Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Quality control (QC) of biospecimens from oral and maxillofacial tumors patients constitutes a critical foundation for the prevention, diagnosis, treatment, and precision medicine research of these diseases. Biospecimen quality directly governs the discovery and validation of disease biomarkers, the elucidation of pathogenesis, and the efficacy of clinical translation. QC spans the entire biospecimen lifecycle—encompassing collection, processing, storage, transportation, and utilization. Its primary objectives are to ensure sample integrity, reliability, traceability, and consistency, thereby guaranteeing the robustness of research data; the accuracy of molecular subtyping, biomarker identification, and treatment response prediction; and the precision of clinical decision-making. However, current QC frameworks for these biospecimens remain underdeveloped. Drawing on domestic and international technical standards, regulatory guidelines, and recent research advances, this paper elaborates on the importance of implementing a QC management system throughout the biospecimen lifecycle. It focuses on QC methodologies tailored to diverse biospecimen types, examining how standardized sampling procedures, regulated preprocessing workflows, and optimized long-term storage conditions influence sample quality. We aim to provide concrete guidance and a transferable paradigm for establishing standardized QC protocols and an informatics-enabled traceability system specific to oral and maxillofacial tumors. Such efforts are intended to enhance the research value and clinical utility of these biospecimens, furnishing reliable sample resources and technical support for the development of precision diagnostics and therapeutics. Furthermore, we advocate for a dual-track “QC plus Ethics” management framework within biobanks. This approach would reinforce ethical and legal safeguards, establishing a robust barrier to support safe scientific innovation and clinical translation.

Objective: To evaluate the cost utility of different influenza vaccination strategies for primary and secondary school students in Anshun City, so as to provide healtheconomic evidence for influenza prevention and control in this population. Methods: Based on the demographic data of 380 700 students aged 5-14 in Anshun City in 2024, a decision tree model for different influenza vaccination strategies was constructed. The incremental cost utility ratio (ICUR) and net monetary benefit (NMB) were calculated, and sensitivity analysis was performed to assess the robustness of the model results. Results: For influenza vaccination among primary and secondary school students in Anshun City, compared with the selfpaid strategy (2% coverage), the free strategy (45% coverage) and the target strategy (70% coverage) both yielded an ICUR of -7 874.29 yuan per quality adjusted life year (QALY). When using 1 and 3 times the per capita Gross Domestic Product (GDP) as the willingness to pay thresholds, the per capita Net Monetary Benefit (NMB) was 1 000, 1 600 and 2 900, 4 500 RMB, respectively. The number of influenza infections or school absenteeism decreased by 25% and 40%, while saving a total cost of (46.779 5 and 73.976 8) million yuan, and increasing QALY by 5 940.79 and 9 394.73, respectively. Sensitivity analysis showed that within the reasonable fluctuation range of parameters, the ICUR remained consistently lower than the one and three times willingness to pay. Furthermore, 99% of the simulation results for both the free and target strategies fell below those thresholds, indicating high robustness of the model results. Conclusion Implementing free and target influenza vaccination strategies for primary and secondary school students in Anshun City offer distinct cost utility advantages, and the advantage enhances as the vaccination coverage rate increases.

Objective To investigate the role and mechanism of paeoniflorin(PF)in sepsis-associated acute kidney injury(SA-AKI)in mice.Methods Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS.Twenty-four male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were randomly divided into Control group,model group,PF group(intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group(10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration).The renal histopathological changes were observed by HE staining and Paller scoring.ELISA was used to determine the contents of serum creatinine(Scr),neutrophil gelatinase-associated lipocalin(NGAL)and lactate,and renal contents of hexokinase 2(HK2),lactate dehydrogenase A(LDHA),IL-1β and IL-18.Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.Results Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score(P＜0.05),increased serum Scr and NGAL levels(P＜0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18(P＜0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue(P＜0.05).PF treatment attenuated the renal tissue damage,decreased Paller score(P＜0.05),reduced serum Scr and NGAL levels(P＜0.05),HK2,LDHA and serum lactate levels,and contents of IL-1 β and IL-18 in renal tissues(P＜0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleusβ-catenin and c-Myc when compared with the levels in the model group(P＜0.05).While,addition of BML284 reversed above effects of PF treatment with significant differences(P＜0.05).Conclusion PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

In order to study the pathogenesis of meningitis in lambs caused by Enterococcus faecalis(E.faecalis),and to elucidate the pathogenesis of meningitis from the circRNA level,E.faecalis(named XJ6)was reintroduced into the host to construct a lamb brain tissue injury model,and then the lamb brain tissues were selected for whole genome transcript sequencing at four time in-tervals(24,48,60 and 72 h).Based on the transcriptomics sequencing results,the differential cir-cRNAs were preliminarily screened,and the accuracy of the transcriptomics data was verified by real-time fluorescence quantification.The results showed that the experiments successfully con-structed the brain tissue injury model of E.faecalis infected lambs,and the GO enrichment analy-sis results showed the most significant 10 cellular components,10 biological processes,and 10 mo-lecular functions.KEGG pathway enrichment results revealed that the genes targeted by differenti-al circRNAs were mainly focused on signaling pathways regulating the neuronal cells,the MAPK signaling pathway,the Rap1 signaling pathway,VDEF signaling pathway,Apelin signaling path-way,vascular smooth muscle contraction,and cancer development.The differentially expressed cir-cRNAs validated by real-time quantitative PCR were completely consistent with the transcriptomic results.Among them,novel_circ_0004872 was identified as a candidate circRNA potentially involved in altering the permeability of the blood-brain barrier in lambs,providing a theoretical ref-erence for exploring the regulatory role of circRNAs in blood-brain barrier function.

AIM:To investigate the effects and underlying mechanisms of paeoniflorin(PF)on lipopolysac-charide(LPS)-induced intestinal injury in septic mice,using a combination of network pharmacology,molecular docking,and animal experiments.METHODS:Network pharmacology was used to identify key active components and therapeutic targets of Red Peony for treating sepsis.Molecular docking was performed to explore the binding affinity be-tween PF and silent information regulator 1(SIRT1).An LPS-induced mouse model of sepsis with intestinal injury was es-tablished.Samples were collected 24 h after modeling,and hematoxylin-eosin(HE)staining was performed to observe pathological changes in intestinal tissues.Chiu's scoring system was utilized to evaluate the extent of intestinal injury.En-zyme-linked immunosorbent assay(ELISA)was employed to measure levels of inflammatory factors in intestinal tissues,including interleukin-1β(IL-1β)and IL-18,as well as indicators of intestinal permeability such as diamine oxidase(DAO)and intestinal-type fatty acid-binding protein(I-FABP),alongside serum levels of D-lactate and the aerobic gly-colysis product L-lactate.Western blot analysis was performed to assess changes in protein levels of SIRT1,M2-type pyru-vate kinase(PKM2),and NOD-like receptor protein 3(NLRP3)in intestinal tissues.RESULTS:Network pharmacolo-gy suggested that paeoniflorin,an active component of Red Peony,treats sepsis by targeting SIRT1 among other proteins.Molecular docking revealed a strong binding affinity of PF with SIRT1.In vivo experimentation revealed significant patho-logical damage in intestinal tissues in the LPS group compared to the control group as evidenced by HE staining.Chiu's score,along with levels of IL-1β,IL-18,D-lactate,and L-lactate were significantly elevated,while DAO and I-FABP levels were reduced(P＜0.05).SIRT1 expression decreased,while PKM2 and NLRP3 levels increased(P＜0.05).In contrast,the LPS+PF group displayed reduced intestinal histopathological injury,lower Chiu's scores,and decreased levels of IL-1β,IL-18,D-lactate,and L-lactate,along with increased DAO and I-FABP levels(P＜0.05).Notably,SIRT1 protein expression increased while PKM2 and NLRP3 levels decreased(P＜0.05).Furthermore,compared to the LPS+PF group,the LPS+PF+EX527 group exhibited exacerbated intestinal histopathological injury,increased Chiu's scores,as well as elevated levels of IL-1β,IL-18,D-lactate,and L-lactate,alongside reduced DAO and I-FABP levels(P＜0.05),decreased SIRT1 expression,and increased PKM2 and NLRP3 levels(P＜0.05).CONCLUSION:Paeoni-florin effectively alleviates intestinal injury in mice with sepsis,potentially through the upregulation of SIRT1 expression and the inhibition of PKM2-mediated aerobic glycolysis,which subsequently reduces the activation of NLRP3 inflamma-somes,mitigates the release of inflammatory factors,and lessens intestinal inflammation.

Objective To explore the clinical significance of pulse pressure variability(PPV)in early prevention and diagnosis of prostate resection syndrome by observing the changes in PPV during transurethral resection of the prostate.Methods Eighty patients undergoing transurethral resection of the prostate(TURP)under general anesthesia from March to April 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.The control group underwent routine monitoring of invasive blood pressure,while the observation group continued to monitor PPV in addition to invasive blood pressure monitoring.Observe and record the hemodynamic parameters,electrolyte Na+,K+,CL-,Changes in hemoglobin(Hb)and hematocrit(Hct),recording surgical time,intraoperative lavage fluid dosage,and occurrence of dilutive hyponatremia(TURS).Results One patient in the observation group experienced two unexplained drops in blood pressure and heart rate during surgery,and was diagnosed with TURS based on blood gas analysis.Among them,the observation group showed a decreasing trend in PPV with the prolongation of surgery time.PPV gradually decreased at 45～60 minutes after surgery,and at 90 minutes after surgery,PPV decreased significantly compared to preoperative levels.Among them,6 patients had a 50%decrease in PPV compared to preoperative levels.For patients with significantly reduced PPV,immediate treatment was given 10～20 mg of furosemide and 10 mg of dexamethasone.By the end of surgery,PPV had basically recovered to preoperative levels.Both groups of patients showed varying degrees of decrease in Na+,K+,Hct,and Hb levels.Conclusions PPV can reflect the volume status of patients.When PPV decreases by more than 50%compared to preoperative levels and there are unexplained hemodynamic changes and abnormal clinical manifestations during surgery,it is necessary to be vigilant and handle them promptly to reduce and prevent the occurrence of TURS.

Objective To investigate the effects and mechanisms of supplemented Buyang Huanwu decoction(BYHWD)on zinc home-ostasis and reproductive function in oligoasthenozoospermia(OAS)rats.Methods As many as 60 male SD rats were randomly divided into control,OAS,L-carnitine(0.323 g/kg),BYHWD low-dose(BYHWD-L,19.5 g/kg),BYHWD medium-dose(BYHWD-M,39 g/kg),and BYHWD high-dose(BYHWD-H,78 g/kg)groups,with 10 rats in each group.Except for the control group,all other groups were admini-stered adenine by gavage to establish an OAS model.After successful construction of the model,each group was treated by gavage with the corresponding drug doses or physiological saline once daily for 4 weeks.The general condition of the rats was recorded,testicular and epididymal coefficients were calculated,and sperm water volume and vitality were measured.Enzyme linked immunosorbent assay(ELISA)was used to measure the levels of serum testosterone(T),estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),as well as the levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor α(TNF-α)and zinc containing enzymes alcohol dehydrogenase(ADH),alkaline phosphatase(ALP),and lactate dehydrogenase(LDH)in testicular tissue.The zinc con-tent in testicular tissue were also measured.Pathological changes in testicular tissue were observed using hematoxylin eosin(HE)staining.Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor kappa-B(NF-κB)protein expression in testicu-lar tissue were identified using immunohistochemistry.Results Compared to the control group,the OAS group exhibited significantly lower testicular and epididymal coefficients,sperm motility,sperm count,serum T and E2 levels(P＜0.05)and significantly higher FSH,LH,and PRL levels(P＜0.05).Furthermore,the OAS group showed significantly lower testicular tissue zinc content and levels of zinc containing enzymes ADH,ALP,and LDH(P＜0.05)than the control group.Conversely,IL-1β,IL-6,and TNF-α levels,along with protein expressions of TLR4,MyD88,and NF-κB were significantly higher in the OAS group than in the control group(P＜0.05).Compared to the OAS group,each drug intervention group showed improvements in testicular and epididymal coefficients,sperm motility,sperm count,T and E2 levels,testicular zinc content and zinc containing enzymes(ADH,ALP,and LDH)levels.Furthermore,the intervention groups demonstrated reduced FSH,LH,PRL,IL-1β,IL-6,and TNF-α levels,and TLR4/MyD88/NF-κB signaling pathway protein expression(P＜0.05).Conclusion BYHWD improves the reproductive function of OAS rats,potentially by regulating zinc homeostasis and TLR4/MyD88/NF-κB signaling pathway,consequently reducing the inflammatory response.

Aberrant expression of Colgalt1 is closely associated with tumorigenesis and tumor progres-sion;however,the mechanism by which it regulates macrophages to influence tumor development remains poorly understood.This study aimed to establish a macrophage-specific Colgalt1 gene knockout mouse model to delve into the mechanisms through which Colgalt1 modulates macrophage function and subse-quently affects the occurrence and progression of tumor-related diseases.Initially,Colgalt1flox+mice were generated using gene editing techniques,followed by crossing with Lyz2-Cre+mice,which exhibit tissue-specific expression in the myeloid lineage(including monocytes and mature macrophages).Through this strategy,mice with the genotype Colgalt1-/-Lyz2-Cre+were successfully obtained,achieving conditional knockout of the Colgalt1 gene in macrophages.Colgalt1flox/flox Lyz2-Cre-mice were used as control.PCR and agarose gel electrophoresis were employed to identify the Flox and Cre genotypes of the knockout mice.RT-qPCR and Western Blot techniques were utilized to detect the expression levels of Colgalt1 in BMDMs from knockout mice at both the mRNA and protein levels,respectively.Western Blot results re-vealed a significant downregulation of Colgaltl expression in BMDMs from knockout mice compared to controls(P＜0.01).RT-qPCR results demonstrated a significant reduction in Colgalt1 mRNA levels in BMDMs from knockout mice compared to contro1s(P＜0.001),while no significant differences in Col-galt1 mRNA expression were observed in liver,lung,or spleen tissues between the two groups.Addition-ally,immunohistochemistry was employed to detect Colgalt1 expression in liver-specific macrophages,re-vealing an absence of Colgalt l-positive staining in liver macrophages from knockout mice.HE staining was used to observe cellular morphology in liver tissues from both groups of mice,showing no significant differences in cellular morphology or obvious pathological changes in tissues and organs.Moreover,the o-verall survival of the mice was not affected.Finally,RT-qPCR was used to assess the expression of mac-rophage-related inflammatory factors in BMDMs from both groups of mice.The results indicated that com-pared to controls,knockout mice exhibited downregulated expression of TNF-α(P＜0.05)and signifi-cantly upregulated expression of IL-10(P＜0.01),Arginase1(P＜0.001),and CD206(P＜0.001)in BMDMs,suggesting an anti-inflammatory trend and M2 polarization of macrophages following Colgalt 1 knockout.In summary,this study successfully established a macrophage-specific Colgalt1 gene knockout mouse model,providing a more reliable experimental animal model for in-depth exploration of the specific roles of Colgalt1 in macrophage functional regulation and the pathogenesis of tumor-related diseases.This model holds promise for identifying novel therapeutic targets and strategies for tumors and other diseases.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*