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.

OBJECTIVE To optimize the forming process of Yindan huoxue tongyu granules， and evaluate the quality of the granules. METHODS Taking forming rate， angle of repose， moisture， moisture absorption rate and dissolution rate as indexes， single factor experiment combined with Plackett-Burman design was adopted to screen key process parameters； analytic hierarchy process combined with entropy weight method and Box-Behnken response surface method were used to optimize the molding process of Yindan huoxue tongyu granules， and the forming process was verified. The relative homogeneity index， bulk density， vibration density， Hausner ratio， angle of repose， moisture and hygroscopicity were used as secondary physical indexes to establish the physical fingerprints of 10 batches of Yindan huoxue tongyu granules to evaluate particle quality consistency. RESULTS The optimal molding process of Yindan huoxue tongyu granules was as follows： mannitol as the fixed excipient， the drug-assisted ratio was 1∶1（m/m） and the drying time was 1 h； 90% ethanol was used as wetting agent and the amount of it was 32%， the drying temperature was 70 ℃. The results of validation tests showed that the average comprehensive score was 97.45， which was close to the predicted value of 97.18. The similarities between the physical fingerprints of 10 batches of Yindan huoxue tongyu granules prepared by the optimal molding process and the reference physical fingerprint were all higher than 0.99. CONCLUSIONS The molding process is stable and feasible， and the quality of Yindan huoxue tongyu granules produced is stable and controllable.

OBJECTIVE To evaluate the quality of Yindan huoxue tongyu granules. METHODS Taking high performance liquid chromatography with ultraviolet and evaporative light scattering detection as method， the fingerprint of 15 batches of Yindan huoxue tongyu granules was established， and similarity evaluation was performed by Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to determine common peaks. The common peaks were identified by comparing with reference substance chromatograms and single decoction piece chromatograms. Network pharmacology was used to screen out core targets and pathways of identified components， construct a “component-target-pathway” network diagram， and predict the pharmacodynamic components of Yindan huoxue tongyu granules， and the content determination of these components was carried out by the same method. RESULTS HPLC fingerprints of 15 batches of Yindan huoxue tongyu granules were characterized with 40 common peaks， and 17 components including salvianolic acid B， astragaloside Ⅳ， notoginsenoside R1， and ginkgolide A were identified. Network pharmacology predicted that 17 components mainly acted on 97 core targets and 137 pathways to exert their pharmacological effect. Average contents of 13 bioactive components in 15 batches of samples were 0.126 8， 0.232 0， 0.073 8， 0.353 2， 3.620 2， 0.191 0， 0.333 3， 0.317 4， 0.785 0， 0.538 2， 0.460 0， 2.475 1 and 0.347 7 mg/g， including calycosin-7-O-β-D-glucoside， rosmarinic acid， formononetin， lithospermic acid， salvianolic acid B， ononin， ginsenoside Rb1， ginsenoside Rd， ginkgolide C， ginkgolide A， ginkgolide B， notoginsenoside R1， and astragaloside Ⅳ. CONCLUSIONS The established fingerprint of Yindan huoxue tongyu granules can reflect the overall characteristics of the preparation. The content determination method for its pharmacodynamic components， developed in combination with network pharmacology， is accurate， reliable， and exhibits good repeatability， making it suitable for evaluating the quality of Yindan huoxue tongyu granules.

OBJECTIVE To provide reference for the safe use of bevacizumab in cancer patients. METHODS The diagnosis and treatment of a 65-year-old female lung adenocarcinoma patient with diabetic ketoacidosis （DKA） induced by bevacizumab was retrospectively analyzed， and the possible mechanisms and causes were analyzed based on literature review. RESULTS & CONCLUSIONS The diagnosis and treatment process of patients were analyzed， and DKA caused by other drugs and disease factors were excluded. DKA was considered to be caused by the use of bevacizumab according to Naranjo’s ADR evaluation scale； the acidosis of the patient improved rapidly after one hemodialysis treatment. DKA caused by bevacizumab is rare in clinic， clinicians should be aware that bevacizumab may affect pancreatic function and induce DKA， and early detection and treatment should be achieved to improve the prognosis.

BACKGROUND:In recent years,it has been found that some traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of the skin flap,promote vascular regeneration of the skin flap and prevent skin flap necrosis by activating autophagy. OBJECTIVE:To review the research progress of traditional Chinese medicine monomer regulating autophagy in preventing flap necrosis. METHODS:The Chinese and English key words were"traditional Chinese medicine(TCM),autophagy,skin flaps".The first author searched the relevant articles published in CNKI and PubMed databases from January 2010 to October 2022.A total of 196 articles were retrieved in the preliminary screening and then screened according to the inclusion and exclusion criteria.The quality assessment was conducted by reading the literature titles and abstracts.Finally,55 articles were summarized. RESULTS AND CONCLUSION:(1)The regulation of autophagy is mediated by AMPK/mTOR,PI3K/AKT and other signaling pathways.Activation of autophagy can alleviate the oxidative stress and apoptosis of the flap,promote the regeneration of blood vessels in the flap,and prevent flap necrosis.(2)Terpenoids(Betulinic acid,Andrographolide,Notoginseng Triterpenes,Catalpa),phenolic compounds(Resveratrol,Curcumin,Gastrodin),phenolic acids(Salvianolic acid B)and steroid compounds(Pseudoginsenoside F11)in traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of skin flap by regulating related signaling pathways to activate autophagy,promote skin flap angiogenesis and promote skin flap survival.(3)Studying the research progress of traditional Chinese medicine monomer to prevent flap necrosis by regulating autophagy can provide a reference and theoretical basis for traditional Chinese medicine to prevent flap necrosis and promote flap healing in the clinic.

BACKGROUND:Endoscopic treatment of lumbar disc herniation has obvious advantages over traditional open surgery.Endoscopic surgery involves the implantation of a working cannula,which requires only partial bone removal,and there are no studies on the effects of two types of intraoperative foraminoplasty and laminoplasty on the mechanical properties of the local structure of the lumbar spine. OBJECTIVE:To compare the effect of foraminoplasty and laminoplasty on the biomechanical properties of disc and isthmus of the responsible segment. METHODS:The lumbosacral CT images of a healthy male volunteer were taken,and a finite element model M0 of the L3 to sacral vertebrae was established,on which the primary and secondary foraminoplasty models M1 and M2 of the L5/S1 and the laminoplasty model M3 were built.The same load was applied to compare the intervertebral motion range,disc Von Mises stress and equivalent stress characteristics of L5 vertebral isthmus with each model. RESULTS AND CONCLUSION:(1)Compared with M0,M1 and M2 motion range in L5/S1 segment did not change significantly in all directions;M2 overall motion range increased by 8.60%in flexion;M3 increased by 8.23%and 8.26%in L5/S1 right bending and right torsion,and 5.39%and 5.67%in overall motion range in flexion and right bending,with no significant changes in motion range in the rest of working conditions.(2)Compared with M0,M1 showed no significant change in the extremes of Von Mises stress at L5/S1 disc;M2 increased 11.06%,12.50%,18.32%,and 15.48%in flexion,extension,left torsion,and right torsion;M3 increased 12.22%,19.54%,10.05%,and 9.97%in flexion,extension,left torsion,and right torsion,and the rest working conditions and L4/5 disc maximum Von Mises stress did not change significantly.(3)Compared to M0,the maximum Von Mises stress in the left isthmus of L5 of M1 increased by 12.43%in left bending,18.38%,13.29%,13.62%,and 40.00%in the right isthmus in extension,right bending,left torsion,and right torsion.The maximum Von Mises stress in the left isthmus of L5 of M2 increased by 38.87%,42.63%,16.95%,and 19.35%,and that in the right isthmus increased by 12.58%,33.70%,12.92%,and 17.42%in flexion,extension,left bending,and left torsion.The maximum Von Mises stress in the left isthmus of L5 of M3 increased 67.07%,78.14%,32.33%,62.94%,and 89.99%in flexion,extension,left and right bending,and right torsion.(4)The results suggest that foraminoplasty and laminoplasty have a small effect on spinal motion range;there is a mild increase in the extreme values of disc Von Mises stress in the segments operated by interbody laminoplasty and secondary foraminoplasty;there is no significant change in the extreme values of disc Von Mises stress in adjacent segments,and there is a significant increase in the Von Mises stress in the ipsilateral isthmus operated by the interbody laminoplasty model.

BACKGROUND:Mesenchymal stem cells have great potential in the treatment of ischemia-reperfusion injury of skin flaps.However,their defects and the decline of their role in the treatment of ischemia-reperfusion injury of skin flaps restrict their wide application. OBJECTIVE:To review the strategies for improving the treatment of ischemia-reperfusion injury of skin flaps with mesenchymal stem cells,and provide a reference for its further theoretical research and clinical application. METHODS:Relevant documents included in CNKI,WanFang and PubMed were searched.The Chinese and English search terms were"mesenchymal stem cell,ischemia-reperfusion adjustment of skin flap,mesenchymal stem cells,stem cells,skin flap,ischemia-reperfusion injury,pretreatment,gene modification,biomaterial packaging,joint application".The relevant documents since 2007 were retrieved,and the documents with little relationship between the research content and the article theme,poor quality and outdated content were eliminated through reading the article,and finally 75 documents were included for summary. RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can inhibit inflammatory reactions,resist oxidative stress and induce angiogenesis,which has great potential in the treatment of skin flap ischemia-reperfusion injury.(2)Although mesenchymal stem cells have shown great potential in the treatment of skin flap ischemia-reperfusion injury,their shortcomings in treatment have limited their widespread clinical application.Through pre-treatment(cytokines,hypoxia,drugs,and other pre-treatment mesenchymal stem cells),gene-modified mesenchymal stem cells,biomaterial encapsulation of mesenchymal stem cells,as well as the combined use of mesenchymal stem cells and other drugs or therapeutic methods,can not only overcome the shortcomings of mesenchymal stem cells in treatment,but also improve their therapeutic effectiveness in skin flap ischemia-reperfusion injury.(3)Therefore,further improving the effectiveness of mesenchymal stem cells in treating skin flap ischemia-reperfusion injury and exploring its therapeutic potential are of great significance for the research of mesenchymal stem cells and the treatment of skin flap ischemia-reperfusion injury.

OBJECTIVE To investigate the effect of eukaryotic translation elongation factor 1A1(eEF1A1)on the replication of vesicular stomatitis virus(VSV)and Herpes simplex virus 1(HSV-1)to identify a potential target for broad-spectrum regulation of viruses.METHODS Small interfering RNA(si-eEF1A)was transfected into human skin fibroblasts(BJ-5ta)to inhibit the expression of eEF1A1,and the negative control group was set up.The transfection efficiency was detected by real-time fluo-rescence quantitative PCR(RT-qPCR)and Western blotting,the cell model of eEF1A1 gene silencing was constructed.The cell model was infected with VSV,the gene copy number and protein expression of VSV in the cells were detected.The cell model was infected with HSV-1,the mRNA and protein expres-sion of HSV-1 in the cells were detected.The cell models were transfected with polyinosinic acid[Poly(I:C)]or sodium deoxyribonucleic acid(HT-DNA),respectively.The mRNA expression of interferon-β(IFN-β),C-X-C Motif Chemokine 10(CXCL10)and interferon-stimulated gene 56(ISG56)were detected by RT-qPCR.The phosphorylation expression of interferon regulatory factor 3(IRF3)and TANK binding kinase 1(TBK1)were detected by Western blotting.RESULT Compared with the negative control group,the mRNA and protein expression of eEF1A1 in the eEF1A1 gene silencing group were signifi-cantly decreased(P<0.01),the cell model of eEF1A1 gene silencing was successfully constructed.Compared with the negative control group,the VSV gene copy number of the eEF1A1 gene silencing group decreased by 70%-80%.The VSV protein expression decreased significantly(P<0.01).The mRNA expression of HSV-1 was decreased by 50%-60%,and the protein expression of HSV-1 was significantly decreased(P<0.01).After stimulation with Poly(I:C)or HT-DNA,compared with the negative control group.there was no significant difference in the mRNA expressions of IFN-β,ISG56 and CXCL10 and the protein phosphorylation expression of IRF3 and TBK1 in the eEF1A1 gene silencing group.CONCLUSION eEF1A1 silencing can inhibit VSV and HSV-1 virus replication,suggesting that eEF1A1 has a potential broad-spectrum regulatory effect on RNA viruses and DNA viruses,and may not recog-nize activated immune pathways through intracellular nucleic acid recognition.

The pathogenesis theory of"spleen deficiency and stasis toxin"in gastric cancer holds that spleen is the source of generation and transformation of qi and blood,that spleen deficiency is the internal basis of disease and throughout the disease.Stasis toxin is based on spleen deficiency,which is the fundamental pathogenesis of gastric cancer.In the pathological process of gastric cancer,a variety of metabolic substances in tumor cells and tumor microenvironment,mainly glucose metabolic reprogramming,undergo metabolic changes to reconstruct the phenotype and function of tumor-related macrophages,which is consistent with the pathogenesis theory of"spleen deficiency and stasis toxin".Therefore,this article focused on the reprogramming of glucose metabolism in tumor microenvironment to drive the phenotypic remodeling of tumor-related macrophages,explored the scientific connotation of the pathogenesis theory of"spleen deficiency and stasis toxin"of gastric cancer,and provided references for the theoretical and clinical research on the treatment of gastric cancer by TCM.

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.