ObjectiveTo explore the mechanism by which Yinchenhao Tang intervenes in α-naphthylisothiocyanate （ANIT）-induced cholestatic liver injury by regulating the Takeda G-protein-coupled receptor 5（TGR5）/NOD-like receptor protein 3（NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1） pyroptosis signaling pathway. MethodsForty male Wistar rats were randomly assigned into blank， model， ursodeoxycholic acid， and Yinchenhao Tang groups. Except the blank group， other groups were treated with ANIT dissolved in olive oil for the modeling of cholestatic liver injury. Ursodeoxycholic acid （0.1 g·kg^-1） and Yinchenhao Tang （9.23 g·kg^-1） were administered by gavage. The blank group and the model group were administrated with the same amount of pure water， once a day for 3 days. The blood and liver tissue samples were collected， and the serum levels of liver function indicators were measured by an automatic biochemical analyzer. Hematoxylin-eosin staining was employed to observe the pathological changes of the liver. The levels of interleukin （IL）-1β and IL-18 in the liver tissue were determined by ELISA. The mRNA levels of IL-1β， IL-18， TGR5， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， and GSDMD in the liver tissue were assessed by Real-time PCR. The protein levels of TGR5， NLRP3， ASC， Caspase-1， and GSDMD in the liver tissue were determined by Western blot. ResultsCompared with the blank group， the model group showed elevated levels of alanine amino-transferase （ALT）， aspartate transferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， and total bilirubin （TBil） in the serum （P<0.01）， inflammatory cell infiltration， hepatocyte swelling， and bile duct epithelial cell proliferation in the liver， raised levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA and protein levels of TGR5 （P<0.01）， up-regulated mRNA levels of IL-18 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， and NLRP3 （P<0.05）， and up-regulated protein levels of NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， and GSDMD （P<0.05）. Compared with the model group， the ursodeoxycholic acid group showed declined levels of AST （P<0.01）， TBA （P<0.01）， TBil （P<0.01）， and ALT （P<0.05） in the serum， lowered levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of NLRP3 （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， IL-18 （P<0.05）， and ASC （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.05）， and down-regulated protein levels of NLRP3， ASC， Caspase-1， and GSDMD （P<0.05）. Compared with the model group， the Yinchenhao Tang group showed lowered levels of ALT， AST， ALP， TBA， and TBil in the serum （P<0.01）， declined levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of IL-1β （P<0.01）， NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， and IL-18 （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.01）， and down-regulated protein levels of Caspase-1 and GSDMD （P<0.05）. The liver tissue of the administration groups showed reduced infiltration of inflammatory cells， reduced swelling of hepatocytes， and alleviated proliferation of bile duct epithelial cells. ConclusionYinchenhao Tang can ameliorate ANIT-induced cholestatic liver injury by regulating the hepatocyte pyroptosis mediated by the TGR5/NLRP3/Caspase-1 signaling pathway.

ObjectiveThis study aims to investigate the mechanism of Yinchenhao Tang （YCHT） in regulating macrophage polarization to alleviate cholestatic liver injury，focusing on the TLR4/NF-κB signaling pathway as the entry point. MethodsCholestasis was induced in Wistar rats through a single gavage of 100 mg·kg^-1 α-naphthyl isothiocyanate （ANIT） dissolved in olive oil. The animals were randomly divided into four groups：Model group，YCHT group，ursodeoxycholic acid （UDCA） group （n=10），and a blank group （n=10） that received only 5 mL·kg^-1 olive oil. The YCHT group received 9.23 g·kg^-1·day^-1 of YCHT by gavage，and the UDCA group was treated with 0.1 g·kg^-1·day^-1 of UDCA suspension. Both the normal and model groups were given an equal volume of normal saline，all for three consecutive days. Serum liver function was assessed using an automatic biochemical analyzer. Hematoxylin-eosin （HE） staining was used to observe liver tissue morphology. Levels of tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），transforming growth factor-β （TGF-β），and interleukin-10 （IL-10） were quantified in liver homogenate supernatants via enzyme-linked immunosorbent assay （ELISA）. Western blot analysis measured the relative protein expression of Toll-like receptor 4 （TLR4），nuclear factor-κB （NF-κB），CD206，inducible nitric oxide synthase （iNOS）， CD86，and arginase-1 （Arg-1）. The relative mRNA expression of TLR4/NF-κB，CD206，iNOS，CD86，and Arg-1 in liver tissue was evaluated using real-time quantitative PCR. ResultsCompared with the normal group，the model group exhibited significantly elevated levels of alkaline phosphatase （ALP），total bile acid （TBA），total bilirubin （TBil），aspartate aminotransferase （AST），and alanine aminotransferase （ALT） （P<0.01）. There was a portal area expansion and pronounced inflammatory cell infiltration. The expression of pro-inflammatory markers TNF-α and IL-1β was significantly upregulated （P<0.01），and macrophage markers CD86 and CD206 showed positive expression. Protein and mRNA expressions of iNOS and CD86 were significantly elevated （P<0.01）. The mRNA and protein expressions of the related pathway molecules TLR4 and NF-κB were significantly increased （P<0.01）. Compared with those in the model group， the liver function indicators in the YCHT group showed significant decreases （P<0.05， P<0.01）. The bile duct hyperplasia was significantly alleviated， and the tissue structure became more orderly. The levels of IL-1β and TNF-α were significantly reduced （P<0.01）， while the expression levels of IL-10 and TGF-β significantly increased （P<0.05， P<0.01）. The expression of CD86 significantly decreased （P<0.01）， and the expression of CD206 significantly increased （P<0.01）. The protein and mRNA expressions of iNOS and CD86 significantly decreased （P<0.01）， and those of Arg-1 significantly increased （P<0.01）. The protein and mRNA expressions of CD206 significantly increased （P<0.05， P<0.01）， and the mRNA and protein expressions of related pathway molecules TLR4 and NF-κB significantly decreased （P<0.01）. ConclusionYCHT ameliorates cholestatic liver injury in rats by improving bile metabolism，reducing bile duct dilatation，and mitigating inflammation. These effects are achieved through the inhibition of M1 macrophage activation and the promotion of M2 macrophage polarization，likely via modulation of the TLR4/NF-κB signaling pathway.

Cholestatic liver injury refers to the bile production， secretion， and excretion disorder caused by various reasons. It induces liver injury， metabolic disorders， and dysfunction of the hepatobiliary system， which can further develop into liver fibrosis， cirrhosis， liver failure， and even death. At present， the preferred drug for clinical treatment is ursodeoxycholic acid， which， however， induces adverse reactions and is intolerant in some patients. Yinchenhao Tang is a representative prescription of traditional Chinese medicine for the treatment of jaundice due to Yang jaundice. It has the effects of clearing heat， eliminating dampness， and removing jaundice and has shown good therapeutic effect in long-term clinical application. Modern pharmacological studies have found that this prescription has anti-inflammatory， anti-oxidation， bile acid balance-regulating， hepatocyte apoptosis-inhibiting and other liver-protecting effects. This paper reviews the relevant clinical and animal experimental studies on Yinchenhao Tang in the treatment of cholestatic liver injury in recent years. Yinchenhao Tang can intervene in the progression of cholestatic liver injury by regulating bile acid metabolism and excretion， reducing inflammatory response， inhibiting oxidative stress， alleviating endoplasmic reticulum stress， inhibiting hepatocyte apoptosis， and protecting intestinal mucosal barrier. This paper systematically expounds the molecular mechanisms by which Yinchenhao Tang regulates cholestatic liver injury that are confirmed by current research， aiming to provide reference for the clinical application and in-depth study of Yinchenhao Tang.

ObjectiveStarting from the etiology， pathogenesis， and treatment strategies of endometriosis and adenomyosis， to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology. MethodsAccording to the systematic review of text and opinion （SrTO） process developed by the Joanna Briggs Institute （JBI） in Australia， this paper determined literature screening criteria by searching China National Knowledge Infrastructure （CNKI）， VIP， Wanfang， and China Biomedical Literature Database. Information was extracted after literature screening， and quality evaluation was conducted using the JBI Narrative， Text， and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative， Opinion， Text Evaluation， and Review Tool Summary Table was used for information synthesis， and data analysis and display were conducted in the form of text and charts. ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics， meridian circulation location， pathological product evolution， disease duration， emotional psychology， lifestyle habits， preference for food and drink， innate endowment， and acquired injury. In terms of treatment， it was advocated to divide the stage， treat according to different types， adapt to the times， integrate nature and humans， and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects， make good use of classic formulas and small prescriptions， pay attention to protecting the spleen and stomach and regulating emotions， and make good use of self-formulated empirical formulas for internal or external use. Besides， individualized long-term management of patients was also advocated. ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes， mechanisms， diagnosis， and treatments of endometriosis， providing a scientific and standardized reference for future theoretical exploration.

Objective:To explore the effect and mechanism of Chlorfortunone A(ChlA) in the treatment of diabetic nephropathy(DN) in mice.Methods:The DN model mice were assigned to DN, low-dose ChlA(ChlAL) and high-dose ChlA(ChlAH), and the normal control groups(Ctrl). Kidney tissue was analyzed via HE and Masson staining, and urine albumin, fasting blood glucose and kidney weight were measured. Collagen1 and α-SMA proteins were detected in renal tissues. The level of GSH-px, SOD, CAT, and TGF-β were detected. The TGF-β/Smad2 pathway in kidney tissue was detected. The mechanism was verified by setting the high glucose+ ChlA+ TGF-β group in MPC-5 cells. The proliferation of the cells and DCFDA staining were detected.Results:Compared to the Ctrl group, the DN group had significantly higher UACR and kidney weight( P<0.001). High-dose ChlA reduced UACR and kidney weight( P<0.05), with no effect on blood glucose( P>0.05). Masson staining showed reduced fibrosis with ChlA treatment. Collagen I and α-SMA expressions were significantly higher in DN( P<0.001) and decreased with ChlA treatment( P<0.05). GSH-px, SOD, and CAT levels were lower in DN( P<0.001), while TGF-β was elevated( P<0.001); ChlA increased antioxidant enzymes and decreased TGF-β( P<0.05). The TGF-β/Smad2 pathway was upregulated in DN( P<0.001) and inhibited by ChlA( P<0.001). In vitro, ChlA reduced cell proliferation( P<0.05) and increased ROS levels( P<0.001). Conclusions:ChlA alleviates kidney injury and fibrosis in DN mice, reduces oxidative stress, which may be related to the inhibition of the TGF-β/Smad2 pathway.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Colorectal cancer (CRC) is one of the common gastrointestinal tumors, and radiotherapy is an important treatment modality for CRC. Increased radioresistance in tumors can lead to recurrence and poor prognosis. MicroRNAs (miRNAs) are naturally occurring small non-coding RNAs whose expression patterns are associated with clinical variables such as tumor type and stage, exhibiting significant oncogenic or tumor-suppressive functions. miRNAs regulate tumor biological functions, such as proliferation, apoptosis, invasion/metastasis, and angiogenesis, at the post-transcriptional level, either directly or indirectly. Radiotherapy, which utilizes ionizing radiation (IR) to induce DNA damage, is a molecular event mainly involving the activation of intracellular signaling pathways and post-translational modification of proteins. Mutiple studies have demonstrated that miRNAs can counteract radioresistance in CRC by regulating IR-induced DNA damage, programmed cell death, exosomes, and the generation of tumor stem cells, potentially optimizing CRC treatment. This review summarizes the research progress on the role of miRNAs in radiosensitivity in CRC, aiming to provide new therapeutic insights and approaches for CRC patients.

Objective To explore the prognostic value of combined serum oxidized low-density lipoprotein(ox-LDL),remnant cholesterol(RC)and neutrophil-to-lymphocyte ratio(NLR)tests for clinical prognosis in patients with intracranial atherosclerotic stenosis(ICAS).Methods Patients with acute cerebral infarction were admitted to Cangzhou Central Hospital from June 2022 to December 2023 and diagnosed with ICAS by head MRI.A clinical diagnosis was selected(observation group,n=160).According to the modified Rankin scale(mRS)score,they were separated into a good prognosis group(mRS 0～2 points,n=52)and a poor prognosis group(mRS≥3 points,n=108).160 healthy volunteers who underwent physical examinations were used as a reference group.Magnetic particle immunochromatography was applied to detect serum ox-LDL levels.Clinical data of patients were collected,and the levels of RC and NLR were calculated.The Spearman method was used to analyze the correlation between serum ox-LDL,RC,NLR levels and mRS scores.Logistic regression was applied to analyze the factors influencing prognosis in ICAS patients.Receiver operating characteristic curve(ROC)was used to analyze the predictive value of serum ox-LDL,RC and NLR levels for the prognosis of ICAS patients.Results Compared with reference group,the serum levels of ox-LDL(53.65±8.35 U/L vs 33.23±6.42 U/L),RC(0.82±0.15 mmol/L vs 0.52±0.13 mmol/L)and NLR(2.84±0.38 vs 1.95±0.26)in observation group were obviously increased,and the differences were statistically significant(t=24.523,65.079,62.911,all P<0.05).The serum levels of ox-LDL(57.52±8.72 U/L),RC(0.84±0.14 mmol/L)and NLR(3.02±0.45)in the poor prognosis group were higher than those in the good prognosis group(45.62±6.63 U/L,0.79±0.12 mmol/L,2.48±0.36),and the differences were statistically significant(t=8.699,8.507,7.562,all P＜0.05),and there were differences in TC,LDL-C,HDL-C levels and mRS scores between the two groups,and the differences were statistically significant(t=15.755～27.072,all P<0.05).The serum levels of ox-LDL,RC,NLR were positively correlated with mRS scores(r=0.612,0.623,0.653,all P<0.05).The levels of TC,LDL-C,HDL-C,ox-LDL,RC and NLR were all factors that affected the prognosis of ICAS(all P<0.05).The AUC of serum ox-LDL,RC and NLR for predicting prognosis in ICAS patients were 0.894(0.835～0.937),0.860(0.797～0.910)and 0.817(0.748～0.874),respectively.The combined AUC(95%CI)of the three was 0.965(0.923～0.987),the combination of the three was more valuable than predicting serum ox-LDL,RC and NLR alone(Z=3.030,3.969,4.839,all P<0.05).Conclusion The serum levels of ox-LDL,RC and NLR in ICAS patients have all increased and are positively correlated with mRs scores.The three have predictive value for the prognosis of ICAS patients,and the combined detection of the three has higher clinical value.

Objective:To explore the impacts of carnosic acid(CA)on learning and cognitive function in epileptic rats and the mechanism of regulating PKA-CREB signaling pathway in this process.Methods:Epilepsy rat models were prepared by intraperi-toneal injection of 50 mg/kg PTZ.After successful modeling,the rats were randomly grouped into control group,model group,CA low-dose group,CA high-dose group,CA high+PKA inhibitor group(CA high+H-89 group),with 15 rats in each group.The epileptic be-havior of rats in each group was evaluated;Morris water maze experiment was applied to test the cognitive ability of rats;HE staining and Nissl staining were applied to detect the morphology of hippocampal tissue and neurons of rats in each group;ELISA was applied to detect the contents of IL-1β,TNF-α,MDA,and the SOD activity in the hippocampus of rats in each group;and Western blot was applied to detect the protein expressions of PKA,p-PKA,CREB,p-CREB and BDNF in the hippocampus of rats in each group.Results:Compared with control group,the hippocampal neurons of rats in model group were irregularly arranged,with pyknosis of the nuclei,and the number of neurons decreased,the epilepsy frequency,Racine grading,escape latency,time of first platform crossing,and levels of IL-1β,TNF-α and MDA all increased,the frequency of crossing the platform,SOD activity,p-PKA/PKA,p-CREB/CREB,and the expression of BDNF protein all reduced(P<0.05);compared with model group,the arrangement of neuronal cells in hippocampal tissue of rats in CA group gradually became orderly,nuclear pyknosis gradually decreased,and the number of neurons increased,the epilepsy frequency,Racine grading,escape latency,time of first platform crossing,and levels of IL-1β,TNF-α and MDA all reduced,the frequency of crossing the platform,SOD activity,p-PKA/PKA,p-CREB/CREB,and the expression of BDNF protein all increased(P<0.05);further injection of PKA inhibitors on the basis of high-dose CA treatment showed that the improvement effects of high-dose CA on cognitive dysfunction,neuronal damage,inflammation,and oxidative stress in epileptic rats were reversed(P<0.05).Conclusion:CA can improve the learning and cognitive function of epileptic rats by activating the PKA-CREB signaling pathway.