative stress in liver of mice through Nrf2/HMOX1 pathway,which has the development prospect as a new Chinese medicine for the treatment of T2DM.

Objective:To explore the diagnostic value of shear wave elastography(SWE)for clinically significant prostate cancer(csPCa).Methods:We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer(PCa)in Baoji Central Hospital from June 2017 to July 2023.All the patients underwent the following examinations in the order of serum prostate-spe-cific antigen(PSA)testing,transrectal ultrasonography(TRUS),measurement of the stiffness of the entire prostate gland by SWE,and TRUS-guided prostate puncture biopsy.The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base,middle,and apex of the prostate,including the maximum Young's modulus(Emax),mean Young's modulus(Emean),and minimum Young's modulus(Emin).We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results,focusing on their diagnostic performance for csPCa.Results:Of the 359 cases,189 were diag-nosed by pathological puncture biopsy as BPH,26 as non-csPCa,and 144 as csPCa.The PSA level,Emax,Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups(all P＜0.01),but showed no statistically significant difference between the BPH and non-csPCa groups(all P＞0.05).The area under the receiver operating characteristic curve(AUC),optimal cut-off value,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accura-cy of Emax in the diagnosis of csPCa were 0.852,143.92 kPa,72.22％,84.65％,75.91％,81.98％and 79.67％;those of Emean were 0.868,82.42 kPa,67.36％,91.16％,83.62％,80.66％and 81.62％;and those of Emin were 0.682,32.73 kPa,47.22％,89.30％,73.91％,71.54％and 72.14％,respectively.In the non-csPCa group,Emax,Emean and Emin were found be-low the optimal cut-off value in 73.08％(19/26),92.31％(24/26)and 88.46％(23/26),respectively.Conclusion:The stiff-ness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa,reduces unnecessary detection of non-csPCa,and provides some reference for its active surveillance.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 in-flammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the met-formin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson stai-ning was performed to observe the morphology and fi-brosis of myocardial tissue.TUNEL staining was per-formed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP and β-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleaved-caspase-1,GSDMD and GSDMD-NT in myocardial tis-sue.Results DJC could alleviate myocardial patho-logical damage,reduce collagen deposition and apopto-sis,reduce the levels of blood glucose,blood lipid,myo-cardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP and β-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,prob-ably by inhibiting the activation of NLRP3 inflamma-somes,attenuating cardiomyocyte pyroptosis,and amel-iorating the inflammatory state.

Objective Exploring the therapeutic mechanism of Yishen Jiangzhuo Granules(YSJZG)on chronic kidney disease(CKD)based on mitochondrial dynamics and apoptosis of renal tubular epithelial cells.Methods The CKD model of rats with 5/6 nephrectomy was adopted and divided into 6 groups according to random number table:sham operation control group,model group,emodin group(500 mg/kg/d),Yishen Jiangzhuo granule low,middle and high dose groups.After 8 weeks of treatment with YSJZG,serum creatinine(SCR)and urea nitrogen(BUN),pathological changes of renal cortex,mitochondrial morphology and ultrastructure were detected,and mitochondrial kinetic protein in renal tubular epithelial cells was detected by immunohistochemistry(Drp1,Fis1)and fusion proteins(Opa1,Mfn1)were detected by Western blot,and apoptotic proteins(CytC,Bax)in cytoplasm and mitochondria were detected by real-time PCR.Results Renal injury:Compared with the model group,YSJZG groups significantly reduced the levels of SCR and BUN,renal tubular degeneration and necrosis,and mitochondrial structural damage in rats.Renal tubule mitochondrial dynamic protein:Compared with the model group,the expression of division proteins Drp1 and Fis1 was downregulated,the expression of fusion proteins Opa1 and Mfn1 was upregulated,and transmission electron microscopy observed that the mitochondrial fragmentation changes were relatively mild.Apoptosis related indicators and mtDNA copy number of renal tubular cells:Compared with the model group,the content of Bax protein in renal tubular epithelial cells of YSJZG groups increased significantly in cytoplasm(P<0.05)and decreased significantly in mitochondria(P<0.05).The content of CytC protein decreased significantly in cytoplasm(P<0.05)and increased significantly in mitochondria(P<0.05).The copy number of mtDNA increased significantly(P<0.05),and the total levels of SMAC,CytC and Bax mRNA decreased significantly(P<0.05).Correlation between mitochondrial dynamic protein and apoptosis in renal tubular cells:Pearson correlation analysis showed that the expression of Drp1 and Fis1 was negatively correlated with the expression of CytC in mitochondria,and positively correlated with the expression of CytC in cytoplasm.The expression levels of fusion proteins Opa1 and Mfn1 showed a significant positive correlation with CytC expression in mitochondria,and a significant negative correlation with CytC expression in cytoplasm.Conclusion YSJZG can significantly delay the progression of CKD,and its mechanism may be achieved by regulating mitochondrial dynamics of renal tubular epithelial cells,thereby inhibiting endogenous cell apoptosis pathway.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction （半夏泻心汤， BXD） in the treatment of diabetic gastroparesis （DGP）. MethodsA total of 29 SD rats were randomly divided into four groups， blank group （5 rats） and model group， BXD group and metformin group （8 rats in each group）. Except for the blank group， rats were administered intraperitoneally with 1% streptozotocin （STZ） solution and were fed a high-sugar， high-fat diet to establish the DGP rat model. After successful modeling， the BXD group was treated with BXD at 6.68 g/（kg·d） by gavage， the metformin group was treated with metformin hydrochloride at 105 mg/（kg·d） by gavage， and the blank group and the model group were treated with normal saline at 6.68 ml/（kg·d） by gavage， for 8 weeks. After the last administration， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， total cholesterol （TC）， triglycerides （TG） were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin （MTL） and gastrin （GAS）， as well as inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β） and interleukin-10 （IL-10） in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin （HE） staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α （LXRα） levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue， and of janus kinase 2 （JAK2）， phospho-janus kinase 2 （p-JAK2）， signal transducer and activator of transcription 3 （STAT3） and phospho-signal transducer and activator of transcription 3 （p-STAT3） in gastric antrum tissue. Quantitative real-time polymerase chain reaction （qPCR） was used to measure the mRNA expression of LXRα in liver tissue and JAK2， STAT3 in gastric antrum tissue. ResultsCompared with the blank group， the model group showed significant hepatic fatty degeneration， gastric antrum tissue structure destruction， and increases in FBG， HbA1c， TC， and TG levels； the average fluorescence intensity， protein level， and mRNA expression of LXRα in liver tissue were reduced； the gastric emptying rate and gastric tissue GAS and MTL levels decreased； inflammatory factors including TNF-α， IL-6， IL-1β in gastric tissue increased， IL-10 decreased； in gastric antrum tissue， the mRNA expression of p-JAK2/JAK2， p-STAT3/STAT3， and JAK2 and STAT3 increased （P＜0.01）. Compared with the model group， both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology； FBG， HbA1c， TC， and TG levels decreased， while LXRα fluorescence intensity， protein level， and mRNA expression in liver tissue significantly increased； the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher； the levels of TNF-α， IL-6， and IL-1β decreased， whereas IL-10 levels increased， p-JAK2/JAK2， p-STAT3/STAT3， and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased （P＜0.05 or P＜0.01）. The BXD group showed higher level than the metformin group in FBG， HbA1c， and TG levels， lower level in gastric emptying rate and gastric tissue GAS content， and higher level in gastric tissue TNF-α， IL-6， IL-1β levels； there was also a decrease in IL-10 levels， and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue， as well as in p-JAK2/JAK2 levels in gastric antrum tissue （P＜0.05 or P＜0.01）. ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.

ObjectiveThis study aims to reveal the mechanism of liver and kidney injuries caused by Dictamni Cortex and its interrelationship by metabonomics analysis of liver and kidney via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. MethodsThe content of the marker compounds of Dictamni Cortex was measured by high-performance liquid chromatography （HPLC） to carry out quality control. Sprague Dawley （SD） rats were randomly divided into a blank group （normal saline）， an administration group （0.9， 2.7， 8.1 g·kg^-1）， and a high-dose withdrawal control group， with eight rats in each group. Continuous administration was performed once daily for 28 days. The liver and kidney injuries caused by each administration group were assessed by organ indices， pathological observations， and serum and plasma biochemical indices measured by enzyme-linked immunosorbent assay （ELISA）. The potential biomarkers of liver and kidney injuries caused by Dictamni Cortex were screened， and pathway enrichment analysis and correlation analysis were performed based on UPLC-Q-TOF-MS. ResultsCompared with the blank group， both the medium- and low-dose groups showed insignificant damage to the liver and kidney of rats. The high-dose group exhibited the most serious damage， and the level of liver and kidney function indices ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatinine （Cr）， and blood urea nitrogen （BUN）］ and serum inflammatory indices （［interleukin 1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α）］ in the serum were significantly changed （P<0.01）. The liver and kidney metabolism pathways and differential metabolites were quite different. Among them， phenylalanine metabolism， niacin and nicotinamide metabolism， and glycerophospholipid metabolism were common pathways. Correlation analysis of differential metabolites showed that there were significant correlations among disorders of 4′-Phosphopantothenoylcysteine， PC （16∶0/15∶0）， phenylethylamine， arachidonic acid， and linoleic acid in liver and kidney tissue. ConclusionThe decoction of Dictamni Cortex can cause liver and kidney injuries， and its mechanism may be related to oxidative stress and lipid metabolism disorders. The correlation of differential metabolites indicates the interaction between liver and kidney injuries.