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

OBJECTIVES: To evaluate the one-year outcomes of valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) using SAPIEN 3 valve for treating mitral bioprosthetic valve failure. METHODS: A retrospective analysis was conducted on 26 patients with mitral bioprosthetic valve failure who underwent ViV-TMVR at West China Hospital, Sichuan University, between November 2022 and July 2024. The age of patients was 71.5 (64.5, 74.5) years, and 69.2% were female. Bioprosthetic valve failure occurred at (9.7±3.7) years after initial surgical implantation, with the most common failure mode being mixed stenosis and regurgitation (53.8%). The SAPIEN 3 valve was implanted via either a transseptal or transapical approach. Echocardiography was performed preoperatively, immediately post-procedure, and at 1 month, 6 months, and 1 year post-procedure. Outcomes included all-cause mortality, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score, and postoperative complications. RESULTS: The procedure was performed via the transseptal approach in 21 patients (80.8%) and the transapical approach in 5 patients (19.2%). All procedures were technically successful. No paravalvular leakage was observed immediately post-procedure, and mitral valve hemodynamics improved significantly. At the 1-year follow-up, 2 patients had died. Two patients (8.3% of survivors) were of NYHA functional class Ⅲ, and KCCQ-12 score improved to (88.4±14.6) points (both P<0.01). Echocardio-graphy at 1 year postoperatively showed significant reductions in peak mitral valve velocity [to (2.29±0.32) m/s] and mean transvalvular pressure gradient [to (9.5±3.5) mmHg, 1 mmHg=0.133 kPa] compared to baseline (both P<0.05). No moderate or severe mitral regurgitation or paravalvular leakage was observed. The proportion of patients with moderate-to-severe pulmonary hypertension decreased from 65.4% preoperatively to 13.0% at 1 year (P<0.05). CONCLUSIONS ViV-TMVR with the SAPIEN 3 valve for mitral biopro-sthetic valve failure is associated with high procedural success, significantly improved valve hemodynamics of the mitral value, alleviation of pulmonary hypertension, enhanced quality of life, and a low rate of complications at 1 year after the operation.
Humans ; Female ; Male ; Retrospective Studies ; Aged ; Bioprosthesis ; Heart Valve Prosthesis ; Mitral Valve/surgery* ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Prosthesis Failure ; Treatment Outcome ; Mitral Valve Insufficiency/surgery*

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.

AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.

AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.

Objective:To explore the effect of identifying pelvic lymph nodes by different injection of indocyanine green (ICG) during fluorescent laparoscopic radical cystectomy.Methods:The data of 54 male bladder cancer patients admitted to the First Hospital of Shanxi Medical University from September 2021 to September 2022 were analyzed. Preoperative cystoscopic biopsy all revealed a pathological diagnosis of urothelial carcinoma. All patients underwent fluorescent laparoscopic radical cystectomy plus pelvic lymph node dissection.They were divided into 3 groups according to the annotated route: 6 in the medial malleolus injection group, 68(61, 73) years; 4 in the perineal injection group, 67(59, 74) years; 44 in the medial malleolus and perineum, 64(45, 78) in the combined injection group. Under general anesthesia, patients were placed in the supine position with 0.3 to 0.5 ml of subcutaneous ICG solution (2.5 mg/ml) injected from 1.0 to 1.5 h before surgery. In the medial malleolus injection group, 0.3 to 0.5 ml (0.75 mg/place) was injected at 2 cm above the medial malleolus and 0.3 to 0.5 ml (0.75 mg/place) at two symmetrical sites above the anus. Intraoperatively, 4K fluorescent laparoscopy was used to observe the color development of the injection site and lymphatic vessels in vitro, and then to observe the development of pelvic lymph nodes in vivo.Results:In 3 groups, inguinal lymph nodes were developed about 30 min after ICG injection, and 1 h later, the longest (4.5±0.3) h. The external iliac and common iliac lymph nodes, the obturatorius lymph nodes in the perineal injection group, and the inguinal, obturatorius, external iliac, internal, anterior sacral, and common iliac lymph nodes in the medial malleolar and perineal injection group. In this study, in 54 cases, the postoperative pathological examination confirmed that the removed fluorescently labeled tissue was lymph node tissue, and the lymph node detection rate was 100%. The postoperative stage was pT 2, 14, 32 pT 3 and 8 pT 4; 4 pNx, 44 pN 0, 5 pN 1and 1 pN 2. In the medial malleolar injection group, 2 patients staged pT 2, 3 stage pT 3, 1 stage pT 4; 1stage pNx stage, 4 stage pN 0 and 1 stage pN 1 stage. In the perineal injection group, 4 patients had postoperative pathological stage pT 3N 0; in the medial malleolar and perineal injection group, 12 pT 2, 25 and 7 pT 3; 3 pNx, 36 pN 0, 4 pN 1 and 1pN 2. Conclusions:ICG injection through the perineum and subcutaneous labeling of pelvic lymph nodes, and the simple malleolus or perineal injection can not completely develop the pelvic lymph nodes. The combined injection could fully develop the pelvic lymph nodes, which may accurately guide the operator to locate, identify and remove pelvic lymph nodes.

The incidence of ischemic stroke in the pregnancy is low and the mortality is high. The clinical and imaging data of a pregnant woman with atrial septal defect complicated with stroke after awakening were reviewed to explore the imaging manifestations, pathogenesis and treatment strategy of pregnancy-related stroke. The aim of this study was to improve the understanding of acute stroke in pregnant women with atrial septal defect, and to provide reference for clinical diagnosis and treatment.

Objective:To understand the characteristics of sexualized drug use (SDU) among men who have sex with men (MSM) in Chengdu and classify their behavioral patterns by applying the two-step cluster (TSC) algorithm and by exploring the association between SDU patterns and high risk sexual behaviors, in order to provide a reference basis for the development of HIV prevention interventions.Methods:Supported by an MSM-friendly organization in Chengdu from December 2021 to February 2022, MSM were recruited by on-site survey and peer referral to collect information on sociodemographics, SDU characteristics, sexual behaviors, STD diagnosis, and HIV status. TSC was performed to classify the characteristics of SDU, and the differences between groups were compared. Chi-square test and multiple binary logistic regressions were used to identify the relationship between SDU clusters and HIV-related risk sexual behaviors.Results:A total of 727 MSM were surveyed, and 39.8% (289/727) of the respondents reported SDU experience with a same-sex partner in the last six months. TSC clustered SDU-MSM into three behavioral pattern groups. There were significant differences in monthly income, types of drugs used for SDU, mode, frequency, polydrug use, multiple sexual partners, non-adherence to condom use, and group sex among the three groups of SDU-MSM ( P<0.05). Multivariate binary logistic regression analysis showed that the third category of SDU-MSM was 2.22 (95% CI: 1.06-4.66) times more likely than the first category not to use condoms consistently; the third and second categories were 2.82 (95% CI: 1.18-6.77) times and 8.78 (95% CI: 3.42-22.42) times. Conclusions:The prevalence of SDU among MSM in Chengdu was more than 1/3, and different SDU clustering pattern was associated with high-risk sexual behaviors. MSM with higher SDU frequency, drug use, and polydrug abuse are more difficult to adhere to condom use and more likely to have group sex and high risk sexual behaviors, increasing the risk of STD and HIV infection, and need to strengthen SDU surveillance and intervention.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Thyroid cancer(TC)is an inert tumor,with a high proportion of patients undergoing lymph node metastasis(LNM),and a high recurrence rate after metastasis,resulting in a poor clinical prognosis.The key to solving this problem is to find non-invasive biomarkers with high specificity.Extracellular vesicles play a crucial role in intercellular communication and epigenetic regulation by transporting genetic material.TC tumor cells can transfer genetic information to the tumor microenvironment through miRNA in exosomes,changing the surrounding microenvironment into an environment suitable for tumor growth,thereby promoting pro-liferation and migration of TC.This article will review the role and application prospects of extracellular miRNAs in the early diagnosis of TC metastasis in recent years,to provide a reference for exploring biomarkers of TC.