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Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.
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Objective To investigate the application value of quantitative parameters MRFDGmax and SUVmax in the stages of hepatitis,liver fibrosis and cirrhosis in rats by whole-body dynamic 18 F-FDG PET/CT Patlak imaging.Methods Twenty-four SD rats were randomly divided into four groups of six rats each,which were the normal group,hepatitis group,liver fibrosis group and cirrhosis group.According to the experimental grouping,rats in each group were induced by the CC14 oil solution complex method.Whole-body dynamic 18 F-FDG PET/CT patlak imaging was performed on each group of rats separately at the completion of induction.After the imaging was com-pleted,the MRFDGmax,SUVmax and CT values of the livers of each group were analyzed;subsequently,the serum of rats in each group was extracted for the detection of liver function indexes(AST,ALT and ALP),and HE staining was performed on the livers of rats in the normal,hepatitis and cirrhosis groups,and Masson staining was performed on those in the liver fibrosis group;the α-SMA expression in the liver tissues of each group was analyzed by immu-nohistochemical method.The data were analyzed by one-way ANOVA,two independent samples t-test and Pearson correlation analysis.Results MRFDGmax,SUVmax values were statistically significant differences among normal,hep-atitis,liver fibrosis and cirrhosis groups(F=84.54,38.35,P＜0.001).The difference in CT values between liver fibrosis and cirrhosis groups was not statistically significant(t=-0.407,P=0.693),and the difference was statistically significant when compared between the rest of the groups(F=112.25,P＜0.001).Compared with the normal group,AST,ALT and ALP of the experimental group showed a staged increase,and the differences were statistically significant(F=93.32,64.63,145.03,P＜0.001).HE staining showed that hepatocytes of the normal group were neatly arranged and structurally intact;a large number of inflammatory cells infiltrated the hepa-titis group with steatosis;pseudo lobe formation was observed in the cirrhosis group.Masson staining of the liver fi-brosis group showed collagen fiber proliferation and thickening of the peritoneum.Immunohistochemistry test results showed that α-SMA expression increased in hepatitis group,liver fibrosis group and cirrhosis group,with a staged increase,and the difference was statistically significant(F=80.57,P＜0.001).Correlation analysis showed a positive correlation between SUVmax and MRFDGmax(r=0.967,P＜0.01).α-SMA was positively correlated with AST,ALT and ALP in the hepatitis,liver fibrosis and cirrhosis groups,respectively(r=0.924,0.756,0.934,P＜0.01).Conclusion Whole-body dynamic 18F-FDG PET/CT Patlak imaging has application value in monitoring hepatitis,liver fibrosis and cirrhosis stages through quantitative parameters MRFDGmax and SUVmax changes.
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The "four-in-one" approach is based on the four-dimensional perspective of "property, position, tendency and syndrome", which helps to identify and analyze classical prescriptions in a multi-dimensional and three-dimensional way. The early pathogenesis of chronic heart failure (CHF) is deficiency of heart Qi and heart Yang and disorder in Qi transformation in triple energizer, while in the later stage of the disease, it progresses from deficiency to excess, with simultaneous occurrence of deficiency and excess syndromes. Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) plays its role in treating chronic heart failure by the four elements of "property, position, tendency and syndrome". Property—Linggui Zhugan Decoction is pungent, sweet, slight sweet and bitter in flavor, but warm in property. The sweet is able to tonify deficiency; the pungent is responsible for dispersing Yang, promoting Qi and draining water retention; the warm nourishes the spleen, raises Yang Qi and resolves phlegm; the bitter could excrete diuresis and dry dampness to guarantee the smooth operation of three energizer. Position-Linggui Zhugan Decoction acts on the heart, spleen and triple energizer. It can stimulate heart Yang, strengthen the spleen, resolve phlegm, and regulate the waterways to promote the Qi transformation in triple energizer. Tendency-The tendency of Linggui Zhugan Decoction is upward and downward in parallel, both internal and external. Warming up and promoting diuresis, raising Yang up and tonifying deficiency, it is conducive to the Yang Qi transformation in triple energizer. Syndrome-Linggui Zhugan Decoction is indicated for the syndrome of heart Yang deficiency and water-fluid retention, which begins with the upper abdomen swelling, Qi rushes against the chest. It is widely used in the treatment of water-vapor impulse heart disease. The disorder of Qi transformation in triple energizer is the main mechanism of recurrent CHF. Linggui Zhugan Decoction can not only warm the fire of Qi transformation in triple energizer, but also smooth the pathway of Qi transformation in triple energizer, which is compatible with the treatment of systemic fluid retention in chronic heart failure. Its pharmacological mechanisms include anti-inflammation, anti-platelet aggregation, regulation of cardiomyocyte cell membrane ion channels, protection against ischemia-reperfusion injury and modulation of vasodilation, etc. Deconstructing Linggui Zhugan Decoction with "four-in-one" approach and discussing its mechanism for treating CHF in combination with the theory of "Qi transformation in triple energizer", have great significance to rejuvenate the vitality of classical prescriptions and to apply them accurately and effectively.
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Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.
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Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.
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Neoantigen pulsed dendritic cell vaccine(Neo-DCVac)is a new type of tumor immunotherapy.Neoantigen is strong immunologic and tumor-specific mutated peptides expressed in a tumor.Neo-DCVac is a therapeutic modality based on the uptake and processing of neoantigens by dendritic cells and their delivery and activation of T cells to trigger the body's immune response for anti-tumor effects.The development of individualized Neo-DCVac based on high-throughput sequencing is expected to be a new direction for precision immunotherapy of tumors.In this review,we discuss construction of individualized Neo-DCVac,clinical application of combination therapy in solid tumors,suitable population for vaccination and the current limitations of Neo-DCVac,aiming to provide a theoretical reference for research on tumor immunotherapy.
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When refractory diarrhea comes on,it greatly affects the life and daily work of patients,and there is no unified treatment.Patients with refractory diarrhea have varying degrees of intestinal flora disorder,so rebuilding the intestinal micro ecosystem may be an effective way to treat refractory diarrhea.Fecal microbiota transplantation(FMT)has the potential to be an effective treatment for refractory diarrhea as a therapy that reconstructs normal intestinal flora.In recent years,FMT has been applied to the treatment of some refractory diarrhea related to intestinal flora imbalance,such as recurrent clostridium difficile infection,inflammatory bowel disease,irritable bowel syndrome,and has achieved good results,but some problems have not been properly solved so far.This article reviews the mechanism of action of FMT in the treatment of refractory diarrhea,its clinical application,research progress and current problems.
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Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.
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The incidence of pediatric otomycosis is gradually increasing, with a widespread prevalence of multidrug-resistant Candida auris.However, its early diagnosis remains challenging, leading to misdiagnosis and underdiagnosis.This review aims to provide a comprehensive overview of pediatric otomycosis based on relevant domestic and international studies.This article reviewed the epidemiology, etiology, risk factors, pathogenic microorganisms, diagnosis, and treatment of pediatric otomycosis, aiming to enhance the understanding of pediatric otomycosis among healthcare professionals.
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Objective To investigate the application value of multimodal MRI in complex anal fistula.Methods The clinical and MRI data of 50 cases with complex anal fistula confirmed by surgery were collected.All patients were examined with 1.5T MR before surgery,including three major modules of conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Finally,the diagnostic efficacy of different MRI modules in complex anal fistula was evaluated based on the surgical results.Results The surgery detected 73 internal orifices,81 external orifices,58 main fistulas,47 branch fistulas and 37 abscesses.Before the surgery,there were 63 internal orifices(86.3%),75 external orifices(92.6%),53 main fistulas(91.4%),40 branch fistulas(85.1%),and 37 abscesses(100%)correctly diagnosed by conventional MRI.Sixty internal orifices(82.2%),75 external orifices(92.6%),51 main fistulas(87.9%),37 branch fistulas(78.7%),and 37 abscesses(100%)were correctly diagnosed by conventional MRI+DWI,while 68 internal orifices(93.2%),78 external orifices(96.3%),56 main fistulas(96.6%),44 branch fistulas(93.6%),and 37 abscesses(100%)were correctly diagnosed by conventional MRI+DCE-MRI.There were 68 internal orifices(93.2%),78 external orifices(96.3%),56 main fistulas(96.6%),44 branch fistulas(93.6%),and 37 abscesses(100%)correctly diagnosed by conventional MRI+DWI+DCE-MRI.Compared with conventional MRI,conventional MRI+DWI or conventional MRI+ DCE-MRI,conventional MRI+DWI+DCE-MRI could find more internal orifices,main fistulas and branch fistulas,and the difference was statistically significant.The multimodal MRI had the highest consistency with the surgical results(Kappa=0.734,P<0.001).Conclusion MRI can accurately estimate the information of internal orifices,external orifices,main fistula,branch fistula and abscess of cases with complex anal fistula.The diagnostic accuracy of multimodal joint application is superior than that of single-modal and dual-modal application.
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Objective:To assess the impact of reducing the mesh density on the overall volume and trueness of single-crown restora-tions.Methods:15 single-crown restorations were included,and their mesh density in 3D software was simplified by 75％,50％,25％,10％and 5％respectively.The overal volume,file size and mesh edge length of the restorations with different reduction levels were compared.Deviation analysis was conducted by curving clipping the area of the shoulder,tissue surface(except for the shoulder)and occlusal surface of the restorations and compared with those of the corresponding regions in the non-simplified restorations.Trueness was assessed using the root mean square(RMS)values for the volume and trueness of different areas.Results:Reducing the mesh den-sity did not significantly affect the overal volume of the single-crown restorations(P＞0.05),but it had a significant impact on the file size(P＜0.001),mesh edge length(P＜0.001)and the trueness of the shoulder(P＜0.001),tissue surface(except for the shoulder)(P＜0.001)and occlusal surface(P＜0.001)areas.Conclusion:Reducing the mesh density had little impact on the overall volume of the restorations but significantly affected their trueness.
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BACKGROUND:Toll-like receptors are an important class of pattern recognition receptors that have important functions in pathogen immunity and cytokine synthesis by recognizing specific molecular patterns.Previous studies have found that different types of bone tissue cells also express Toll-like receptors.Activation or inhibition of Toll-like receptors can have significant effects on osteoblast and osteoclast function through multiple pathways. OBJECTIVE:To summarize the expression and action pathways of Toll-like receptors in osteoblasts and osteoclasts,in order to further elucidate the biological mechanisms involved in the regulation of Toll-like receptors under physiological and pathological conditions. METHODS:Relevant literature was retrieved from databases such as PubMed and CNKI as of December 2022.The Chinese and English search terms included"Toll-like receptor,osteoblast,osteoclast,mesenchymal stem cells,macrophage,cytokine,signaling pathway".According to the research needs,the corresponding criteria were established to screen the final literature. RESULTS AND CONCLUSION:(1)Toll-like receptors could directly regulate osteoblast and osteoclast differentiation through the activation of related signaling pathways.(2)Toll-like receptor activation induces cytokine production and exerts regulatory effects.(3)Toll-like receptor activation can affect the survival and migration ability of osteoblasts and osteoclasts.(4)Toll-like receptors in osteoblasts and osteoclasts are activated in certain diseases and pathological settings and are involved in intercellular interactions.
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BACKGROUND:Studies have shown that posterior cruciate ligament injuries are associated with the anatomical morphology of the knee joint. OBJECTIVE:To explore anatomical morphological risk factors for posterior cruciate ligament injury. METHODS:The imaging data of 142 patients who visited Affiliated Hospital of Binzhou Medical University for knee joint problems from January 2015 to August 2022 were retrospectively analyzed.They were divided into posterior cruciate ligament injury group(n=71,including 49 males and 22 females)and posterior cruciate ligament intact group(n=71,including 49 males and 22 females).Intercondylar notch width,intercondylar notch height,bicondyle width,notch width index,angle of intercondylar notch,Blumensaat's line inlication angle,medial tibial spine height,lateral tibial spine height,tibial spine width,tibiofemoral consistency index,tibial plateau anterior-posterior diameter,medial tibial depth and patellar tendon-tibial shaft angle were measured on MRI images.Posterior tibial slope was measured on X-ray images.The above indicators were included in the logistic regression analysis for investigation. RESULTS AND CONCLUSION:(1)Univariate logistic regression analysis in men showed that tibial spine width,tibiofemoral consistency index,medial tibial depth,and posterior tibial slope were associated with posterior cruciate ligament injury(P<0.05).Multivariate binary logistic regression analysis showed that tibiofemoral consistency index and medial tibial depth were associated with posterior cruciate ligament damage(P<0.05).(2)Univariate logistic regression analysis in women showed that medial tibial spine height,lateral tibial spine height,tibial spine width,and posterior tibial slope were associated with posterior cruciate ligament injury(P<0.05).Multivariate binary logistic regression analysis showed that posterior tibial slope was associated with posterior cruciate ligament damage(P<0.05).(3)The receiver operating characteristic curve showed that tibiofemoral consistency index,medial tibial depth and posterior tibial slope had a certain predictive value on posterior cruciate ligament damage.(4)These findings suggest that anatomical morphological risk factors for posterior cruciate ligament injury differ between men and women,and tibial spine width and posterior tibial slope are common risk factors.In the male population,abnormal tibial spine width,tibiofemoral consistency index,medial tibial depth,and posterior tibial slope are easy to induce posterior cruciate ligament injury.In the female population,abnormal medial tibial spine height,lateral tibial spine height,tibial spine width,and posterior tibial slope are easy to induce posterior cruciate ligament injury.Clinicians can use the above risk factors to identify abnormal knee morphology,assess people at risk of posterior cruciate ligament injury,and provide preventive advice and guidance for treatment.
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BACKGROUND:Tumor necrosis factor-α is a broadly acting inflammatory cytokine that plays an important role in the immune inflammatory response of the body.The current study concluded that tumor necrosis factor-α has significant biological effects on a variety of bone tissue cells. OBJECTIVE:To summarize the expression and action pathways of tumor necrosis factor-α in osteoblastic and osteoclastic cells to further elucidate the regulatory role of tumor necrosis factor-α on bone tissue cells. METHODS:PubMed and CNKI were searched until March 2023,and the Chinese search terms included"tumor necrosis factor α,osteoblast,osteoclast,osteoclast,osteoprogenitor";the English search terms included"TNF-α,osteoblast,osteoclast,osteocyte,osteoprogenitor cell".The corresponding criteria were established according to the research needs,and the final literature was screened.Finally,77 articles were included for review. RESULTS AND CONCLUSION:(1)Tumor necrosis factor-α is participating in regulating the recruitment,appreciation,and differentiation of osteoprogenitor cells,but leads to osteoprogenitor cell stripping and death under specific environments.It also participates in bone resorption directly or indirectly through secreted enzymes.(2)Tumor necrosis factor-α can increase the level of inflammatory factors in the environment by activating relevant signaling pathways in osteoclast lineage cells or directly induce the generation of osteoclasts in specific environments.(3)Tumor necrosis factor-α can inhibit osteogenic differentiation by activating nuclear factor-κB signaling pathway,inhibiting the expression of transcription factors such as RUNX2 and Osterix,and inducing apoptosis and necrotizing apoptosis in osteoblasts.(4)Tumor necrosis factor-α inhibits osteogenesis and promotes osteoclastogenesis by activating the nuclear factor-κB signaling pathway in osteocytes and inducing cytokines such as RANKL,SOST,and DKK1,while enhancing apoptosis of the osteocytes,as well as bone resorption around the apoptotic bone tissue.(5)Taken together,the effect of tumor necrosis factor-α in bone tissue is mainly to inhibit osteogenesis and promote osteoclastosis.The biological effect of tumor necrosis factor-α in bone tissue cells is usually dependent on the activation of tumor necrosis factor receptor and nuclear factor-κB signaling pathways.(6)The interaction of tumor necrosis factor-α with other tissue cell types surrounding bone tissue and its role in bone immune regulation still deserve attention in future studies.
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BACKGROUND:Interleukin-8 is an important cytokine that has been found to play an important role in bone regeneration through multiple pathways. OBJECTIVE:To comprehensively review the action mechanism of interleukin-8 effects on bone regeneration to provide ideas for the following studies on interleukin-8. METHODS:By searching the China National Knowledge Infrastructure database for articles published from January 1999 to February 2023 and PubMed database for articles published from January 1985 to February 2023 reporting the role of interleukin-8 in bone-associated cells and vascularisation.Chinese and English search terms were"interleukin-8,bone repair,bone metabolism,mesenchymal stem cells,osteoblasts,osteoclasts,vascularization".The initial review yielded 508 articles in English and Chinese,and a total of 51 articles were included for review and analysis according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:According to the existing research,interleukin-8 can promote bone cell regeneration and assist bone healing through multiple pathways,which is mainly divided into three aspects:(1)Promote the proliferation and differentiation of bone cells such as mesenchymal stem cells and osteoblasts,and promote the development of cells in the direction of promoting bone healing;(2)interleukin-8 can promote angiogenesis and provide sufficient nutrition and oxygen for bone tissue,thus further improving the quality and stability of bone healing.(3)The appearance of interleukin-8 facilitates the expression of hypoxia-inducible factor-1α,vascular endothelial growth factor,and matrix metalloproteinase,which can create a microenvironment conducive to bone regeneration,thus promoting the regeneration and repair of bone tissue.In summary,interleukin-8 plays an important role in bone healing by promoting osteoblast proliferation and differentiation,facilitating angiogenesis and improving the mechanical properties of bone regeneration,as well as influencing bone metabolism through osteoclasts,mesenchymal stem cells,and other action sites.
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BACKGROUND:Careful regulation of bone immune response during repair of bone scaffold is important for bone regeneration. OBJECTIVE:To review the influence of bone immune response on bone repair and the design of bone tissue engineering scaffold with regulating bone immune function and its application in bone repair. METHODS:Relevant articles published from 1973 to 2023 were retrieved from Science Direct,PubMed,Web of Science,and CNKI databases.English search terms were"osteoimmunology,macrophages,bone repair materials,bone scaffold,bone defects,bone regeneration".Chinese search terms were"bone immunity,macrophages,bone repair material,bone stent,bone defect,bone regeneration".Totally 80 articles of the latest research progress in this field were summarized and analyzed. RESULTS AND CONCLUSION:(1)A detailed review was conducted on the important time points in the origin and development process of bone immunity,and it was explained that macrophages,as important members of the bone immune regulatory system,can be divided into two phenotypes:M1(pro-inflammatory)and M2(anti-inflammatory),and play a key role in different stages of bone regeneration.During the inflammatory phase,M1 type macrophages can activate osteoclasts,initiate tissue repair processes,and participate in the reconstruction of bone microvascular networks.On the other hand,during the bone tissue regeneration process in the later stages of inflammation,sustained high expression of M1 type macrophages can hinder the formation of new bones.During the repair phase,M2 macrophages can secrete osteogenic cytokines,stimulate osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells,and promote bone formation.On the other hand,long-term activation of M2 macrophages can increase the secretion of fibrogenic molecules,leading to excessive formation of scar tissue and delaying the healing process.Therefore,regulating macrophages to undergo phenotype transformation at appropriate stages and constructing an immune microenvironment beneficial for osteogenesis has great significance for bone regeneration.(2)In the process of designing bone scaffolds with bone immune regulation characteristics,the physical and chemical properties such as scaffold roughness,pore structure,stiffness,hydrophilicity,surface charge,and surface functional groups can be changed to affect non-specific protein and cell adhesion,thereby affecting the interaction between bone scaffolds and the immune system.By designing surface functional coatings of bioactive substances such as hydroxyapatite,bioactive glass,metal ions,extracellular matrix,drugs,cytokines,and exosomes,the immune microenvironment can be actively regulated by releasing bioactive substances after implantation into the body,affecting macrophage polarization and crosstalk between macrophages and bone cells,and promoting more M2 polarization of macrophages,so as to build a bone immune microenvironment that is conducive to bone regeneration.(3)Based on the research and development of bone tissue engineering scaffolds,in addition to focusing on the direct regulatory factors of stem cell osteogenic differentiation,this article also proposes that attention should be paid to the management of the immune microenvironment of stem cell differentiation.By regulating the appropriate bone immune microenvironment,more stem cell osteogenic differentiation can be induced;the osteogenic efficiency of the scaffold can be enhanced,and the concept of"bone immune regulatory characteristics"can be condensed;deeply elucidated the multi-directional regulatory role of the bone immune microenvironment and introduced the existing strategies for changing the physicochemical properties and surface functional coating of scaffolds to endow them with bone immune regulatory potential,providing new ideas for guiding the development of a new generation of bone tissue engineering scaffolds with bone immune regulatory characteristics.However,the bone immune microenvironment is a dynamic equilibrium state,and most of the existing regulatory strategies do not consider the dynamic matching of regulation.Therefore,the research and development of intelligent bone immune regulatory scaffolds with efficient and targeted regulation of the immune microenvironment will be a key focus of attention for scholars in future.
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Objective:To explore the application effect of 5A self-management support method in the management of patients with stroke.Methods:A 5A self-management support program for stroke patients was developed from the five dimensions of Ask,Advice,Assess,Assist and Arrange.A total of 75 stroke patients admitted to the Neurology Department of Beijing Shijitan Hospital from November 2020 to April 2021 were randomly selected and divided into a control group(38 cases)and an observation group(37 cases)according to different intervention methods.The control group adopted routine intervention method,the observation group adopted 5A self-management support method.The intervention time expired 3 months after the patient was discharged.The intervention effects of the two groups were evaluated from the scores of self-management behavior,self-efficacy,activities of daily living and depression and anxiety situation.Results:At the end of the third month after discharge,the self-management behavior and self-efficacy scores for weekly exercise time,cognitive symptom management,communication with doctors,symptom management self-efficacy and disease common management self-efficacy scores of patients in the observation group scored(180.92±102.38),(3.68±1.32),(3.29±1.41),(7.15±3.44)and(6.82±2.10),respectively,which were significantly higher than those of the control group,the differences were statistically significant(t=5.63,4.10,4.37,6.40,7.60,P<0.05).At the end of the third month after discharge,the modified Barthel index(MBI)score of the patients in the observation group was(68.06±12.80),which was significantly higher than that of control group,the difference was statistically significant(t=7.27,P<0.05);the depression and anxiety scores of patients in the observation group were lower than those of the control group,the difference was statistically significant(t=2.38,2.64,P<0.05).Conclusion:The 5A self-management support method can significantly improve the self-management behavior and the ability of daily living activities of stroke patients after discharge,and effectively improve the anxiety and depression of patients,and improve the self-management effect of stroke patients after discharge.
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Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
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Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.
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Objective:To investigate the role of circular RNA (circRNA) circSEPT9 in the radioresistance of glioma and its molecular mechanism.Methods:Pathological samples were collected from 40 glioma patients who underwent surgery and postoperative radiotherapy in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2022. All patients were divided into the radiation-sensitive and radiation-resistant groups. The expression levels of circSEPT9 were assessed using real-time reverse transcription PCR (RT-qPCR) in two groups. The radiation-resistant glioma cell U251R was constructed based on human glioma cell U251. The U251R cells were divided into the negative control (si-NC), circSEPT9 knockdown (si-circSEPT9), negative control combined with irradiation (si-NC+4 Gy), circSEPT9 knockdown combined with irradiation (si-circSEPT9+4 Gy), circSEPT9 knockdown combined with control inhibitor and irradiation (si-circSEPT9+NC inhibitor+4 Gy), and circSEPT9 knockdown combined with miR-432-5p inhibitor and irradiation (si-circSEPT9+miR-432-5p inhibitor+4 Gy) groups. The targeting relationship between circSEPT9 and miR-432-5p was verified through dual-luciferase reporter assay. Colony formation assay was employed to assess the survival rate of U251R cells. Flow cytometry was adopted to measure the apoptosis rate. The expression level of circSEPT9 in glioma tissues was statistically analyzed using independent sample t-test. The survival and apoptosis rates in each group were evaluated using one-way ANOVA. Results:The expression level of circSEPT9 was up-regulated in the glioma tissues of patients in the radiation-resistant group (1.00±0.18 vs. 3.25±0.13, P<0.05). Compared to the si-NC group, the U251R cells in the si-circSEPT9 group exhibited a significant reduction in survival fraction and a notable increase in apoptosis rate (9.24±0.83 vs. 19.36±2.13, both P<0.05). After radiation exposure at 4, 6 and 8 Gy, si-circSEPT9 treatment significantly decreased the survival fraction in U251R cells (all P<0.05). Compared with the si-NC+4 Gy group, the apoptosis rate was increased in the si-circSEPT9+4 Gy group (18.83±1.94 vs. 35.23±3.56, P<0.05). Dual-luciferase reporter assay showed that circSEPT9 could target and negatively regulate the expression level of miR-432-5p. Compared with the si-circSEPT9+NC inhibitor+4 Gy group, the survival fraction of U251R was significantly increased in the si-circSEPT9+miR-432-5p inhibitor+4 Gy group ( P<0.05). Conclusion:Knockdown of circSEPT9 enhances the radiosensitivity of glioma cells by regulating cell apoptosis through targeting the miR-432-5p.