Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

Objective To evaluate the efficacy and safety of different surgical approaches for extracting high-positioned supernumerary teeth in the maxillary anterior midline region.Three surgical methods,the labial approach,the palatal approach,and a longitudinal incision beside the upper lip frenum were compared.Methods A total of 102 patients were recruited from the Department of Oral and Maxillofacial Surgery at the Affiliated Stomatological Hospital of Anhui Medical University between January and September 2024.They were randomly assigned via a random-digit table to three groups:the labial approach group(n=32),the palatal approach group(n=34),and the longitudinal incision beside the upper lip frenum group(n=36).Operation time,bone removal volume,post-operative midfacial swelling,degree of pain,and patient satisfaction across the three groups were recorded and compared.Results The average operation time in the labial approach group((20.50±3.02)min)and the longitudinal incision group((21.66±2.31)min)were both significantly shorter than that in the palatal approach group((29.19±3.40)min).In contrast,the palatal approach group demonstrated markedly lower postoperative swelling and pain scores(P＜0.05),along with the highest patient satisfaction,as reflected in the OHIP-14 scale.However,the palatal approach required the greatest bone removal volume,measuring(91.19±9.86)mm3.Conclusion Despite the palatal approach yielding superior outcomes in terms of postoperative pain control,swelling reduction,and patient satisfaction,it necessitated longer operation time and involved greater bone removal.Meanwhile,the labial approach and the longitudinal incision beside the upper lip frenum were comparable in all measured parameters,showing no statistically significant differences.Therefore,when extracting high midline impacted teeth in the maxillary anterior region,the choice of surgical approach should balance safety,minimal invasiveness,and patient satisfaction.

AIM:To investigate the effect and mechanism of panax notoginseng saponins(PNS)inhibiting the proliferation of pulmonary artery smooth muscle cells(PASMCs)in rats under the ef-fect of monocrotaline(MCT).METHODS:PASMCs cultured in vitro were randomly divided into the normal control(Control)group,the monocrotaline(MCT)group,the panax notoginseng saponins(PNS)group,the knockdown(M+Si ADAM10)group,the knockdown postconditioning(M+P+Si ADAM10)group,the overexpression(M+OE AD-AM10)group,and the overexpression postcondi-tioning(M+P+OE ADAM10)group.After the model was constructed,the cell viability of each group was measured using the CCK-8 assay,along with Western blot utilized to detect the expression of proliferating cell nuclear antigen(PCNA),disinteg-rin metalloproteinase 10(ADAM10),and notch ho-mology protein-3(Notch3)at the cellular neurogen-ic locus,respectively.RESULTS:Under the effect of MCT,the viability of PASMCs was significantly en-hanced(P<0.05 or P<0.01);0-400 mg/L PNS was not toxic to the viability of normal cells,and 100 mg/L PNS could significantly inhibit the MCT-in-duced viability(P<0.01).After the knockdown of ADAM10,the viability of PASMCs significantly de-clined(P<0.01),and the expression of PCNA protein was significantly decreased(P<0.05),evidently in the M+P+Si ADAM10 group.Meanwhile,the ex-pression of ADAM10 and Notch3 protein was signif-icantly decreased(P<0.05 or P<0.01),evidently in the M+P+Si ADAM10 group.After overexpression of ADAM10,the viability of PASMCs was significant-ly enhanced(P<0.01),the expression of PCNA pro-tein was significantly increased(P<0.01),the PCNA value was slightly higher(P>0.05),and the expres-sion of ADAM10 and Notch3 protein was signifi-cantly elevated(P<0.05)in the M+P+OE ADAM10 group.Additionally,PASMCs overexpressing AD-AM10 with concomitant PNS exhibited a significant decrease in the expression of PCNA protein com-pared with PASMCs knocking down ADAM10(P<0.01),and the expression of ADAM10 and Notch3 protein declined to varying degrees(P>0.05).CON-CLUSION:Panax notoginseng saponins can mitigate MCT-induced PASMCs proliferation in rats by inhib-iting the ADAM10/Notch3 signaling pathway.

AIM:To investigate the effect and mechanism of panax notoginseng saponins(PNS)inhibiting the proliferation of pulmonary artery smooth muscle cells(PASMCs)in rats under the ef-fect of monocrotaline(MCT).METHODS:PASMCs cultured in vitro were randomly divided into the normal control(Control)group,the monocrotaline(MCT)group,the panax notoginseng saponins(PNS)group,the knockdown(M+Si ADAM10)group,the knockdown postconditioning(M+P+Si ADAM10)group,the overexpression(M+OE AD-AM10)group,and the overexpression postcondi-tioning(M+P+OE ADAM10)group.After the model was constructed,the cell viability of each group was measured using the CCK-8 assay,along with Western blot utilized to detect the expression of proliferating cell nuclear antigen(PCNA),disinteg-rin metalloproteinase 10(ADAM10),and notch ho-mology protein-3(Notch3)at the cellular neurogen-ic locus,respectively.RESULTS:Under the effect of MCT,the viability of PASMCs was significantly en-hanced(P<0.05 or P<0.01);0-400 mg/L PNS was not toxic to the viability of normal cells,and 100 mg/L PNS could significantly inhibit the MCT-in-duced viability(P<0.01).After the knockdown of ADAM10,the viability of PASMCs significantly de-clined(P<0.01),and the expression of PCNA protein was significantly decreased(P<0.05),evidently in the M+P+Si ADAM10 group.Meanwhile,the ex-pression of ADAM10 and Notch3 protein was signif-icantly decreased(P<0.05 or P<0.01),evidently in the M+P+Si ADAM10 group.After overexpression of ADAM10,the viability of PASMCs was significant-ly enhanced(P<0.01),the expression of PCNA pro-tein was significantly increased(P<0.01),the PCNA value was slightly higher(P>0.05),and the expres-sion of ADAM10 and Notch3 protein was signifi-cantly elevated(P<0.05)in the M+P+OE ADAM10 group.Additionally,PASMCs overexpressing AD-AM10 with concomitant PNS exhibited a significant decrease in the expression of PCNA protein com-pared with PASMCs knocking down ADAM10(P<0.01),and the expression of ADAM10 and Notch3 protein declined to varying degrees(P>0.05).CON-CLUSION:Panax notoginseng saponins can mitigate MCT-induced PASMCs proliferation in rats by inhib-iting the ADAM10/Notch3 signaling pathway.

Purpose To investigate the clinical significance of Gasdermin B(GSDMB)in ovarian cancer and its relationship with immune infiltration,aiming to explore novel biomarkers for immunotherapy.Methods Gene expres-sion matrix,somatic mutations,somatic copy number alterations(SCNA),and clinical data were obtained from the The Cancer Genome Atlas(TCGA)database.Copy number variation(CNV)analysis was performed using the GISTIC algorithm,and the CIBERSORT algorithm was applied to quantify the relative abundance of 22 immune cell types in the tumor microenvironment.Protein-protein interaction(PPI)network analysis was conducted to identify GSDMB-associ-ated interacting proteins.Additionally,multiplex immunofluorescence was used to verify the spatial distribution differ-ences of GSDMB protein in clinical ovarian cancer samples with different immune phenotypes and its interaction with immune cells.Results The expression level of the GSDMB gene was significantly higher in adjacent non-cancerous tissues than in tumor tissues(P＜0.001).Patients with high GSDMB expression exhibited elevated levels of immune chemokines(such as CXCL9 and CXCL10,P＜0.01)and tumor-killing lymphocytes(the proportion of CD8+T cell was significantly higher in the high-expression group than in the low-expression group,P＜0.001).CNV analysis re-vealed that GSDMB copy number alterations significantly influenced immune cell infiltration:patients with GSDMB cop-y number amplification had decreased infiltration levels of CD4+T cells and dendritic cells(P＜0.05),while those with deep deletion of GSDMB had significantly reduced infiltration levels of CD8+T cells and neutrophils(P＜0.01).PPI network analysis indicated that GSDMB might interact with key immune molecules,including IL-37,IL-18BP,IL-33,and IL-2(Pearson correlation coefficient r＞0.6,P＜0.001).Multiplex immunofluorescence analysis demonstra-ted that tumors with high GSDMB expression were more likely to exhibit an immune-inflamed phenotype(52.6％),while tumors in the low-expression group were predominantly immune-desert type(47.3％).Immunotherapy cohort a-nalysis suggested that GSDMB could serve as a potential predictive biomarker for immunotherapy responsiveness,with high predictive efficacy in multiple immune checkpoint inhibitor therapy cohorts targeting PD-1,PD-L1,and CTLA4(AUC＞0.8).Conclusion GSDMB plays a crucial role in reshaping the tumor microenvironment in ovarian cancer and may serve as a novel sensitizing target for immunotherapy.

Sampling is the first stage of the DNA Typing in forensic science,and some studies found that the sampling technology affected the outcomes of"Contact DNA"testing.Since swabs are the most commonly used collection instrument for"Contact DNA",the researchers in forensic science field should pay more attention to study the collection efficiency of swabs.However,currently the majority of relevant research is focused on downstream testing processes,such as typing and amplification;the corresponding work on sampling performance by swabs is quite limited.Furthermore,the absence of an internationally recognized standard procedure makes it impossible to directly compare the collection results among laboratories.In this paper,a review on the use of swabs in the forensic science field is presented.It analyzes the collection efficiency,advantages and disadvantages of different swabs,and investigates the need and feasibility of developing a standardized method to evaluate the swab collection efficiency,for improving the sampling performance of swabs and ultimately increasing the detection rate of"Contact DNA"in forensic science.

Diabetic macular edema(DME), a serious complication of diabetic retinopathy(DR), is a chronic condition caused by multiple factors. Throughout its progression, inflammatory factors and vascular endothelial growth factor(VEGF)play a critical role. Anti-VEGF drugs have shown significant effectiveness in the treatment of DME; however, some patients may experience persistent DME after injection or require frequent injections. Dexamethasone intravitreal implants(DEX implants)serve as a sustained-release implant characterized by a reasonable release profile and high bioavailability. They offer safe, effective, and prolonged anti-inflammatory effects, aiding in the repair of retinal barrier and reduction of exudation. To further enhance patients' visual quality, exploring the efficacy of DEX implants in combination with existing treatment regimens has great clinical significance. This review primarily discusses the research advancements in DEX implants, focusing on their pharmacological properties, indications for use, and their combination with existing drugs and treatment methods. It also evaluates the advantages and disadvantages of combination therapy or switching to DEX implants compared to current standard treatments, aiming to provide guidance for personalized treatment options for patients with DME.

Purpose To investigate the clinical significance of Gasdermin B(GSDMB)in ovarian cancer and its relationship with immune infiltration,aiming to explore novel biomarkers for immunotherapy.Methods Gene expres-sion matrix,somatic mutations,somatic copy number alterations(SCNA),and clinical data were obtained from the The Cancer Genome Atlas(TCGA)database.Copy number variation(CNV)analysis was performed using the GISTIC algorithm,and the CIBERSORT algorithm was applied to quantify the relative abundance of 22 immune cell types in the tumor microenvironment.Protein-protein interaction(PPI)network analysis was conducted to identify GSDMB-associ-ated interacting proteins.Additionally,multiplex immunofluorescence was used to verify the spatial distribution differ-ences of GSDMB protein in clinical ovarian cancer samples with different immune phenotypes and its interaction with immune cells.Results The expression level of the GSDMB gene was significantly higher in adjacent non-cancerous tissues than in tumor tissues(P＜0.001).Patients with high GSDMB expression exhibited elevated levels of immune chemokines(such as CXCL9 and CXCL10,P＜0.01)and tumor-killing lymphocytes(the proportion of CD8+T cell was significantly higher in the high-expression group than in the low-expression group,P＜0.001).CNV analysis re-vealed that GSDMB copy number alterations significantly influenced immune cell infiltration:patients with GSDMB cop-y number amplification had decreased infiltration levels of CD4+T cells and dendritic cells(P＜0.05),while those with deep deletion of GSDMB had significantly reduced infiltration levels of CD8+T cells and neutrophils(P＜0.01).PPI network analysis indicated that GSDMB might interact with key immune molecules,including IL-37,IL-18BP,IL-33,and IL-2(Pearson correlation coefficient r＞0.6,P＜0.001).Multiplex immunofluorescence analysis demonstra-ted that tumors with high GSDMB expression were more likely to exhibit an immune-inflamed phenotype(52.6％),while tumors in the low-expression group were predominantly immune-desert type(47.3％).Immunotherapy cohort a-nalysis suggested that GSDMB could serve as a potential predictive biomarker for immunotherapy responsiveness,with high predictive efficacy in multiple immune checkpoint inhibitor therapy cohorts targeting PD-1,PD-L1,and CTLA4(AUC＞0.8).Conclusion GSDMB plays a crucial role in reshaping the tumor microenvironment in ovarian cancer and may serve as a novel sensitizing target for immunotherapy.

Objective To prepare an advanced irrigation device equipped with a specialized nozzle designed to access the pericoronal blind sac of impacted wisdom teeth,and evaluate its efficacy in plaque removal.Methods 3D-printer was utilized to develop pericoronal models simulating mandibular wisdom teeth with high vertical impaction and varying soft tissue coverage(0%,25%,50%,and 75%,respectively)and personalized pericoronal irrigator.The obtained pericoronal models were randomly divided into 3 groups,treated with personalized precision pericoronal flushing,routine flushing and brushing,respectively,and,under a pressures of 45 psi or 75 psi(1 psi=6 894.76 Pa),were performed to clean the test surfaces of plaque-biofilm-obstructed wisdom teeth,respectively.Images of the tooth surfaces were analyzed before and after cleaning,and the cleaning rate was calculated using Python software.Results For wisdom teeth with 50%and 75%pericoronal soft tissue coverage,at a pressure of 45 psi,the precision pericoronal flushing group demonstrated significantly higher cleaning rate when compared to the brushing and routine flushing groups(P<0.05).At 0%and 25%pericoronal soft tissue coverage,the precision pericoronal flushing and brushing groups exhibited significantly higher cleaning rates than the routine flushing group(P<0.05).Furthermore,at 75 psi,the precision pericoronal flushing group achieved a significantly higher cleaning rate across all 4 levels of pericoronal soft tissue coverage than both the routine flushing and brushing groups(P<0.05).Notably,the precision pericoronal flushing group at 75 psi obtained significantly higher cleaning rate than at 45 psi across 0%,25%,and 50%pericoronal soft tissue coverage(P<0.05).Conclusion The precision pericoronal irrigation device demonstrates significantly superior cleaning efficacy for vertically impacted mandibular third molars compared to conventional irrigation devices and manual tooth brushing.It is an effective device for preventing and treating pericoronitis.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent