The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

Objective:To explore the effects of parathyroid hormone(PTH)on the osteogenic differentiation of osteoblasts by reg-ulating macrophage polarization in inflammatory microenvironment.Methods:Macrophages were pretreated with lipopolysaccharide(LPS)for 2 h to establish an inflammatory microenvironment model,and then treated with PTH for 24 h.Macrophages and osteo-blasts were co-cultured in Transwell cells.Alkaline phosphatase staining,alizarin red staining,RT-qPCR and Western blot were applied to detect osteogenic differentiation.The expression of SOCS1/JAK2/STAT3 protein in macrophages was detected by West-ern blot.The change of STAT3 expression was detected after adding AG490.The expression of miR-155-5p,SOCS1,IL-1β,IL-6 and i-NOS was detected by ELISA and RT-qPCR.Results:LPS induced M1-type polarization of macrophages and inhibited the osteogenic differentiation of osteoblasts.PTH inhibited the polarization of M1-type macrophages and promoted the osteogenic differ-entiation of osteoblasts in inflammatory microenvironment(P＜0.05).PTH down-regulated the expression of miR-155-5p,IL-1β,IL-6,i-NOS,p-JAK2/JAK2 and p-STAT3/STAT3 in macrophages under inflammatory microenvironment(P＜0.05),and up-reg-ulated SOCS1(P＜0.05).AG490 further inhibited p-STAT3/STAT3 expression.Conclusion:PTH inhibits the polarization of M1-type macrophages and promotes osteogenic differentiation of osteoblasts by down-regulating miR-155-5p and then targeting SOCS1/JAK2/STAT3 signaling pathway in inflammatory microenvironment.

BACKGROUND:Neuropilin 1 plays a critical role in fracture healing,especially in osteogenesis-angiogenesis coupling. Osteogenesis-coupled angiogenesis is vital for fracture healing,including angiogenesis and bone formation (especially H-type vessel formation) and their association. OBJECTIVE:To review the research progress of neuropilin 1 in promoting osteogenesis-coupled angiogenesis during fracture healing.METHODS:The literature search was performed in the PubMed and Chinese National Knowledge Infrastructure databases for articles published from January 1982 to April 2024 using the search terms "Neuropilin-1,neuropilin 1,NRP1,neuropilin-1,NRP-1,Neuropilin 1,Nrp1,Nrp-1." We identified 43 articles associated with fracture healing,H-type vessels,arteries,bone cells,and angiogenesis-osteogenesis coupling. Moreover,24 articles were searched manually. Finally,67 papers were included.RESULTS AND CONCLUSION:(1) Angiogenesis,osteoblastogenesis,and their association were critical for angiogenesis-osteogenesis coupling during fracture healing. Especially H-type vessel formation was critical during fracture healing. H-type vessels consisted of endothelial cells and pericytes. Osteoblasts,osteoclasts,chondrocytes,and other skeletal cells were critical contributors to new bone formation. (2) Neuropilin 1 enhanced endothelial cell migration and stabilization,increased stability of endothelial cells and pericytes,and strengthened the link of endothelial cells and pericytes to initiate angiogenesis by vascular endothelial growth factor and platelet-derived growth factor. (3) Neuropilin 1 promoted bone regeneration by suppressing osteoclastogenesis and enhancing osteoclasts and chondrocyte formation. (4) Neuropilin 1 was a key factor in angiogenesis-osteogenesis coupling. (5) Topical application of neuropilin 1 and relative biologics,and combination neuropilin 1,nano drug-loading systems,and polymerized smart materials provided a new idea for treatment of fractures and hold great promise for extensive applications.

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.

Objective To elucidate the effects and mechanisms of Biejiajian pill(BJJP)-containing serum on the malignant biological behaviors of hepatocellular carcinoma Huh7 cells.Methods This research knocked down CKLF-like MARVEL transmembrane domain containing 6(CMTM6)expression using a CMTM6-specific small interfering RNA(siRNA).Healthy Sprague-Dawley rats were used to prepare normal rat serum and low-(0.55 g/kg),medium-(1.1 g/kg),and high-(2.2 g/kg)BJJP-containing.Huh7 cells were cultured with normal fetal bovine serum(BC),normal rat serum(NC),and low-,medium-,and high-dose BJJP serum(LBJJP,MBJJP,and HBJJP,respectively).BJJP-containing serum and si-CMTM6 were applied to Huh7 cancer cells,and the proliferation,migration,and invasion abilities were evaluated by CCK-8 and Transwell assays,respectively.Protein expression levels of proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)markers,and CMTM6 were detected by Western blot.Results CMTM6 knockdown significantly reduced the mRNA and protein expression level of CMTM6 in Huh7 cells(P＜0.05).There were no significant differences between the BC and NC groups in terms of cell proliferation,migration,invasion,expression levels of PCNA,EMT markers,and CMTM6(all P＞0.05).BJJP-containing serum markedly inhibited Huh7 cell proliferation,migration,and invasion(P＜0.05),downregulated PCNA,CMTM6,N-cadherin,and Vimentin expression,and upregulated E-cadherin compared with the NC group(all P＜0.05).CMTM6 knockdown suppressed malignant behaviors,with reduced PCNA,Vimentin,and N-cadherin and elevated E-cadherin expression(all P＜0.05).Conclusions BJJP-containing serum can significantly inhibit Huh7 cell growth,invasion,migration,and EMT progression,potentially mediated via CMTM6 suppression.

Objective:This study aims to investigate the differences between two groups of patients treated with nucleos（t）ide analogues（NAs）：those with undetectable HBV DNA by ultrasensitive testing and those with HBV DNA below the quantification limit. The findings will provide a basis for the clinical interpretation and rational use of ultrasensitive HBV DNA results.Methods:This cross-sectional study included patients with chronic HBV infection who were treated with NAs between May 2023 and December 2023 at the outpatient clinic and inpatient department of the Hepatology Department，The Second Hospital of Shandong University. All patients had ultrasensitive HBV DNA results that were either undetectable or less than 20 IU/ml. The group with undetectable ultrasensitive HBV DNA was defined as the target not detected（TND）group，while the group with HBV DNA levels below 20 IU/ml was defined as the limit of quantitation（LOQ）group. Data on patients' sex，age，type of NAs used，routine blood tests，liver and kidney function，quantitative hepatitis B serology，ultrasensitive HBV DNA，HBV pregenomic RNA（pgRNA），abdominal ultrasound，CT or MRI imaging were collected. Differences between the two groups in terms of demographic data and HBV markers were analyzed.Results:A total of 827 patients were included in the study，with 536 patients in the TND group and 291 in the LOQ group. Compared with the TND group，the LOQ group had a younger age（ P<0.001），and higher level of ALT，AST，HBeAg positive rate，HBsAg，and HBV pgRNA（all P<0.001）. Subgroup analyses stratified by HBeAg status，cirrhosis status，and sex showed that the LOQ group had significantly higher levels of HBsAg and HBV pgRNA compared to the TND group in all subgroups（all P<0.05）. Conclusion:The LOQ group had significantly higher levels of HBsAg and HBV pgRNA compared to the TND group.

Objective:To explore advantages of CT and MRI imaging in clinical assessment of specific indicators (trochlear dysplasia and tibial tubercle lateralization) of acute patellar dislocation in adolescents by comparing CT versus MRI imaging.Methods:A retrospective study was conducted to analyze the CT and MRI imaging data of 73 patients with acute patellar dislocation who had been admitted to Department of Orthopedics, The Second Hospital of Tangshan from January 2014 to September 2024. There were 37 males (21 left knees and 16 right knees) and 36 females (19 left knees and 17 right knees), with a mean age of 15 (13, 16) years. On MRI images, the distance between the patellar tendon-trochlear groove (PT-TG) was measured. On CT images, the distance between the tibial tuberosity-trochlear groove (TT-TG) was measured. Additionally, the distance from the tibial tubercle-Roman arch (TT-RA), the sulcus angle (SA), the trochlear depth (TD), the lateral trochlear inclination (LTI), and the trochlear facet asymmetry (TFA) were measured on both MRI and CT images.Results:The TT-TG measured on CT [(20.47±4.42) mm] was significantly greater than that on MRI [(17.89±4.23) mm] ( t = -4.047, P < 0.001). The TT-RA [(24.28±4.27) mm], TD [2.95 (2.36, 4.08) mm], LTI (15.4°±3.85°), and TFA [0.42 (0.38, 0.49)] measured on CT were all significantly greater than those on MRI [(21.34±3.99) mm, 2.52 (1.64, 2.98) mm, 14.11°±3.58°, 0.38 (0.34, 0.44)] ( P < 0.001). The SA measured on CT (151.30°±6.74°) was significantly less than that measured on MRI (159.06°±5.40°) ( P < 0.001). The intra-observer ICC values for all indicators were greater than 0.9, and the inter-observer ICC values greater than 0.85. Conclusions:There are differences between CT and MRI in each indicator in evaluation of acute patellar dislocation in adolescents. The PT-TG measured on MRI and the TT-RA measured on CT can better evaluate the tibial tubercle lateralization; the indicators for trochlear dysplasia measured on MRI respond better to the severity of trochlea dysplasia than those on CT.

BACKGROUND:Neuropilin 1 plays a critical role in fracture healing,especially in osteogenesis-angiogenesis coupling. Osteogenesis-coupled angiogenesis is vital for fracture healing,including angiogenesis and bone formation (especially H-type vessel formation) and their association. OBJECTIVE:To review the research progress of neuropilin 1 in promoting osteogenesis-coupled angiogenesis during fracture healing.METHODS:The literature search was performed in the PubMed and Chinese National Knowledge Infrastructure databases for articles published from January 1982 to April 2024 using the search terms "Neuropilin-1,neuropilin 1,NRP1,neuropilin-1,NRP-1,Neuropilin 1,Nrp1,Nrp-1." We identified 43 articles associated with fracture healing,H-type vessels,arteries,bone cells,and angiogenesis-osteogenesis coupling. Moreover,24 articles were searched manually. Finally,67 papers were included.RESULTS AND CONCLUSION:(1) Angiogenesis,osteoblastogenesis,and their association were critical for angiogenesis-osteogenesis coupling during fracture healing. Especially H-type vessel formation was critical during fracture healing. H-type vessels consisted of endothelial cells and pericytes. Osteoblasts,osteoclasts,chondrocytes,and other skeletal cells were critical contributors to new bone formation. (2) Neuropilin 1 enhanced endothelial cell migration and stabilization,increased stability of endothelial cells and pericytes,and strengthened the link of endothelial cells and pericytes to initiate angiogenesis by vascular endothelial growth factor and platelet-derived growth factor. (3) Neuropilin 1 promoted bone regeneration by suppressing osteoclastogenesis and enhancing osteoclasts and chondrocyte formation. (4) Neuropilin 1 was a key factor in angiogenesis-osteogenesis coupling. (5) Topical application of neuropilin 1 and relative biologics,and combination neuropilin 1,nano drug-loading systems,and polymerized smart materials provided a new idea for treatment of fractures and hold great promise for extensive applications.

Objective To elucidate the effects and mechanisms of Biejiajian pill(BJJP)-containing serum on the malignant biological behaviors of hepatocellular carcinoma Huh7 cells.Methods This research knocked down CKLF-like MARVEL transmembrane domain containing 6(CMTM6)expression using a CMTM6-specific small interfering RNA(siRNA).Healthy Sprague-Dawley rats were used to prepare normal rat serum and low-(0.55 g/kg),medium-(1.1 g/kg),and high-(2.2 g/kg)BJJP-containing.Huh7 cells were cultured with normal fetal bovine serum(BC),normal rat serum(NC),and low-,medium-,and high-dose BJJP serum(LBJJP,MBJJP,and HBJJP,respectively).BJJP-containing serum and si-CMTM6 were applied to Huh7 cancer cells,and the proliferation,migration,and invasion abilities were evaluated by CCK-8 and Transwell assays,respectively.Protein expression levels of proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)markers,and CMTM6 were detected by Western blot.Results CMTM6 knockdown significantly reduced the mRNA and protein expression level of CMTM6 in Huh7 cells(P＜0.05).There were no significant differences between the BC and NC groups in terms of cell proliferation,migration,invasion,expression levels of PCNA,EMT markers,and CMTM6(all P＞0.05).BJJP-containing serum markedly inhibited Huh7 cell proliferation,migration,and invasion(P＜0.05),downregulated PCNA,CMTM6,N-cadherin,and Vimentin expression,and upregulated E-cadherin compared with the NC group(all P＜0.05).CMTM6 knockdown suppressed malignant behaviors,with reduced PCNA,Vimentin,and N-cadherin and elevated E-cadherin expression(all P＜0.05).Conclusions BJJP-containing serum can significantly inhibit Huh7 cell growth,invasion,migration,and EMT progression,potentially mediated via CMTM6 suppression.

OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*