ObjectiveTo observe the effects of Tongmai Kaiqiao pills on AMP-activated protein kinase （AMPK）/peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α） signaling pathway and mitochondrial biogenesis in hippocampal tissue of rats with vascular cognitive impairment （VCI） and to investigate the potential mechanism of Tongmai Kaiqiao pills in improving cognitive impairment in rats with VCI. MethodsTwelve of 72 male SD rats were selected as the sham operation group， and the remaining rats were modelled using the modified 2VO method. The rats that were successfully modelled were divided into the model group， the high-dose group of Tongmai Kaiqiao pills （27.6 g·kg^-1）， the low-dose group of Tongmai Kaiqiao pills （13.8 g·kg^-1）， the combination group （27.6 g·kg^-1 Tongmai Kaiqiao pills + 25 mg·kg^-1 dorsomorphin）， and the donepezil hydrochloride group （0.45 g·kg^-1） according to the random number table method. After four weeks of continuous intraperitoneal injection of the corresponding drugs， the Morris water maze test was used to test the learning and memory ability of rats. Hematoxylin-eosin （HE） staining and Nissl staining were used to detect pathological changes in the hippocampus of the rats. The content of mitochondrial adenosine triphosphate （ATP） in the brain hippocampus was detected by colorimetry， and reactive oxygen species （ROS） level was detected in rat mitochondria by MitoSOX Red assay. Mitochondrial DNA copy number was detected by real-time fluorescent quantitative PCR （Real-time PCR）. Pathological changes in mitochondria were observed by transmission electron microscopy （TEM）， and AMPK， PGC-1α， phosphorylated AMP-activated protein kinase （p-AMPK）， nuclear respiratory factor 1 （Nrf1）， and mitochondrial transcription factor A （TFAM） protein expression in the hippocampus of the rats were detected by Western blot. ResultsCompared with those in the sham operation group， rats in the model group had a reduced number of platform crossings （P<0.01）， significantly prolonged evasion latency （P<0.01）， disorganized neuronal arrangement in the hippocampal region， widened gaps， and blurred nucleus membrane and nucleolus boundaries. The emergence of necrotic cells was visible. The color of the nissl bodies was light， and the number was reduced with severe loss. Mitochondria were atrophied， and cristae were lost. Severe damage was observed. The content of ROS was increased， and the level of ATP was decreased. mtDNA copy number decreased significantly （P<0.01）， and the protein expression of p-AMPK， PGC-1α， Nrf1， and TFAM decreased （P<0.05， P<0.01）. Compared with those in the model group， rats in the high-dose group of Tongmai Kaiqiao pills and donepezil hydrochloride group showed a shorter time to find the platform （P<0.01）， increased number of platform crossings （P<0.01）， restored mitochondrial morphology and structure of the hippocampal neurons， alleviated neuronal death， increased number of nissl bodies， weaken degree of injury， lower content of ROS， and significantly increased levels of ATP and number of copies of mtDNA （P<0.05， P<0.01）. In addition， there was increased protein expression of p-AMPK， PGC-1α， Nrf1， and TFAM （P<0.05， P<0.01）. Compared with the model group， the evasion latency was shortened in the low-dose group of Tongmai Kaiqiao pills （P<0.01）， and the number of platform crossings was increased， but the difference was not statistically significant. The mitochondria were swollen and deformed， and the cristae became shorter and partially disappeared. The degree of damage did not improve significantly， and the number of nissl bodies was increased but not statistically significant. The ROS content decreased （P<0.01）， but there was no significant difference in ATP level and mtDNA copy number. The protein expression of PGC-1α was increased （P<0.05）， but there was no significant difference in the protein expression of p-AMPK， Nrf1， and TFAM， and the results were not statistically significant. Compared with the donepezil hydrochloride group， there was no significant change in the results of each assay in the high-dose group of Tongmai Kaiqiao pills， and the difference was not statistically significant. Compared with the high-dose group of Tongmai Kaiqiao pills， rats in the combination group had a significantly lower number of platform crossings （P<0.01）， a significantly longer evasion latency （P<0.01）， a reduced number of neuronal cells， disorganized tissue structure， swollen and blurred cell outlines， a significant reduction in the number of nissl bodies. Moreover， there was an increase in the content of ROS， a decrease in the level of ATP and the number of mtDNA copies （P<0.01）， and a decrease in the expression of p-AMPK， PGC-1α， Nrf1， and TFAM （P<0.05）. ConclusionTongmai Kaiqiao pills is able to improve cognitive function in rats by activating the AMPK/PGC-1α signaling pathway， promoting mitochondrial biogenesis， and attenuating pathological damage to neurons in the hippocampal region， thereby demonstrating its therapeutic potential.

Objective To explore the clinical value of serum stromal cell-derived factor-1(SDF-1)and macro-phage inflammatory protein-1α(MIP-1α)in predicting biliary tract infection after endoscopic retrograde cholangiopancreatography(ERCP)stone removal in patients with common bile duct stones.Methods From January 2022 to January 2024,100 patients with common bile duct stones who underwent ERCP stone removal surgery in Pingdingshan First People's Hospital were collected.They were grouped into an infection group(12 cases)and a non-infection group(88 cases)based on whether biliary tract infection occurred after surgery.The general information of patients in the two groups was compared.ELISA method was used to measure the levels of serum SDF-1 and MIP-1α.Spearman method was applied to analyze the correlation between the severity of infec-tion and serum level of SDF-1 and MIP-1α.ROC curve was applied to analyze the value of serum SDF-1 and MIP-1α to predict biliary tract infection after ERCP stone removal in patients with common bile duct stones.Results A total of 36 strains of pathogenic bacteria were detected in the biliary drainage fluid samples of the infection group,among which Gram-negative bacteria accounted for 55.56%and Gram-positive bacteria accounted for 44.44%.The infection group showed significantly higher serum levels of SDF-1 and MIP-1α(P＜0.05).As the infection wors-ened,SDF-1 and MIP-1α levels progressively increased(P＜0.05).The severity of biliary tract infection was sig-nificantly positively correlated with both serum SDF-1 and MIP-1α levels(P＜0.05).For predicting biliary tract in-fection,SDF-1 and MIP-1α exhibited AUC values of 0.761 and 0.825,sensitivities of 63.33%and 66.67%,and specificities of 83.33%and 83.33%,respectively.When combined,the predictive AUC reached 0.977,with a sensitivity of 83.33%and a specificity of 98.33%.Conclusions Serum level of SDF-1 and MIP-1α are significant-ly elevated in patients with common bile duct stones and biliary tract infections after ERCP stone removal surgery,showing a positive correlation with the severity of the infection.The combination of these two biomarkers demon-strates excellent predictive efficacy for postoperative infection.

Post-stroke cognitive impairment(PSCI) is one of the common complications in stroke patients, mainly manifested as impairments in memory, attention, and orientation. Adenosine monophosphate-activated protein kinase(AMPK), as a crucial intracellular energy sensor, has attracted extensive research attention in the field of PSCI in recent years. This paper provides a comprehensive review of the research progress on AMPK-related signaling pathways and their roles in PSCI, with a focus on exploring action mechanisms of AMPK in processes such as oxidative stress, neuroinflammation, autophagy, and apoptosis. Additionally, it summarizes the prospects and challenges of AMPK as a potential target for improving PSCI, aiming to offer new theoretical foundations for the clinical prevention and treatment of PSCI.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.

BACKGROUND:Our previous studies found that adding barium sulfate could improve the mechanical and radiopaque properties of calcium phosphate cement.However,with the degradation of calcium phosphate,the remaining radiopaque agent is difficult to degrade,and the space-occupying and osteoclast effects at the implantation site affect the bone repair process.Therefore,it is necessary to develop a new biodegradable radiopaque material. OBJECTIVE:To discuss the radiopaque ability of bioactive degradable material strontium polyphosphate(SrPP)and its impact on the physicochemical properties and osteogenic effect of calcium phosphate cement. METHODS:(1)Calcium phosphate cement(CPC),starch modified calcium phosphate cement(CPS)and starch modified calcium phosphate cement(20%SrPP-CPN)containing SrPP(20%mass fraction of bone cement powder)were prepared respectively,and the physicochemical properties of the three groups of bone cements were characterized.(2)The three groups of bone cement extracts were co-cultured with rat bone marrow mesenchymal stem cells,respectively,to detect cell proliferation,energy metabolism,and osteogenic differentiation.(3)Bone defects with a diameter of 5 mm were made on each side of the top of the skull of 24 SD rats,and they were randomly divided into control group(without any intervention),CPC group,CPS group,and 20%SrPP-CPN group for intervention,with 6 rats in each group.Relevant tests were performed after 4 and 12 weeks of intervention. RESULTS AND CONCLUSION:(1)Compared with the other two groups of bone cement,20%SrPP-CPN had enhanced radiopaque ability,increased compressive strength and degradation rate,and prolonged curing time,and 20%SrPP-CPN could release Sr2+ stably during degradation.(2)CCK-8 assay showed that 20%SrPP-CPN did not affect the proliferation of bone marrow mesenchymal stem cells.Cell starvation test(serum-free culture)showed that 20%SrPP-CPN could promote the proliferation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.Compared with the other two groups of bone cements,20%SrPP-CPN increased adenosine triphosphate concentration in bone marrow mesenchymal stem cells.Alkaline phosphatase and alizarin red staining showed that 20%SrPP-CPN could promote osteogenic differentiation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.(3)In the rat skull defect experiment,Micro-CT scanning and histological observation(hematoxylin-eosin and Masson stainings)showed that bone cement in 20%SrPP-CPN group was significantly degraded compared with that in CPC and CPS groups,and a large number of new bone tissues were dispersed in degraded bone cement.Immunohistochemical staining showed that Runx2 protein expression was increased in 20%SrPP-CPN group compared with CPC group and CPS group(P＜0.01).(4)These results show that 20%SrPP-CPN has good radiopaque ability and osteogenic properties.

Keloid is a common skin disease, and the mechanism of its occurrence is not fully understood. There is evidence to show that multiple factors such as genetics, race, age, gender, hormones, infection, immunity, and oxidative stress, etc. may be related to the occurrence of keloids. Metabolic remodeling and protein acylation modification, as two important biological processes, play important roles in various skin related diseases. Based on this, this article reviews the roles of metabolic remodeling and protein acylation modification in keloids and the interrelationship between the two biological processes, and explores the application prospects of targeting the two biological processes in the prevention and treatment of keloids.

As a key regulator of neuronal growth,development and synaptic plasticity,BDNF/TrkB signaling path-way is widely involved in the occurrence and development of central nervous system diseases,such as ischemic stroke,Al-zheimer's disease,Parkinson's disease and spinal cord injury.Studies have shown that acupuncture can regulate the activi-ty of BDNF/TrkB signaling pathway,and has significant therapeutic potential for these diseases.Its mechanism of action is related to participating in synaptic remodeling,inhibiting neuronal apoptosis,and promoting neurogenesis or synaptic re-generation.This article reviews the role of BDNF/TrkB signaling pathway in central nervous system diseases and the regula-tion mechanism of acupuncture on this pathway,in order to provide new ideas for clinical treatment.Future studies should further explore the precise regulatory mechanism of acupuncture on BDNF/TrkB signaling pathway in order to develop more efficient and safe treatment strategies.

Post-stroke cognitive impairment(PSCI)is a common complication after stroke,which significantly affects quality of life.However,the pathogenesis has not been fully explained.Increasing evidence has shown that the mechanism of programmed cell death(PCD)is related to PSCI,including apoptosis,necroptosis,pyroptosis,PANoptosis,parthanatos,and ferroptosis.Therefore,it is crucial to clearly understand the various mechanisms of PCD and their relationship with PSCI,and to elucidate the role of PCD in PSCI pathogenesis.The article reviews six PCD pathways related to PSCI,summarizes their mechanisms of action in PSCI,and elucidates the possible crosstalk among pathways to provide a basis for clinical targeting of regulatory factors in the PCD pathway for PSCI treatment.