AIM:To investigate the effects of Xiaoyao-Kang'ai-Jieyu formula(XYKAJY)-containing serum on the co-culture of BV2 and HT22 cells from mice with breast cancer-related depression(BCRD).METHODS:The op-timal concentration of XYKAJY-containing serum was determined using mouse HT22 cells.In vitro co-culture model of mouse HT22 and BV2 cells was established through incubation with 4T1 cell supernatant and 200 μmol/L corticosterone.The cells were then divided into control group,model group,blank serum group,positive drug serum group,5%XY-KAJY-containing serum group,10%XYKAJY-containing serum group,15%XYKAJY-containing serum group and 20%XYKAJY-containing serum group.Alterations in HT22 cell viability was detected by CCK8 assay.The concentration level of interleukin-1β(IL-1β),IL-6 and IL-18 in the cell supernatant was quantified using enzyme-linked immunosorbent as-say(ELISA).Flow cytometry was conducted to assess the apoptosis rate of HT22 cells and quantify the expression levels of adhesion molecule CD11b on the surface of BV2 cells.Immunofluorescence was performed to determine the expression of neuron-specific enolase(NSE),synapsin 1(Syn1)and postsynaptic density protein 95(PSD95)in HT22 cells,and that of inducible nitric oxide synthase(iNOS)in BV2 cells.RESULTS:Treatment with XYKAJY-containing serum down-regulated CD11b expression level in BV2 cells(P<0.01),and reduced the release of IL-1β,IL-6 and IL-18(P<0.01).Moreover,it significantly improved the viability of HT22 cells(P<0.01),enhanced cell morphology integrity,and reduced the apoptosis rate(P<0.01).CONCLUSION:These findings indicated that XYKAJY-containing serum im-proved the function of mouse HT22 neurons by regulating the polarization phenotype of mouse BV2 cells and alleviating neuroinflammatory-induced toxicity.

Anxiety disorder is a common emotional disorder,with its pathological mechanisms involving the imbalance of multiple neurotransmitter systems,especially the dysfunction of the gamma-aminobutyric acid(GABA)system.This article explored the TCM understanding of anxiety disorder,and summarized and organized the research on the regulation of GABA system in the treatment of anxiety disorders through TCM monomers and formulas from the aspects of terpenes,flavonoids,phenolic acids,lignans,cinnamic acids,saponins,etc.At present,the research mainly involved chrysin,baicalin,ginsenoside,Baihe Dihuang Decoction,Bentun Decoction,Suanzaoren Decoction,Chaihu Jia Longgu Muli Decoction,etc.The mechanism involved regulating the inflammatory response of the body,alleviating oxidative stress damage,restoring the hyperactive HPA axis and other action pathways,which could provide a reference for the related research of TCM anti anxiety treatment and the development of new drugs.

Depression is a mental disease with in-creasing prevalence worldwide,which seriously en-dangers human health with high disability rate and high suicide rate.Epigenetics is an emerging genet-ic theory in the 21st century.Its main research con-tent is to regulate the process of gene transcription or translation and affect its function and character-istics without changing the DNA sequence.These include DNA methylation,histone modification,chromatin remodeling and non-coding RNA regula-tion.The nervous system is susceptible to changes in the activity of epigenetic modifiers,and an in-creasing number of studies have shown that genet-ics and environment play an important role in the development of depression.This review will focus on the epigenetic mechanisms of depression.

Depression is a mental disease with in-creasing prevalence worldwide,which seriously en-dangers human health with high disability rate and high suicide rate.Epigenetics is an emerging genet-ic theory in the 21st century.Its main research con-tent is to regulate the process of gene transcription or translation and affect its function and character-istics without changing the DNA sequence.These include DNA methylation,histone modification,chromatin remodeling and non-coding RNA regula-tion.The nervous system is susceptible to changes in the activity of epigenetic modifiers,and an in-creasing number of studies have shown that genet-ics and environment play an important role in the development of depression.This review will focus on the epigenetic mechanisms of depression.

Anxiety disorder is a common emotional disorder,with its pathological mechanisms involving the imbalance of multiple neurotransmitter systems,especially the dysfunction of the gamma-aminobutyric acid(GABA)system.This article explored the TCM understanding of anxiety disorder,and summarized and organized the research on the regulation of GABA system in the treatment of anxiety disorders through TCM monomers and formulas from the aspects of terpenes,flavonoids,phenolic acids,lignans,cinnamic acids,saponins,etc.At present,the research mainly involved chrysin,baicalin,ginsenoside,Baihe Dihuang Decoction,Bentun Decoction,Suanzaoren Decoction,Chaihu Jia Longgu Muli Decoction,etc.The mechanism involved regulating the inflammatory response of the body,alleviating oxidative stress damage,restoring the hyperactive HPA axis and other action pathways,which could provide a reference for the related research of TCM anti anxiety treatment and the development of new drugs.

AIM:To investigate the effects of Xiaoyao-Kang'ai-Jieyu formula(XYKAJY)-containing serum on the co-culture of BV2 and HT22 cells from mice with breast cancer-related depression(BCRD).METHODS:The op-timal concentration of XYKAJY-containing serum was determined using mouse HT22 cells.In vitro co-culture model of mouse HT22 and BV2 cells was established through incubation with 4T1 cell supernatant and 200 μmol/L corticosterone.The cells were then divided into control group,model group,blank serum group,positive drug serum group,5%XY-KAJY-containing serum group,10%XYKAJY-containing serum group,15%XYKAJY-containing serum group and 20%XYKAJY-containing serum group.Alterations in HT22 cell viability was detected by CCK8 assay.The concentration level of interleukin-1β(IL-1β),IL-6 and IL-18 in the cell supernatant was quantified using enzyme-linked immunosorbent as-say(ELISA).Flow cytometry was conducted to assess the apoptosis rate of HT22 cells and quantify the expression levels of adhesion molecule CD11b on the surface of BV2 cells.Immunofluorescence was performed to determine the expression of neuron-specific enolase(NSE),synapsin 1(Syn1)and postsynaptic density protein 95(PSD95)in HT22 cells,and that of inducible nitric oxide synthase(iNOS)in BV2 cells.RESULTS:Treatment with XYKAJY-containing serum down-regulated CD11b expression level in BV2 cells(P<0.01),and reduced the release of IL-1β,IL-6 and IL-18(P<0.01).Moreover,it significantly improved the viability of HT22 cells(P<0.01),enhanced cell morphology integrity,and reduced the apoptosis rate(P<0.01).CONCLUSION:These findings indicated that XYKAJY-containing serum im-proved the function of mouse HT22 neurons by regulating the polarization phenotype of mouse BV2 cells and alleviating neuroinflammatory-induced toxicity.

Objective To explore the effect and related mechanism of Zuogui Jiangtang Jieyu Prescription on neuroinflammation of nucleus accumbens in rats with diabetes mellitus(DM)complicated with depression based on dopamine receptor.Methods DM,depression and DM complicated with depression models were respectively established through a combination of high-fat feeding and streptozotocin intraperitoneal injection,as well as chronic unpredictable mild stress+solitary cage feeding.The rats were divided into control group,depression group,DM group,DM complicated with depression group,positive group,D1R agonists group,D2/3R agonists group and Zuogui Jiangtang Jieyu Prescription group.Depression and learning and memory abilities in rats were assessed using open field experiments,forced swimming experiments and water maze experiments.Neuronal damage in nucleus accumbens was detected through HE and Nissl staining.Serum contents of 5-hydroxytryptamine(5-HT),dopamine(DA),interleukin(IL)-1β and IL-18 were detected by ELISA.The expressions of D1R,D2R,D3R and Iba1/NLRP3 in nucleus accumbens were detected by immunofluorescence.The protein expressions of D1R,D2R,D3R,NLRP3,ASC,Caspase-1 p20 and IL-1β in nucleus accumbens were detected by Western blot.Results Compared with the control group,the changes of fasting blood glucose(FBG)in rats of DM complicated with depression group significantly increased(P<0.01),the total distance and number of activities in the open field experiment,the time ratio of staying in the original platform quadrant and the number of times crossed the original platform in the water maze experiment significantly decreased(P<0.05,P<0.01),the forced swimming immobility time and the escape latency period in the water maze experiment were prolonged(P<0.05,P<0.01),the contents of serum 5-HT and DA significantly decreased(P<0.01),the contents of IL-1β and IL-18 significantly increased(P<0.05,P<0.01),neurons in the nucleus accumbens showed nuclear condensation,degeneration,and increased necrotic cells,with loss of Nissl bodies,the expressions of D1R,D2R and D3R were significantly decreased(P<0.01),while the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein significantly increased(P<0.05,P<0.01).Compared with the DM complicated with depression group,the changes of FBG significantly decreased in the Zuogui Jiangtang Jieyu Prescription group,learning and memory abilities were enhanced,depression-like behavior was improved,and the damage to neurons in the nucleus accumbens was reduced,the contents of serum 5-HT and DA significantly increased(P<0.01),the contents of IL-1β and IL-18 significantly decreased(P<0.01),the expressions of D1R,D2R and D3R in the nucleus accumbens increased(P<0.05,P<0.01),and the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein decreased(P<0.05,P<0.01).Conclusion The dopaminergic system dysfunction and neuroinflammation are the key mechanisms of DM complicated with depression.Zuogui Jiangtang Jieyu Prescription may improve neuroinflammation by regulating the dopamine receptor to inhibit the activation of microglial NLRP3 signaling in the nucleus accumbens.

Diabetic kidney disease （DKD） is a common complication of diabetes and a leading cause of end-stage kidney disease. Its pathogenesis is complex， and it presents a significant challenge in treatment， gradually becoming a major global public health issue. One of the main pathological changes in DKD is tubulointerstitial fibrosis， clinically characterized by proteinuria and declining kidney function， which severely impacts the daily life of patients. Currently， western medicine commonly uses methods such as controlling blood sugar and blood pressure， and reducing proteinuria to treat DKD， but the efficacy is unsatisfactory， and there are many side effects. As reported， traditional Chinese medicine （TCM） treatment for DKD has many advantages， such as low cost， significant efficacy， and minimal adverse reactions. More researchers focusing on DKD are turning their attention to TCM， and progress has been made in related studies both in China and abroad. The Wnt/β-catenin signaling pathway is relatively evolutionarily conserved and plays a crucial role in normal biological development and the entire life process. Studies have demonstrated that abnormal activation of the Wnt/β-catenin signaling pathway is related to renal fibrosis， which coincides with TCM theory of "collateral diseases". By reviewing relevant literature， this article reviewed the Wnt/β-catenin signaling pathway and its role in DKD and summarized the research status of TCM monomers， single drug extracts， and TCM formulas in improving renal fibrosis and treating DKD through the improvement of glomerular mesangial cells， renal tubular epithelial cells， and podocyte injury， aiming to provide new ideas and directions for TCM treatment of DKD.

OBJECTIVE To evaluate the intervention effect of Caulis sinomenii compatible with prepared Aconiti Lateralis on bone destruction in rheumatoid arthritis （RA）model rats ，and to investigate its mechanism. METHODS Totally 40 SD rats were randomly divided into blank group ，model group ，positive control group （indomethacin 0.013 5 g/kg）and C. sinomenii compatible with prepared Aconiti Lateralis group （C. sinomenii 1.08 g/kg+prepared Aconiti Lateralis 1.35 g/kg）according to body mass ，with 10 rats in each group. Except for the blank group ，all the other groups made RA rat models by injecting type Ⅱ bovine collagen. Rats in each group were given corresponding drugs or distilled water intragastrically. The general information ，body weight ，foot swelling and arthritis index （AI）scores of rats in each group were recorded. After the 30th day of administration ，the changes of ankle bone in rats were detected by small animal CT machine. The levels of inflammatory factors [interleukin- 31（IL-31），IL-25 and IL- 3] and chemokines [receptor activator of nuclear factor κB ligand（RANKL），receptor activator of nuclear factor κB （RANK）and osteoprotegerin （OPG）] in serum were detected by enzyme-linked immunosorbent assay. Pathological indexes of rat ankle joint were observed by HE staining. Immunohistochemical method was used to detect the expression of RANKL ，RANK and OPG in synovial tissue of rat ankle joint. RESULTS Compared with blank group ，the mental state of the model group was weak ， the activity decreased significantly ，the hair lost luster ，and the body weight decreased significantly on the 12th to 30th days （P＜ 0.05 or P＜0.01）；the swelling degree of the foot was significantly increased and the AI score was significantly increased on the 12th to 30th days（P＜0.01）；the ankle joint in model group had rough surface ，obvious tissue damage and serious bone erosion ； serum levels of IL- 31，IL-25，IL-3，RANKL and RANK were increased significantly ，while the level of OPG was decreased significantly （P＜0.01）； the expression of RANKL and RANK in synovium of ankle joint increased significantly ， while the expression of OPG decreased significantly （P＜0.01）. Compared with model group ，the above indexes of administration groups were improved to varying degrees ，and most of the differences were statistically significant （P＜0.05 or P＜0.01）. CONCLUSIONS By inhibiting the RANKL/RANK/OPG signaling pathway ，C. sinomenii compatible with prepared Aconiti Lateralis can inhibit the excessive proliferation of osteoclasts and restore the balance of bone metabolism so as to play a role in protecting bone joints and treating RA.

Objective To investigate the efficacy and mechanism of action of Compound Chaijin Jieyu Tablets (复方柴金解郁片, CCJJYT) in rats with insomnia complicated with depression. Methods Seventy-two Sprague-Dawley rats were randomly assigned into eight groups: the control, chronic unpredictable mild stress (CUMS), sleep deprivation (SD), CUMS + SD, positive drug (venlafaxine hydrochloride + diazepam), CCJJYT high-dose (CCJJYT˗2×), medium-dose (CCJJYT˗1×), and low-dose (CCJJYT˗0.5×) groups, with nine rats in each group. Depression-like behavior was evaluated by body weight, food intake, and behavioral tests such as the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and pentobarbital-induced sleep test (PST). Hematoxylin-eosin (HE) staining and Golgi-Cox staining were used to observe changes in pathological tissue and synaptic morphology, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of orexin-A and acetylcholine. The expression levels of orexin receptor 1 (OXR1), melatonin receptor 1 (MT1A), melatonin receptor 2 (MT1B), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) were detected by immunohistochemistry and Western blot. Results In the present study, rats in the model group showed significant behavioral changes as well as a reduction in hippocampal dendritic branch length and synaptic number, along with increasing the content of orexin A and acetylcholine (P< 0.05), and altered expression levels of OX1R, MT1A, MT1B, ChAT, and AChE in the hippocampus and prefrontal cortex after modeling (P < 0.05). CCJJYT can improve depressive insomnia behavior and synaptic plasticity of rats (P < 0.05), which is similar to that of the positive drug group. It can also decrease the content of orexin A and acetylcholine, and reduce the expression levels of OXR1 and ChAT in hippocampus and prefrontal cortex (P < 0.05), and increase the expression levels of MT1A, MT1B, and AChE proteins (P < 0.05). Conclusion CCJJYT has good antidepressant and insomnia effects, probably through the regu-lation of orexin-A, melatonin, and acetylcholine content in hippocampus and prefrontal cortex of rats, improving synaptic plasticity and thus exerting antidepressant and insomnia effects.