The vasculature plays a critical role in homeostasis and health as well as in the development and progression of a wide range of diseases, including cancer, cardiovascular diseases, metabolic diseases (and their complications), chronic inflammatory diseases, ophthalmic diseases, and neurodegenerative diseases. As such, the growth of the vasculature mediates normal development and physiology, as well as disease, when pathologically induced vessels are morphologically and functionally altered owing to an imbalance of angiogenesis-stimulating and angiogenesis-inhibiting factors. This review offers an overview of the angiogenic process and discusses recent findings that provide additional interesting nuances to this process, including the roles of intussusception and angiovasculogenesis, which may hold promise for future therapeutic interventions. In addition, we review the methodology, including those of in vitro and in vivo assays, which has helped build the vast amount of knowledge on angiogenesis available today and identify important remaining knowledge gaps that should be bridged through future research.
Animals ; Signal Transduction/physiology* ; Humans ; Neovascularization, Pathologic/physiopathology* ; Neovascularization, Physiologic/physiology* ; Models, Animal ; Angiogenesis

Objective To construct risk prediction models of death or readmission in patients with acute heart failure(AHF)during the vulnerable phase based on machine learning algorithms and screen the optimal model.Methods A total of 651 AHF patients with admitted to Department of Cardiology of the Second Affiliated Hospital of Army Medical University from October 2019 to July 2021 were included.The clinical data consisting of admission vital signs,comorbidities and laboratory results were collected from electronic medical records.The composite endpoint was defined as all-cause death or readmission for worsening heart failure within 3 months after discharge.The patients were divided into a training set(521 patients)and a test set(130 patients)in a ratio of 8:2 through the simple random sampling.Six machine learning models were developed,including logistic regression(LR),random forest(RF),decision tree(DT),light gradient boosting machine(LGBM),extreme gradient boosting(XGBoost)and neural networks(NN).Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical benefit of the models.Shapley additive explanation(SHAP)was used to explain and evaluate the effect of different clinical characteristics on the models.Results A total of 651 AHF patients were included,of whom 203 patients(31.2%)died or were readmitted during the vulnerable phase.ROC curve analysis showed that the AUC values of the LR,RF,DT,LGBM,XGBoost and NN model were 0.707,0.756,0.616,0.677,0.768 and 0.681,respectively.The XGBoost model had the highest AUC value.DCA showed that the XGBoost model exhibited greater clinical net benefit compared with other models,with the best predictive performance.SHAP algorithm analysis showed that the clinical features that had the greatest impact on the output of the model were serum uric acid,D-dimer,mean arterial pressure,B-type natriuretic peptide,left atrial diameter,body mass index,and New York Heart Association(NYHA)classification.Conclusion The XGBoost model has the best predictive performance in predicting the risk of death or readmission of AHF patients during the vulnerable phase.

ObjectiveTo analyze and determine the differential components of freeze-dried and sun-dried Panacis Quinquefolii Radix（PQR）， and to compare the differences in their pro-angiogenic activities. MethodFingerprints of freeze-dried and sun-dried PQR were established based on ultra performance liquid chromatography（UPLC）， and chemometrics methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to determine the differential saponin composition of the two decoction pieces， and six representative saponins were selected and their contents in freeze-dried and sun-dried PQR were determined by UPLC. Transgenic zebrafish line Tg（fli1a∶EGFP） embryos fertilized for 24 h were selected， and different doses of 70% methanol extracts of freeze-dried and sun-dried PQR（10， 30 mg·L^-1） were used to intervene in normal zebrafish and in a zebrafish model of intersegmental vascular（ISV） injury induced by vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（PTK787）， then the development of subintestinal vein（SIV） and ISV of zebrafish was observed， SIV diameter， mean number of crossings and mean number of germinations were determined， and the ISV vascular index was calculated， in order to compare the pro-angiogenic activities of the two decoction pieces. ResultThe similarity of the fingerprints of freeze-dried and sun-dried PQR decoction pieces was>0.950， and 17 common peaks were identified， of which 6 common peaks were designated as peak 6（ginsenoside Rg₁）， peak 7（ginsenoside Re）， peak 8（ginsenoside Rb₁）， peak 11（ginsenoside Rc）， peak 13（ginsenoside Rb₂）， and peak 16（ginsenoside Rd）， respectively. A total of 11 differential saponin components were screened by PCA and OPLS-DA， indicating that there were some differences in the contents of the components in the two decoction pieces. The results of determination showed that the contents of ginsenosides Rg₁， Re， Rb₁ and Rb₂ in freeze-dried PQR were higher than those in sun-dried PQR， while the contents of ginsenosides Rc and Rd were lower than those in sun-dried PQR（P<0.05， P<0.01）. In the study of the pro-angiogenic effect on normal zebrafish embryos， compared with the blank group， and the SIV vessel diameter， mean germination rate and mean crossover rate were significantly higher in the high-dose groups of freeze-dried and sun-dried PQR（P<0.01）， and the vessel diameter， mean numbers of crossings and germinations in the freeze-dried PQR group were higher than those of the sun-dried PQR group（P<0.05）. In the study of the pro-angiogenic effect on zebrafish embryos with ISV injury， the development of ISV in the model group was significantly inhibited when compared with the blank group， compared with the model group， different dose groups of freeze-dried and sun-dried PQR could promote the growth and sprouting of ISV， and the number of normal blood vessels in the freeze-dried PQR group was significantly higher than that in the sun-dried PQR group at the same dosage（P<0.05）. ConclusionFreeze-drying can effectively avoid the loss and secondary transformation of ginsenosides in PQR， and its angiogenic activity is better than that of sun-dried PQR， which can provide a reference for the production and development of high-quality PQR decoction pieces.

Anti-angiogenic drugs (AADs), which mainly target the vascular endothelial growth factor-A signaling pathway, have become a therapeutic option for cancer patients for two decades. During this period, tremendous clinical experience of anti-angiogenic therapy has been acquired, new AADs have been developed, and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy. However, improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required. This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development. We revisit the history of concept initiation and AAD discovery, and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

Knee osteoarthritis(KOA)is a chronic degenerative joint disease which could result disabling in late stage.The objectivity in imaging diagnosis of KOA is often various due to human factors and other influences.Artificial intelligence(AI)has been proved highly valuable for KOA.The progresses of AI in imaging diagnosis and grading of KOA,detecting cartilages lesions,predicting pain and long-term care of KOA were reviewed in this article.

Objective:To design a multi-epitope antigen of norovirus(NoV)based on bioinformatics technology and to pre-pare and characterize it.Methods:Bioinformatics methods were used to construct and analyze the NoV multi-epitope antigen NoV-ZH.Recombinant proteins were prepared and characterized by prokaryotic expression system,and monoclonal antibodies were prepared by animal immunization and hybridoma technology,and initially applied in colloidal gold platform.Results:The designed multi-epitope antigen had a large proportion of random curls in the secondary structure,with theoretical molecular mass and isoelectric point(PI)of 13.1 ku and 7.16,which were stable and hydrophilic.It had good immunogenicity and could activate humoral and cellular immune re-sponses.The proteins prepared by ligating pET-28a(+)and pET-32a vectors with antigenic sequences were expressed as inclusion body proteins and soluble proteins,respectively.A pair of paired antibodies was obtained by animal immunization and hybridoma tech-nique,and applied to colloidal gold test strips with a sensitivity of 0.5 ng/ml,and the test strips could specifically bind two genotypes of NoV recombinant capsid proteins.Conclusion:The successful preparation and characterization of multi-epitope antigen of norovirus provides a reference for the subsequent exploration of NoV universal detection targets and the development of diagnostic raw materials.

This study aims to establish a time-resolved fluorescence immunochromatography method for simultaneous determination of human papillomavirus (HPV) type 16 E6 and L1 protein concentrations. The amount of lanthanide microsphere-labeled antibodies, the concentration of coated antibodies, and the reaction time were optimized, and then a test strip for the simultaneous determination of the protein concentrations was prepared. The performance of the detection method was evaluated based on the concordance of the results from clinical practice. The optimal conditions were 8 μg and 10 μg of HPV16 L1 and E6-labeled antibodies, respectively, 1.5 mg/mL coated antibodies, and reaction for 10 min. The detection with the established method for L1 and E6 proteins showed the linear ranges of 5-320 ng/mL and 2-64 ng/mL and the lowest limits of detection of 1.78 ng/mL and 1.09 ng/mL, respectively. There was no cross reaction with human immunodeficiency virus (HIV), treponema pallidum (TP), or HPV18 E6 and L1 proteins. The average recovery rate of the established method was between 97% and 107%. The test strip prepared in this study showed the sensitivity, specificity, and diagnostic accuracy of 97.46%, 90.57%, and 95.32%, respectively, in distinguishing patients with cervical cancer and precancerous lesions from healthy subjects, with the area under the curve (AUC) of 0.980 1 and 95% Confidence Interval (CI) of 0.956 5 to 1.000 0. The time-resolved fluorescence immunochromatography combined with the test strips prepared in this study showed high sensitivity, high accuracy, simple operation, and rapid reaction in the quantitation of HPV16 E6 and L1 proteins. It thus can be used as an auxiliary method for the diagnosis and early screening of cervical cancer and precancerous lesions and the assessment of disease course.
Oncogene Proteins, Viral/immunology* ; Humans ; Chromatography, Affinity/methods* ; Female ; Human papillomavirus 16 ; Repressor Proteins/immunology* ; Capsid Proteins/immunology* ; Papillomavirus Infections/diagnosis* ; Fluorescence ; Uterine Cervical Neoplasms/virology*

Cerebral hemorrhage accounts for about 10%-15% of all strokes， and its pathogenesis is complex. Currently， the main clinical treatment is mainly medical symptomatic treatment， including the use of antihypertensive drugs， hypoglycemic drugs， and hemostatic drugs， and surgical treatment is required in some cases， but there is still a lack of effective treatment. In recent years， traditional Chinese medicine and proprietary Chinese medicine have been widely accepted for their stable efficacy， high safety， and low cost. Rhei Radix et Rhizoma is one of the most commonly used herbal medicines for the treatment of cerebral hemorrhage. This paper summarizes the relevant literature on the treatment of cerebral hemorrhage with Rhei Radix et Rhizoma and finds that its active ingredients are mainly anthraquinones， such as emodin， Rhei Radix et Rhizoma acid， and Rhei Radix et Rhizoma phenol. The herbal formulas are Da Chengqitang， Shengdi Dahuangtang， Liangxue Tongyufang， and Naoxueshu oral liquid. The effects involve protecting the blood-brain barrier， promoting hematoma absorption， reducing inflammation levels， decreasing lactic acid accumulation at the bleeding site， and increasing the expression of brain-derived neurotrophic factors. The pathways involved include aquaporin 4 （AQP4）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB）， nuclear factor E₂-related factor 2 （Nrf2）， and Wnt3a/β-linked protein pathway. This paper summarizes the progress of clinical studies and animal experiments on the treatment of cerebral hemorrhage with active ingredients of Rhei Radix et Rhizoma and herbal compounds containing Rhei Radix et Rhizoma， so as to provide a reference for the treatment protocol of cerebral hemorrhage.

With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.

Objective:To evaluate the safety and efficacy of rubber band and clip facilitated endoscopic submucosal dissection (RAC-ESD) for colorectal neoplasms.Methods:A retrospective cohort study was performed. Clinical data of 115 patients with colorectal neoplasm receiving ESD from September 2018 to August 2019 were retrospectively analyzed. Thirty-four patients received RAC-ESD treatment (RAC-ESD group) and 81 received conventional ESD treatment (conventional ESD group). The procedure time, the dissected area per minute during ESD, en bloc resection rate, complete resection rate, curative resection rate, complication occurence and recurrence rate were compared between the two groups.Results:The median specimen area of RAC-ESD group was 6.32 (7.53) cm 2, and the median procedure time was 40.0 (55.0) min. The mean dissected area per minute was 0.14 (0.20) cm 2/min. While in conventional ESD group, the median specimen area was 4.71 (5.02) cm 2, the median procedure time was 50.0 (50.0) min and the mean dissected area per minute was 0.09 (0.07) cm 2/min. The median specimen area of RAC-ESD group was slightly larger and the median procedure time was slightly shorter than those of conventional ESD group, but neither was significantly different(both P>0.05). The median dissected area per minute of RAC-ESD group was significantly larger than that of the conventional ESD group ( P=0.008). The en bloc resection rate, complete resection rate and curative resection rate of RAC-ESD group were 100.0% (34/34), 100.0% (34/34) and 97.1% (33/34), while those of the conventional ESD group were 100.0%(81/81), 96.3%(78/81) and 91.4%(74/81), respectively. There was no ESD-related complication in either group. After 10.0±5.5 months of follow-up, there was no local recurrence in both groups. Conclusion:RAC-ESD may increase resection efficacy with safety.