Age-related macular degeneration(ARMD)is a progressive visual impairment fundus disease that frequently occurs in individuals aged >55 years. The main risk factors are aging, long-term smoking, genetics, and racial differences. Pathogenesis includes abnormal function of the retinal pigment epithelium, damaged blood-retinal barrier, and abnormal immune function. Currently, intravitreal injection(IVI)of anti-vascular endothelial growth factor(VEGF)drugs is the preferred treatment option for ARMD in clinical practice. However, it also faces challenges such as repeated treatments, high medical costs, and poor patient compliance. The predicament in the treatment of ARMD has given rise to several new treatment options. This article aims to review the treatment methods and progress of dry ARMD and wet ARMD, providing new ideas for addressing the limitations of the current clinical anti-VEGF treatment.

OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.

Pancreatic cancer is a highly malignant solid tumor of the digestive system with extremely poor treatment prognosis. Although its incidence rate is low， its mortality rate is extremely high. In recent years， the number of diagnosed cases worldwide has continued to rise， making pancreatic cancer the sixth leading cause of cancer-related deaths globally. Currently， clinical treatment primarily relies on operation and chemotherapy to suppress tumors. However， these approaches face challenges such as suboptimal efficacy， high postoperative recurrence rates， and severe adverse reactions. Therefore， identifying safe and effective treatment modalities remains a pressing challenge for the medical community. In recent years， research on traditional Chinese medicine （TCM） interventions for pancreatic cancer has increased significantly. Multiple studies have shown that single-herb TCM， TCM formulas， and their derived single compounds can regulate the levels of tumor cell signaling pathways through multiple action targets. They inhibit the development and progression of pancreatic cancer by inhibiting cancer cell proliferation， promoting cell apoptosis， inhibiting tumor angiogenesis， reducing cancer cell invasion and migration capabilities， regulating the cell cycle， and modulating the tumor microenvironment. Additionally， TCM has the advantages of significantly enhancing the anticancer efficacy of chemotherapy drugs and causing fewer adverse reactions. However， the specific action mechanisms by which TCM intervenes in pancreatic cancer remain unclear. Further extensive research is still needed to validate the role of regulating classical signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， nuclear transcription factor-κB （NF-κB）， notch， and hedgehog in the treatment of pancreatic cancer. Therefore， this paper reviewed Chinese and international studies on TCM intervention in pancreatic cancer through relevant signaling pathways in recent years， summarized the potential action mechanisms of TCM in the treatment of pancreatic cancer， and provided references for related research in the future.

ObjectiveTo investigate the status of overlapping hepatitis B virus （HBV） infection in patients with chronic hepatitis C virus （HCV） infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1， 2010 to December 31， 2020 and had complete data of HBV serological markers were enrolled， and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth， and serological characteristics were analyzed， and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%， and the patients with previous HBV infection accounted for 48.10%； the patients with protective immunity against HBV accounted for 14.67%， while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age： in the 0 — 17 years group， the patients with protective immunity against HBV accounted for 61.41% （304 patients）； the 18 — 44 years group was mainly composed of patients with previous HBV infection （698 patients， 37.31%）， the 45 — 59 years group was predominantly composed of patients with previous HBV infection （1 945 patients， 50.38%）， and the ≥60 years group was also predominantly composed of patients with previous HBV infection （1 486 patients， 61.66%）. The patients were divided into groups based on the year of birth： in the pre-1992 group， the patients with previous HBV infection accounted for 51.63% （4 112 patients）； in the 1992 — 2005 group， the patients with protective immunity against HBV accounted for 54.72% （168 patients）； in the post-2005 group， the patients with protective immunity against HBV accounted for 64.38% （235 patients）. In this study， 6 301 patients underwent HCV genotype testing： the patients with genotype 1b accounted for the highest proportion of 51.71% （3 258 patients）， followed by those with genotype 2a （1 769 patients， 28.07%）， genotype 3b （63 patients， 1.00%）， genotype 3a （10 patients， 0.16%）， genotype 4 （21 patients， 0.33%）， and genotype 6a （5 patients， 0.08%）. ConclusionWith the implementation of hepatitis B planned vaccination program in China， there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection， but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

The welfare and ethics of laboratory animals are the ethical principles and behavioral norms that need to be followed in conducting animal-based scientific research, breeding and managing laboratory animals, and supervising and regulating such activities. The level of protection of laboratory animal welfare and ethics is closely related to the development of science and technology, which has become a widely recognized international consensus. At present, Guangdong Province is accelerating the construction of a high-level science and technology innovation province and the Guangdong-Hong Kong-Macao Greater Bay Area International Science and Technology Innovation Center. Guangdong Province should rely on its advanced governance capacity in the field of laboratory animal science and technology ethics to promote the high-quality development of its laboratory animal science and technology sector. Based on the management laws, regulations, and institutional mechanisms of laboratory animals in China, this paper explores the optimization of the laboratory animal science and technology ethics governance system, which includes the institutional guarantees, responsibility systems, ethical review and supervision mechanisms, and education and outreach. Through methods such as literature research, questionnaire surveys, and interview investigations, an empirical study of the laboratory animal science and technology ethics governance system in Guangdong Province has been conducted. Analysis of literature and research results shows that Guangdong Province has basically established a laboratory animal management system, collaboration mechanism, supervision mechanism, and education and training system that meet the current requirements of the laboratory animal science and technology ethics governance system in China. However, there are still problems such as an incomplete laboratory animal science and technology ethics supervision mechanism, an underdeveloped operation mechanism of review institutions, insufficient attention paid by laboratory animal units to the ethical review of animal experiments, inconsistent ethical review standards, and a lack of professional ethical education and training for ethics review personnel. Therefore, optimization measures such as improving the laboratory animal science and technology ethics review system, strengthening supervision and inspection, further strengthening the accountability of responsible entities, formulating review norms, and enhancing hierarchical and classified education and training are proposed, to provide a theoretical basis for promoting the normalized and long-term governance of laboratory animal science and technology ethics in Guangdong Province.