ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P＜0.05),the expression of IBA1 in CX decreased(P＜0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P＜0.01).The results of ELISA showed that the levels ofTNF-α(P＜0.01),IL-6(P＜0.01),IL-1β(P＜0.05)and IL-17A(P＜0.01)significantly decreased,while the ex-pression of BDNF increased(P＜0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P＜0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.

Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature， and ginger is used to restrict the bitter cold of Coptidis Rhizoma， which can be traced back to Bojifang， and it is suitable for stagnation of damp-heat in middle-jiao， cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids， phenylpropanoids and flavonoids of Coptidis Rhizoma， and also introduces gingerol components such as 6-gingerol in ginger， which has pharmacological activities such as anti-inflammatory， antibacterial， anti-tumor， and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian， but the specific process parameters and quality standards are incomplete， which limits the production and clinical application of this processed product. By summarizing the processing history， process research， quality evaluation， pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years， there are differences in the processing methods and standards in various provinces and cities， which are mainly reflected in the preparation method， dosage， processing process and quantitative standards of ginger juice. In addition， there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger， as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards， and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

As an important part of Chinese traditional culture， the processing technology of traditional Chinese medicine（TCM） carries the wisdom of TCM for thousands of years， and its process is complex and rigorous. With the popularization of modern production technology， traditional processing techiques are facing the dual pressures from technological innovation and production standardization under the perspective of intangible cultural heritage. The modernization of TCM processing technology is an inevitable trend for industrial upgrading， but it cannot be separated from the foundation of traditional skills and ignore the core concepts and cultural values it embodies. Therefore， by analyzing the core characteristics of TCM processing technology and its differences with modern production， this paper discusses the establishment of a synergistic innovation mechanism between traditional techniques and modern technologies， the promotion of joint research and development between scientific research institutes and the industry， the strengthening of standardization of processing techniques， and the enhancement of social education and industry training to improve the recognition and inheritance of processing techniques in order to achieve the goal of innovation and protection of TCM processing technologies in the context of modernization， and to promote the high-quality development of the TCM processing industry.

Objective:It is of great significance to analyze the expression characteristics of immune-related genes in pancreatic cancer and their relationship with prognosis,construct and verify a reliable prognostic model,and explore prognostic methods of pancreatic cancer from the perspective of immune microenvironment.Methods:GSEA enrich-ment analysis of differentially expressed genes in pancreatic cancer was performed to identify key immune-related pathways and genes.The genes involved in the immune pathway were screened through the STRING database and combined with univariate Cox regression and LASSO regression analysis.Three key genes,RIPK2,IRAK2 and CXCL11,were finally identified to construct the prognostic model.The accuracy of the model was evaluated using ROC curves and calibration curves,and verified in an independent verification set(GSE57495).At the same time,the expression pat-terns of key genes in the immune microenvironment were analyzed by single-cell RNA sequencing,and the expression levels of these genes were verified in pancreatic cancer cell lines by RT-qPCR.Results:The expressions of RIPK2,IRAK2 and CXCL11 in pancreatic cancer cell lines were higher than those in normal pancreatic cancer cells(P<0.05).The model based on these three genes divided the patients into a high-risk group(n=87)and a low-risk group(n=89),and the difference in survival time between the high-risk group and the low-risk group was statistically significant(P<0.001).Risk score was correlated with G stage,N stage and tumor residue(P<0.01).Single-cell analysis showed that the ex-pression of these genes was highest in tumor-associated macrophages(mean>0.5)and correlated with regulatory T cells and macrophage infiltration(P<0.05).Multivariate analysis showed that risk score was correlated with overall sur-vival after adjusting for clinical factors(P=0.0014).Conclusion:Based on three key immune-related genes(RIPK2,IRAK2 and CXCL11),we successfully constructed a model to accurately predict the prognosis of pancreatic cancer pa-tients,revealing the important role of these genes in the tumor immune microenvironment,and providing new insights and theoretical basis for pancreatic cancer prognosis assessment and immunotherapy research.

Objective:It is of great significance to analyze the expression characteristics of immune-related genes in pancreatic cancer and their relationship with prognosis,construct and verify a reliable prognostic model,and explore prognostic methods of pancreatic cancer from the perspective of immune microenvironment.Methods:GSEA enrich-ment analysis of differentially expressed genes in pancreatic cancer was performed to identify key immune-related pathways and genes.The genes involved in the immune pathway were screened through the STRING database and combined with univariate Cox regression and LASSO regression analysis.Three key genes,RIPK2,IRAK2 and CXCL11,were finally identified to construct the prognostic model.The accuracy of the model was evaluated using ROC curves and calibration curves,and verified in an independent verification set(GSE57495).At the same time,the expression pat-terns of key genes in the immune microenvironment were analyzed by single-cell RNA sequencing,and the expression levels of these genes were verified in pancreatic cancer cell lines by RT-qPCR.Results:The expressions of RIPK2,IRAK2 and CXCL11 in pancreatic cancer cell lines were higher than those in normal pancreatic cancer cells(P<0.05).The model based on these three genes divided the patients into a high-risk group(n=87)and a low-risk group(n=89),and the difference in survival time between the high-risk group and the low-risk group was statistically significant(P<0.001).Risk score was correlated with G stage,N stage and tumor residue(P<0.01).Single-cell analysis showed that the ex-pression of these genes was highest in tumor-associated macrophages(mean>0.5)and correlated with regulatory T cells and macrophage infiltration(P<0.05).Multivariate analysis showed that risk score was correlated with overall sur-vival after adjusting for clinical factors(P=0.0014).Conclusion:Based on three key immune-related genes(RIPK2,IRAK2 and CXCL11),we successfully constructed a model to accurately predict the prognosis of pancreatic cancer pa-tients,revealing the important role of these genes in the tumor immune microenvironment,and providing new insights and theoretical basis for pancreatic cancer prognosis assessment and immunotherapy research.

Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P＜0.05),the expression of IBA1 in CX decreased(P＜0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P＜0.01).The results of ELISA showed that the levels ofTNF-α(P＜0.01),IL-6(P＜0.01),IL-1β(P＜0.05)and IL-17A(P＜0.01)significantly decreased,while the ex-pression of BDNF increased(P＜0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P＜0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

Yuhuanglian is one of the representative processed products to change the medicinal properties of Coptidis Rhizoma， which was first published in Hanshi Yitong. Its processing method is to mix Evodiae Fructus juice with Coptidis Rhizoma with stir-frying for drying， that is， Coptidis Rhizoma processed with Evodiae Fructus juice can reduce the bitterness and cold properties on the basis of retaining the effect of purging fire and detoxification， so that Yuhuanglian is cold but not stagnant， which can clear dampness-heat in Qifen， and is effective in treating the liver-qi invading stomach， vomiting and swallowing acid. As a representative variety of processing with medicine juice， Yuhuanglian is included in the 2020 edition of Chinese Pharmacopoeia and local processing standards， and its processing technology research and optimization has been attracting much attention. Modern studies have shown that Yuhuanglian not only contains berberine， jatrorrhizine， palmatine and other components， but also contains evodiamine， rutaecarpine， limonin and other components from Evodiae Fructus， which have anti-inflammatory， antibacterial， anti-tumor and other pharmacological activities. This paper collated and summarized the related research reports of Yuhuanglian in the past 20 years from the perspectives of processing history， efficacy and medicinal properties， quality evaluation and clinical application， and found that the processing methods and standards of Yuhuanglian were quite different in different provinces and cities， mainly involving the preparation and dosage of Evodiae Fructus juice and the criteria for the processing end point. In addition， the changes in the major components of Yuhuanglian before and after processing varied greatly among different studies， presumably related to the different processes and quality standards， this paper summarized the processing history， technology， pharmacodynamics， quality evaluation and clinical application of Yuhuanglian， in order to provide reference for improving its quality evaluation system.