BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E₂-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

OBJECTIVE To investigate the correlation between gene polymorphisms and adverse drug reaction （ADR） and demands of opioids， aiming to guide personalized opioid analgesic therapy. METHODS The existing evidence-based medical data were adopted to identify gene loci related to the efficacy and ADR of opioid analgesics and select highly relevant single nucleotide polymorphism （SNP） for a clinical case-control study. The study cohort was divided into two evaluation groups： ADR assessment and drug demand assessment. The ADR assessment group included 254 cancer pain patients and was subdivided into the trial subgroup （with ADR） and the control subgroup （without ADR） based on the presence or absence of ADR following opioid usage； the two subgroups included 126 and 128 patients， respectively. The drug demand assessment group included a total of 120 cancer pain patients， who were divided into trial subgroup （equivalent to a daily dose of oral morphine ≥100 mg） and control subgroup （equivalent to a daily dose of oral morphine ＜100 mg） based on the different daily doses of opioid analgesics， with 60 patients in each subgroup. Polymorphism detection of SNP loci in these patients was performed using fluorescence in situ hybridization. SPSS 21.0 software and SNPStats genetic models were employed to compare genetic testing results between subgroups and conduct correlation analyses， aiming to evaluate the association of the selected SNP loci with opioid ADR and drug demand inclinical real-world cases. RESULTS The strongly correlated SNP loci identified were CYP2D6*10（rs1065852，C＞T）， CYP3A5*3（rs776746，A＞G），ABCB1（rs1045642，C＞T）and OPRM1（rs1799971，A＞G）. Genetic testing results indicated that the allele frequency distributions of these SNP loci conformed to Hardy-Weinberg equilibrium. Correlation analysis revealed that in the ADR assessment group， compared with control subgroup， the proportion of patients in trial subgroup with the AA genotype of OPRM1 （rs1799971， A＞G） was significantly higher （P＜0.05）； in the drug demand assessment group， compared with control subgroup， the proportion of patients in trial subgroup with the CC+CT genotype of ABCB1 （rs1045642， C＞T） was significantly higher （P＜0.05）. CONCLUSIONS The AA genotype of OPRM1 （rs1799971， A＞G） is associated with the occurrence of ADR following oxycodone use. Patients with the CC+ CT genotype of ABCB1（ rs1045642， C＞T） require higher doses of opioid analgesics.

AIM:To investigate the effects of Xiaozhong-Zhitong mixture(XZZT)on M2 polarization and Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway in mouse microglia(BV2 cells).METHODS:The BV2 cells were divided into 5 groups:blank group,model group[lipo-polysaccharide(LPS)+hypoxia],TAK-242(resatorvid,a TLR4 inhibitor)group(LPS+hypoxia+TAK-242),XZZT group(LPS+hypoxia+XZZT),and TAK-242+XZZT group(LPS+hypoxia+TAK-242+XZZT).Flow cytometry was used to detect early apoptosis and cell cycle of BV2 cells,and immunofluorescence staining was employed to detect the positive expres-sion of M1-type marker inducible nitric oxide synthase(iNOS)and M2-type marker CD206.Western blot was utilized to detect the expression of TLR4/MyD88/NF-κB signaling pathway-related proteins,including TLR4,MyD88,NF-κB p65,phosphorylated p65(p-p65),phosphorylated transforming growth factor-β-activated kinase 1(p-TAK1),and phosphory-lated IκB kinase α/β(p-IKKα/β).RT-qPCR was used to detect the mRNA expression of interleukin-1β(IL-1β),IL-10,tumor necrosis factor-α(TNF-α),TLR4,MyD88,and NF-κB p65.RESULTS:Compared with model group,the rate of early apoptosis was significantly decreased in XZZT group(P<0.01),the percentage of cells arrested in the S phase was significantly increased(P<0.01),and the protein levels of TLR4,MyD88,NF-κB p65,p-IKKα/β,p-p65,and p-TAK1 were significantly decreased(P<0.05 or P<0.01).Additionally,IL-1β,TNF-α,TLR4,MyD88 and NF-κB p65 mRNA expression levels were significantly decreased(P<0.05 or P<0.01),while IL-10 mRNA expression was significantly in-creased(P<0.05).Compared with TAK-242 group,the average percentage of iNOS positive area was significantly de-creased,while CD206 was significantly increased in TAK-242+XZZT group(P<0.01).CONCLUSION:The XZZT has the effect of inducing M2 polarization of mouse microglia,and the mechanism may be linked to the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas. Flap survival is closely related to a variety of factors including cellular autophagy, oxidative stress, inflammatory response, mesenchymal stem cells (MSCs) function, and vascular regeneration. Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair. Excessive oxidative stress and inflammatory responses pose a threat to flaps, affecting their survival and successful transplantation. Endothelial cells are involved in vascular regeneration through proliferation, migration, and production of angiogenic factors, and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action. The multiple roles played by cellular autophagy, oxidative stress, inflammatory response, MSCs function, and vascular regeneration in influencing postoperative flap survival are hereby elaborated. The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival, improve the success rate of flap surgery, reduce complications, and bring more hope for the recovery and quality of life of patients.

The prevalence of osteoporosis， osteoarthritis， gouty arthritis， rheumatoid arthritis， and intervertebral disc degeneration is increasing year by year with the growing number of elderly people， and the common clinical manifestations of these diseases include severe pain in different areas， which seriously affects the daily life of the patients. Therefore， how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family， pyrin domain-containing protein 3 （NLRP3） inflammasomes， as pattern recognition receptors， are involved in the inflammation， chondrocyte proliferation， osteoblast and osteoclast differentiation， intervertebral disc cell inflammation and scorching， extracellular matrix degradation and apoptosis， mitochondrial dysfunction， endoplasmic reticulum stress， and reactive oxygen species damage， demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain， playing a role in preventing and treating these diseases. Therefore， this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components， extracts， and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Autoimmune epilepsy (AE) is a type of epilepsy mediated by autoantibodies and immune cells. The main pathogenesis of AE is that autoimmune antibodies related to AE interact with surface of nervous cell membrane antigens or intracellular antigens, which leads to the disorder of excitatory and inhibitory nervous system and causes epileptic seizures. Glutamate receptor subunit 3 peptide B antibodies (GluR3B Ab's) are one type of anti-neuron autoantibodies related to AE, and they can combine with GluR3B subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), which causes an increase of intracellular calcium. Intracellular calcium overload further leads to dysregulation of energy metabolism in neurons or oligodendrocyte progenitor cells (OPCs). The damage of neurons or OPCs eventually trigger seizure. Here, we mainly discuss the mechanisms of GluR3B Ab's involving in the development of autoimmune epilepsy.

Objective:To observe the effects of low intensity pulsed ultrasound(LIPUS) on the osteogenic differentiation of rat bone marrow mesenchymal stem cells(BMSCs) on titanium surface.Methods:BMSCs from Wistar rat bone marrow were respectively cultured on the flat titanium surface and the large grain blast acid etched(SLA) titanium surface,and induced by mineralization medium.Then,the cells were interfered by LIPUS and a control condition.Alkaline phosphatase(ALP) were quantitative determinated after 3 and 7 d mineralization induction respectively,ALP staining were observed after 14 d induction.Alizarin red staining were observed after 21 d mineralization induction.Osteogenic related protein and gene expressions were detected after mineralization induction.Results:ALP in culture medium of LIPUS group was higher than that of the control group after 3 d and 7 d mineralization induction(P＜0.05).LIPUS group showed stronger ALP staining and alizarin staining,and more mineralized nodules than control group.The expression of osteogenic related proteins,including Runx2,BMP2,OPN in LIPUS group increased.Osteogenic related genes expression,including ALP,Runx2,BMP2,OPN,OCN and Col-1 of the LIPUS group increased.Conclusion:The osteogenic differentiation of BMSCs on the fiat titanium surface or SLA titanium surface can be promoted by LIPUS.

Objective To study the value of magnetic resonance vessel wall imaging in assessing the atherosclerotic plaque burden of rabbit model.Methods We built up abdominal atherosclerotic animal model in 30 New Zealand rabbits by high lipid diet combined with abdominal artery denudation.The animals were divided into 3 groups randomly,which were the 1-week group,1-month group and 2-months group.The MRI and histology examination were carried out at relative time points.The correlations of area or thickness of vessel wall by MRI with histology examination were analyzed.Results Among the 30 rabbits,3 died due to anesthesia or surgery,one rabbit model failed because of the thin vessel,and another 3 died of diarrhea or inflammation during the high lipid diet feeding.Eventually,totally 23 rabbits fulfilled the examinations (7 in 1-week group,7 in 1-month group and 9 in 2-months group).The vessel wall area of histology examination grew larger along with the post-surgery duration,from 1.7663 mm2of 1-week group to 2.4371 mm2 of the 1-month group till 3.5978 mm2 of 2-months group,with statistic significant difference among 3 groups (F=5.052,P=0.017).There were strong correlations of area or thickness vessel wall resulted from MRI with histology examination(r=0.688,0.642;P=0.001,0.002).Conclusions High resolution MR vessel wall imaging technique may evaluate and follow up the plaque burden in the early stage of atherosclerosis.