BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective:To comprehensively evaluate the clinical effectiveness with respect to a single dose of tranexamic acid (TXA) given preoperatively for blood loss control in perioperative patients accepted craniomaxillofacial plastic and cosmetic surgery.Methods:Embase, PubMed, WanFang Data, VIP, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect randomized controlled trials (RCTs) related to appraise the efficacy in perioperative craniomaxillofacial plastic and cosmetic surgery patients used TXA from inception to August 2024. Based on the result of methodological heterogeneity, corresponding paired meta-analyses were carried out with a random-effects or fixed-effects model applying R 4.0.4 software. Subgroup analysis was performed based on type of surgery, patient age, regional distribution of patients, and sample size included in the studies. A meta-regression analysis was performed on studies that reported the effect of different doses of TXA on reducing perioperative bleeding. Sensitivity analysis was performed to verify the stability of the meta result. Egger’s test was used to analyze potential publication bias.Results:A total of 31 RCTs were included, involving 2 072 patients, with 1 051 in the TXA group and 1 021 in the placebo group. The paired meta-analysis random-effects model ( I2=90%) showed that compared with the control group, the use of TXA significantly reduced the amount of bleeding in perioperative patients[standardized mean difference ( SMD)=-1.13, 95% CI -1.47 to -0.80, P < 0.01]. Subgroup analysis revealed that TXA had a significant effect on reducing intraoperative bleeding in patients with different surgeries, ages, regions, and sample sizes. The most effective subgroups were cases in orthognathic surgery ( SMD=-1.44, 95% CI -2.07 to -0.80, P< 0.01), less than 30 year-old( SMD=-1.32, 95% CI -1.68 to -0.96, P< 0.01], Asian patients( SMD=-1.29, 95% CI -1.72 to -0.86, P< 0.01), less than 30 individuals ( SMD=-1.16, 95% CI -1.50 to -0.82, P< 0.01). The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) ( P>0.05). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger’s test indicated a certain degree of publication bias ( P < 0.01). Conclusion:Taken as a whole, existing evidence suggests that TXA can effectively reduce perioperative bleeding in patients undergoing craniofacial plastic surgery, regardless of its dosage administered. However, further clinical researches are still needed to provide more baselined data, transfusion-related indicators, and information on adverse events such as vascular embolism, in order to comprehensively evaluate and analyze the efficacy and safety of a single dose of TXA for perioperative blood loss control in patients treated with craniomaxillofacial plastic and cosmetic surgery.

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

Objective To explore the challenges faced by online appointment nurses during nasogastric intubation and to provide a reference for improvement of the quality and safety of the services provided by online appointment nursing.Methods A purposive sampling was employed to select 13 online appointment nurses from our hospital who had previously provided home nasogastric intubation services for patients.Semi-structured interviews were conducted with the online appointment nurses.The results acquired from the interviews were analysed using Colaizzi's method.Results Two themes were identified.Theme 1 covered the increased risks of nasogastric intubation due to the patients themselves and home environment,which included 4 sub-themes of difficulties in identification and response due to complex conditions of patient,high risk of a sudden asphyxia with poor resuscitation facility,psychological stress from unfamiliar home environment,and more challenges in risk identification due to limited conditions for performing home-based intubation procedures;Theme 2 covered the coping strategies of online-scheduled nurses,which included the improvement of knowledge and skills in emergency nursing to improve comfidence and judge ability of intubation,the strengthening of nurse-patient communication to build a trust and cooperation,the conduct of thorough assessment to ensure procedural safety,and the use of alternative tools and collaboration with family members.Conclusion Online appointment nurses face challenges and risks from both of the procedures and patients themselves during home based nasogastric intubation.Hospitals and relevant management should actively implement corresponding strategies,provide training and guidance for online appointment nurses,develop relevant regulations,and improve the management mechanisms of the internet platform to ensure the safety of home based nasogastric intubation for online appointment nurses and improve the quality of the"Internet Plus Nursing Services."

BACKGROUND:Leonurine has many biological activities such as improving microcirculation,anti-oxidation,anti-apoptosis,scavenging free radicals,anti-inflammation,and anti-fibrosis,and can promote osteogenic differentiation of bone marrow mesenchymal stem cells,which has the potential to be applied in the treatment of periodontitis. OBJECTIVE:To explore the anti-inflammatory and osteogenic effects of leonurine loading into chitosan/sodium glycerophosphate/sodium alginate hydrogel. METHODS:(1)Chitosan/sodium glycerophosphate/sodium alginate hydrogel(blank hydrogel)and chitosan/sodium glycerophosphate/sodium alginate/leonurus alkali hydrogel were prepared respectively.RAW 264.7 and MC3T3-E1 cells were inoculated with the two kinds of hydrogel.The cytotoxicity of hydrogels was detected by CCK-8 assay and live/dead cell staining.(2)RAW 264.7 cells were cultured in five groups.The blank group was cultured for 24 hours routinely.The lipopolysaccharide group was treated with lipopolysaccharide.The simple hydrogel group was treated with lipopolysaccharide and blank hydrogel.The drug-loaded hydrogel group was treated with lipopolysaccharide and drug-loaded hydrogel.The inhibitor group was treated with lippolysaccharide,drug-loaded hydrogel,and PI3K inhibitor LY294002.24 hours later,mRNA expression of inflammation-related factors was detected by qRT-PCR.Western blot assay was utilized to detect the protein expression of inflammation-related factors and PI3K/AKT signaling pathway.(3)MC3T3-E1 cells were inoculated in four groups.The blank group was cultured without any material.The simple hydrogel group was treated with blank hydrogel.The drug-loaded hydrogel group was treated with drug-loaded hydrogel.The inhibitor group was treated with drug-loaded hydrogel and PI3K inhibitor LY294002 for 7 days.Alkaline phosphatase staining was performed.mRNA expression levels of osteogenic factors were detected by qRT-PCR.The protein expression levels of the PI3K/AKT signaling pathway were detected by western blot assay. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead cell staining showed that the two kinds of hydrogels had no cytotoxic effect and had good cytocompatibility.(2)Compared with the blank group,the mRNA and protein expression levels of interleukin 6,tumor necrosis factor α,and interleukin 1β were significantly increased(P<0.05),and the protein expression levels of p-AKT,p-PI3K,p-p65,and p-IκBα were significantly increased in the lipopolysaccharide group(P<0.05).Compared with lipopolysaccharide group,mRNA and protein expression levels of the above indexes were decreased in drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(3)The activity of alkaline phosphatase in drug-loaded hydrogel group was higher than that in the blank group,simple hydrogel group,and inhibitor group(P<0.05).Compared with blank group,the mRNA expression levels of alkaline phosphatase,Runx2,osteocalcin,and type I collagen were increased(P<0.05),and the protein expression levels of p-AKT and p-PI3K were increased in the simple hydrogel group(P<0.05).Compared with the simple hydrogel group,the mRNA and protein expression levels of the above indexes were increased in the drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(4)These findings conclude that chitosan/sodium glycerophosphate/sodium alginate/leonurine hydrogel has anti-inflammatory and osteogenic effects,which may be related to the regulation of PI3K/AKT signaling pathway.

Objective: To comprehensively evaluate the clinical efficacy of a single dose of tranexamic acid (TXA) in reducing perioperative blood loss in patients undergoing craniomaxillofacial plastic and cosmetic surgery through meta-regression analysis. Methods: Embase, PubMed, Wanfang Data, VIP database, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect clinical studies evaluating efficacy of perioperative TXA administration in patients undergoing craniomaxillofacial plastic and cosmetic surgery, from inception to August 2024. Quality assessment of randomized controlled trials (RCTs) was performed using Cochrane Collaboration's Risk of Bias Tool. Based on the results of methodological heterogeneity, corresponding meta-analyses were conducted using either random-effects or fixed-effects models in R programming software. Results: Thirty-one articles were included, involving 2 072 patients who underwent craniomaxillofacial plastic and cosmetic surgeries. Among these patients, 1 051 were in the TXA treatment group, and 1 021 were in the control group. The paired meta-analysis showed that compared with the control group, the use of TXA significantly reduced bleeding volume in perioperative patients [standardized mean difference (SMD)=-1.13; 95%CI (-1.47, -0.80), P<0.001]. Subgroup analysis revealed that TXA significantly reduced intraoperative bleeding volume in patients across different surgeries, with the order of efficacy as follows: orthognathic surgery [SMD=-1.44; 95%CI (-2.07, -0.80), P<0.001], cleft palate repair [SMD=-1.32; 95%CI (-2.14, -0.50), P<0.001], rhinoplasty [SMD=-0.97; 95%CI (-1.63, -0.30), P<0.001], and craniosynostosis [SMD=-0.96; 95%CI (-1.40, -0.53), P=0.040]. The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) (P=0.650). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger's test indicated a certain degree of publication bias (Z=-3.40, P<0.001). Conclusion: Existing evidence suggests that TXA effectively reduces perioperative blood loss in patients undergoing craniofacial plastic surgery, regardless of its dosage administered.

The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

Codon optimization was performed for the M and HN genes of bovine parainfluenza virus type 3(BPIV3),and the recombinant shuttle plasmid Dual-M+HN was constructed.BPIV3 VLPs was prepared using the baculovirus expression system,and verified by Western blot,IFA and elec-tron microscopy.The successfully verified virus-like particle(VLPs)were mixed with MF59 adjuvant and CpG-ODN immunoenhancer to immunize mice by intramuscular-injection,and BPIV3 inactivated vaccine group and adjuvant control group were set up.The immune effect of BPIV3 VLPs was evaluated by monitoring mouse serum specific antibodies,neutralizing antibodies and hemagglutination inhibition antibodies.The results showed that the optimized codon adaptation in-dex(CAI)of the M and HN protein genes were 0.96 and 0.95,respectively,and the CG content reached 54.1％and 53.1％,respectively.The constructed recombinant plasmid was transformed in-to DHI0Bac for blue and white spot screening.The validated recombinant rod particles were trans-fected into Sf9 cells to obtain the rod-shaped virus pFastBac-M+HN.Under electron microscopy,BPIV3 VLPs with a diameter of approximately 180 nm were observed.IFA and Western blot ex-periments confirmed the successful expression and biological activity of the target protein.Through protein optimization,it was found that the protein expression was highest at an infection dose of MOI=5.After mixing 50 μg VLPs with MF59 adjuvant and CpG-ODN,mice were immunized by intramuscular injection.The results showed that the antibodies in the VLPs immunized group be-gan to rise at 2 weeks of the first immunization and reached their peak at 21 days of the second im-munization,with an average IgG antibody titer of 1∶40 228;The average titer of neutralizing anti-bodies is 1∶298;The titer of hemagglutination inhibition antibody is 1∶549,reaching the level of inactivated vaccine(P≥0.05),indicating that the VLPs prepared in this experiment can induce hu-moral immune response in the body.In summary,this study successfully prepared VLPs capable of self-assembly expression of BPIV3 HN and M proteins,and induced humoral immune response in mice,providing research basis for subsequent BPIV3 VLPs vaccine research.