ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

ObjectiveTo dynamically observe and evaluate the damage to the pulmonary air-blood barrier in mice during the inflammatory cancer transformation process of ulcerative colitis （UC） based on the "lung-intestine correlation" theory. MethodsSixty-five C57BL/6 mice were divided into a normal group （n=25） and a model group （n=40） using a random number table. Azoxymethane/dextran sodium sulfate （DSS） method was used to establish a mouse model of UC inflammation cancer transformation in the modeling group. According to the tissue collection time points at 5， 8， 11， 13， and 15 weeks， the normal group mice were randomly divided into the normal 5w， 8w， 11w， 13w， and 15w groups. The model group mice， 10 mice of which died after the first cycle of DSS administration， were randomly divided into model 5w， 8w， 11w， 13w， and 15w groups. During the experiment， the general condition of the mice was observed daily， and their body weight was measured weekly. At the corresponding tissue collection time points， the colon length of each group was measured. Histopathology of mouse lung and colon tissues was examined using HE staining. Immunofluorescence was used to detect changes in the positive expression of tight junction protein （ZO-1）， vascular endothelial cadherin （VE-cadherin）， and cytoskeletal protein （F-actin） in lung and colon tissues. RT-PCR was used to detect the mRNA expression of apoptosis regulatory proteins B-cell lymphoma-2 （Bcl-2）， BCL2-associated X protein （Bax）， and Cysteine aspartic acid protease-3 （Caspase-3） in lung tissues. Western Blot was employed to measure protein levels of ZO-1， VE-cadherin， and F-actin in lung tissues. ResultsCompared to the normal group at the same time point， the mice in the model group at each time point generally had poorer conditions， with weight loss and shortened colon length （P＜0.05 or P＜0.01）. In the model 5w group， there was significant inflammatory cell infiltration in the colon tissue； in the model 8w group， there was mild atypical hyperplasia； in the model 11w group， the crypt structure was disordered， and moderate to severe atypical hyperplasia occurred； in the model 13w and 15w groups， tumors appeared. Pulmonary interstitial lesions， inflammation， vasculitis， and fibrosis were observed at all stages of UC inflammation cancer transformation. The protein levels of ZO-1， VE-cadherin， and F-actin， as well as Bcl-2 mRNA expression in lung tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period， while the expressions of Bax and Caspase-3 mRNA increased； the expressions of ZO-1， VE-cadherin， and F-actin proteins in colon tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period （P＜0.01 or P＜0.05）. Compared to the model 5w group， the ZO-1 and F-actin protein levels and Bcl-2 mRNA expression in lung tissue in the other model groups increased in the atypical hyperplasia period and canceration period， while the expressions of Bax and Caspase-3 mRNA decreased； the expression of ZO-1 protein in colon tissue increased in the canceration period， and the expression of VE-cadherin protein decreased in the atypical hyperplasia period （P＜0.01 or P＜0.05）. ConclusionIn the process of "inflammatory response-atypical hyperplasia-carcinogenesis" in UC inflammatory cancer transformation mice， there were damage to air-blood barrier.

ObjectiveThis study aims to explore the effect of Feiyanning granules on ferroptosis in lung cancer cells and its regulatory function within the nuclear transcription factor E₂-related factor 2 （Nrf2）/mouse solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe cell counting kit-8 （CCK-8） method was used to detect the effect of Feiyanning granule on the proliferation of A549 lung cancer cells. A549 lung cancer cells were categorized into a blank group， a ferroptosis inhibitor-1 （Fer-1） group （10 μmol·L^-1）， a Feiyanning granules （600 mg·L^-1） group， and a Feiyanning granules + Fer-1 group. After 48 hours of intervention， the activity and morphology of the cells were observed. The CCK-8 method was employed to measure cell viability. Biochemical assays were carried out to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ions （Fe²⁺） in A549 cells. Western blot was utilized to evaluate the expression levels of Kelch-like ECH-associated protein 1 （Keap1）， Nrf2， SLC7A11， and GPX4 proteins. A549 lung cancer cells were categorized into a blank group and a Feiyanning Granule group （600 mg·L^-1）， and mitochondrial morphology was examined via transmission electron microscopy （TEM）. ResultsAfter the intervention of Feiyaning granules， the proliferation of A549 cells was significantly inhibited in a concentration-dependent manner compared with that in the blank group （P<0.01）. Compared with the blank group， the Feiyanning granules group exerted an significantly inhibitory effect on the viability of lung cancer cells （P<0.01）. Compared with that in the Feiyanning granules group， the cell viability in the Feiyanning granules +Fer-1 group was obviously restored （P<0.05）. Compared with the blank group， the Feiyanning Granule group showed a significant increase in the levels of ROS， MDA， and Fe²⁺ （P<0.01）， a significant decrease in the GSH level （P<0.01）， and facilitated ferroptosis. Compared with the blank group， the Feiyanning granules group showed significantly decreased expression of Nrf2， SLC7A11， and GPX4 proteins and enhanced expression of Keap1 （P<0.01）. Compared with those in the Feiyanning Granule group， the protein levels of Nrf2， SLC7A11， and GPX4 increased significantly （P<0.01）， and the expression of Keap1 decreased significantly in the Feiyanning granules + Fer-1 group （P<0.01）. Compared with the blank group， the Feiyaning granules group exhibited reduced mitochondrial size and increased matrix electron density. ConclusionFeiyanning granules can induce ferroptosis in lung cancer cells， and its underlying mechanism might be associated with the inhibition of the Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

Perimenopausal depression （PMD） is an affective disorder that occurs in women during the transition from sexual maturity to old age. It can induce various complications， such as insomnia and cognitive decline. The etiology of PMD is complex. Although multiple hypotheses have been proposed， there is still no unified theory that fully explains its pathogenesis. Research into its mechanisms relies heavily on animal experiments， and establishing reliable animal models is crucial for experimental studies. Appropriate animal models can better simulate human pathophysiological states， rapidly evaluate the efficacy and safety of drugs and intervention methods， grasp the essence of the disease， and uncover its intrinsic connections， thereby exploring more advanced intervention strategies. However， there is a lack of systematic review and summarization of literature related to model construction. Additionally， traditional Chinese medicine （TCM）， adhering to the principles of ''syndrome differentiation and treatment'' and ''holistic concept''， has shown significant efficacy in treating PMD. In recent years， research exploring and analyzing its therapeutic mechanisms has been increasing. Therefore， to gain a clearer and more comprehensive understanding of PMD animal modeling methods and the mechanisms of TCM， this paper reviewed Chinese and English literature on PMD animal models and mechanisms of TCM in PMD treatment. It summarized the construction methods of single-factor and multi-factor PMD models， and discussed the advantages and disadvantages of each modeling approach. Furthermore， it delved into the mechanisms of TCM intervention in PMD， revealing that TCM formulas primarily exert their effects by regulating the hypothalamic-pituitary-adrenal axis， hypothalamic-pituitary-ovarian axis， gut-brain axis， cell signaling pathways， neural circuits， hormone levels， and neurotransmitter levels. This review aims to provide a reference for future research in this field. In summary， by summarizing the progress in the methods for PMD animal model construction and the mechanisms of TCM， the paper seeks to offer new insights into the mechanistic research of TCM intervention in PMD.

OBJECTIVE T o explore the action mechanisms of Ganghuo Qingwen granules(GHQWG)in treatment of influenza based on network pharmacology and molecular docking technique.METHODS The TCMSP database was logged in to search for active compounds,targets of GHQWG and targets of influenza so as to screen out the intersected targets between HGQWG and influenza and establish a drug-ingredient-target network.The poten-tial mechanisms were analyzed by means of protein-protein interaction analysis,Gene Ontology(GO)function an-notation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the activity of binding the key targets with ingredients was validated by molecular docking.RESULTS GHQWG contained 90 types of po-tential active ingredients,312 active ingredient targets,1996 influenza targets and 134 intersection targets.The core ingredients included quercetin,kaempferol and luteolin;the key targets involved V-Rel reticuloendotheliosis viral oncogene homolog A(RELA),tumor protein 53(TP53),mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),serine/threonine kinase proteins 1(AKT1)and mitogen-activated protein kinase 1(MAPK1).The function enrichment showed that GHQWG could regulate the processes of gene expression,in-flammatory reaction and apoptosis.The result of KEGG indicated that GHQWG played therapeutic effect on influ-enza mainly through C type agglutinin receptor,TNF and in terleukin-17(IL-17)signaling pathway.The molecu-lar docking analysis showed that RELA,TP53,M APK3,TNF,AKT1 and M APK1 had strong activities of bind-ing with quercetin,kaempferol,luteolin,β-sitosterol,wogonin,stigmasterol,caffeic acid and isorhamnetin.CONCLUSION GHQWG may regulate the key targets of signaling pathways of C type agglutinin receptor,TNF and IL-17 through multiple ingredients-multiple targes-multiple pathway mechanisms so as to play the therapeutic effect on influenza.

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.

Aim To investigate the mechanism by which Aiweixin oral liquid(AWX)alleviates myocar-dial ischemia-reperfusion injury in rats through the reg-ulation of mitochondrial fusion and fission.Methods Seventy-two healthy male Sprague-Dawley rats were randomly assigned to six groups(n=12)using a ran-dom number table:sham surgery group,model group,low-dose AWX(1 mL·kg-1)group,medium-dose AWX(2 mL·kg-1)group,high-dose AWX(4 mL·kg-1)group,and positive control drug trimetazidine(10 mg·kg-1)group.A myocardial ischemia-reper-fusion injury(MIRI)model was established by ligating the left anterior descending coronary artery of the rat heart,followed by 30 minutes of ischemia and 90 mi-nutes of reperfusion.In the sham surgery group,only a suture was placed without ligation.The rats in the treatment groups were pre-gavaged with AWX starting 10 days prior to the modeling procedure.Lead Ⅱ elec-trocardiograms were recorded before and after reperfu-sion in each group to observe the changes in electrocar-diographic parameters.The myocardial infarct size in each group was assessed using TTC staining.The his-topathological changes in myocardial tissue were exam-ined under a light microscope using hematoxylin and eosin(HE)staining.The serum levels of adenosine triphosphate(ATP)and cardiac troponin I(cTnI)were measured using enzyme-linked immunosorbent as-say(ELISA).Superoxide dismutase(SOD)activity and the levels of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were determined using bio-chemical assay kits.The protein expression levels of dynamin-related protein 1(dynamin-relatedprotein 1,DRP1),mitochondrial fission factor(mitochondrial fis-sion factor,MFF),mitochondrial fission protein 1(mi-tochondrial fission protein 1,FIS1),mitofusin 1(mito-fusion-1,MFN1),and mitofusin 2(mitofusion-2,MFN2)were evaluated by Western blot analysis.Re-sults Compared with the sham group,the model group exhibited aggravated myocardial tissue pathological damage,an increased percentage of myocardial infarct size,decreased serum SOD activity and ATP levels,and significantly elevated levels of MDA,cTnI,and LDH activity.Additionally,the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1 was up-regulated,while the expression of fusion-related factors MFN1 and MFN2 was downregulated.Compared with the model group,Aiweixin oral liquid significantly alle-viated myocardial injury,reduced the percentage of my-ocardial infarct size,increased serum SOD activity and ATP levels,decreased MDA content and cTnI and LDH activity,downregulated the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1,and up-regulated the protein expression of fusion-related factors MFN1 and MFN2.Conclusion Aiweixin oral liquid alleviates myocardial ischemia-reperfusion injury in rats by regulating abnormal mitochondrial fusion and fis-sion.

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.

Aim To investigate the mechanism by which Aiweixin oral liquid(AWX)alleviates myocar-dial ischemia-reperfusion injury in rats through the reg-ulation of mitochondrial fusion and fission.Methods Seventy-two healthy male Sprague-Dawley rats were randomly assigned to six groups(n=12)using a ran-dom number table:sham surgery group,model group,low-dose AWX(1 mL·kg-1)group,medium-dose AWX(2 mL·kg-1)group,high-dose AWX(4 mL·kg-1)group,and positive control drug trimetazidine(10 mg·kg-1)group.A myocardial ischemia-reper-fusion injury(MIRI)model was established by ligating the left anterior descending coronary artery of the rat heart,followed by 30 minutes of ischemia and 90 mi-nutes of reperfusion.In the sham surgery group,only a suture was placed without ligation.The rats in the treatment groups were pre-gavaged with AWX starting 10 days prior to the modeling procedure.Lead Ⅱ elec-trocardiograms were recorded before and after reperfu-sion in each group to observe the changes in electrocar-diographic parameters.The myocardial infarct size in each group was assessed using TTC staining.The his-topathological changes in myocardial tissue were exam-ined under a light microscope using hematoxylin and eosin(HE)staining.The serum levels of adenosine triphosphate(ATP)and cardiac troponin I(cTnI)were measured using enzyme-linked immunosorbent as-say(ELISA).Superoxide dismutase(SOD)activity and the levels of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were determined using bio-chemical assay kits.The protein expression levels of dynamin-related protein 1(dynamin-relatedprotein 1,DRP1),mitochondrial fission factor(mitochondrial fis-sion factor,MFF),mitochondrial fission protein 1(mi-tochondrial fission protein 1,FIS1),mitofusin 1(mito-fusion-1,MFN1),and mitofusin 2(mitofusion-2,MFN2)were evaluated by Western blot analysis.Re-sults Compared with the sham group,the model group exhibited aggravated myocardial tissue pathological damage,an increased percentage of myocardial infarct size,decreased serum SOD activity and ATP levels,and significantly elevated levels of MDA,cTnI,and LDH activity.Additionally,the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1 was up-regulated,while the expression of fusion-related factors MFN1 and MFN2 was downregulated.Compared with the model group,Aiweixin oral liquid significantly alle-viated myocardial injury,reduced the percentage of my-ocardial infarct size,increased serum SOD activity and ATP levels,decreased MDA content and cTnI and LDH activity,downregulated the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1,and up-regulated the protein expression of fusion-related factors MFN1 and MFN2.Conclusion Aiweixin oral liquid alleviates myocardial ischemia-reperfusion injury in rats by regulating abnormal mitochondrial fusion and fis-sion.