Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Objective:We aimed to develop a nomogram in corporating multidetector computed tomography(MDCT)imaging features and clinicopathological indicators for the preoperative prediction of axillary lymph node metastasis(ALNM)in patients with triple-negative breast cancer(TNBC).Methods:We retrospectively analyzed data from 265 female patients with pathologically confirmed TNBC treated at Harbin Medical University Cancer Hospital between November 2020 and October 2024.Patients were randomly assigned into a training cohort(n=161)and a validation cohort(n=104)in a 6:4 ratio.Feature selection was performed using least absolute shrinkage and selection operator(LASSO)regression with 10-fold cross-validation.Independent predictors of ALNM were identified by multivariate Logistic regression analysis,and a nomogram was constructed accordingly.Model performance was assessed using receiver operating characteristic(ROC)curves,calib-ration plots,and decision curve analysis(DCA).Results:Three independent predictors of ALNM were identified:clinical N-stage(odds ratio[OR]=6.789;95%confidence interval[CI]:2.203-22.20;P=0.001),short-axis diameter of lymph nodes on CT(OR=1.686;95%CI:1.349-2.257;P<0.001),and cortical thickness(OR=6.296;95%CI:2.170-19.310;P=0.001).The nomogram showed strong discrimination,with areas under the ROC curve(AUC)of 0.918(95%CI:0.860-0.977)in the training cohort and 0.885(95%CI:0.809-0.962)in the validation cohort.Calibration was confirmed by Hosmer-Lemeshow tests(P=0.609 and P=0.694 for training and validation cohorts,respectively).DCA demon-strated clinical utility across probability thresholds of 0.02-0.96 and 0.03-0.87 in the training and validation cohorts,respectively.Conclu-sions:This nomogram,integrating MDCT imaging features and clinical indicators,provides a practical tool for individualized preoperative risk assessment and may aid clinical decision-making in patients with TNBC.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To investigate the influence of Salvia miltiorrhiza polyphenolate injection combined with tirofiban on the curative effect,macrophage migration inhibitory factor(MIF)level and hemorheology in patients with acute cerebral infarction(ACI).Methods A total of 116 patients with ACI were divided into the western medicine group(treated with tirofiban)and the combined group(treated with Salvia miltiorrhiza polyphenolate injection combined with tirofiban)by random number table method,with 58 cases in each group.Neurological deficit score(NIHSS)reduction was calculated,and the therapeutic effect was evaluated.Serum MIF,interleukin(IL)-6 and IL-1β levels were detected by enzyme-linked immunosorbent assay(ELISA)before and after treatment.Changes of hemorheological indexes(whole blood viscosity,whole blood low tangential viscosity and fibrinogen)of ACI patients were detected by SA-6600 automatic hemorheometer before and after treatment.The occurrence of adverse reactions during treatment was recorded.The modified Rankin Scale(mRS)was used to evaluate the clinical outcome at 90 days of onset,and the Barthel index was used to evaluate the living ability of the patients before and after treatment.Results The total clinical effective rate of ACI patients was higher in the combined group than that in the western medicine group(89.66%vs.74.14%,P＜0.05).After treatment,the levels of MIF,whole blood viscosity,whole blood low shear viscosity,fibrinogen,IL-6 and IL-1β were lower in 2 groups than those before treatment,and those were lower in the combined group than those in the western medicine group(P＜0.05).There was no significant difference in the total incidence of adverse reactions between the two groups(P＞0.05).The Barthel index was higher after treatment in the two groups,and which was higher in the combined group than that of the western medicine group(P＜0.05).The good outcome rate was higher in the combination group than that of the western medicine group(51.72%vs.32.76%,P＜0.05).Conclusion Salvia miltiorrhiza polyphenolate injection combined with tirofiban has a obvious effect for ACI patients,which can reduce serum levels of MIF and inflammatory factors,improve hemorheology indicators and has a high safety.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Objective:We aimed to develop a nomogram in corporating multidetector computed tomography(MDCT)imaging features and clinicopathological indicators for the preoperative prediction of axillary lymph node metastasis(ALNM)in patients with triple-negative breast cancer(TNBC).Methods:We retrospectively analyzed data from 265 female patients with pathologically confirmed TNBC treated at Harbin Medical University Cancer Hospital between November 2020 and October 2024.Patients were randomly assigned into a training cohort(n=161)and a validation cohort(n=104)in a 6:4 ratio.Feature selection was performed using least absolute shrinkage and selection operator(LASSO)regression with 10-fold cross-validation.Independent predictors of ALNM were identified by multivariate Logistic regression analysis,and a nomogram was constructed accordingly.Model performance was assessed using receiver operating characteristic(ROC)curves,calib-ration plots,and decision curve analysis(DCA).Results:Three independent predictors of ALNM were identified:clinical N-stage(odds ratio[OR]=6.789;95%confidence interval[CI]:2.203-22.20;P=0.001),short-axis diameter of lymph nodes on CT(OR=1.686;95%CI:1.349-2.257;P<0.001),and cortical thickness(OR=6.296;95%CI:2.170-19.310;P=0.001).The nomogram showed strong discrimination,with areas under the ROC curve(AUC)of 0.918(95%CI:0.860-0.977)in the training cohort and 0.885(95%CI:0.809-0.962)in the validation cohort.Calibration was confirmed by Hosmer-Lemeshow tests(P=0.609 and P=0.694 for training and validation cohorts,respectively).DCA demon-strated clinical utility across probability thresholds of 0.02-0.96 and 0.03-0.87 in the training and validation cohorts,respectively.Conclu-sions:This nomogram,integrating MDCT imaging features and clinical indicators,provides a practical tool for individualized preoperative risk assessment and may aid clinical decision-making in patients with TNBC.

A 38-year-old male patient with ulcerative colitis was treated with mesalazine enteric- coated tablets 2 g twice daily, and developed pruritus, dark urine and jaundice approximately 8 months later. Laboratory tests revealed severe liver function abnormalities, showing alanine aminotransferase (ALT) 1 251 U/L, aspartate aminotransferase (AST) 1 102 U/L, γ-glutamyl transferase (GGT) 615 U/L, alkaline phosphatase (ALP) 715 U/L, total bile acid (TBA) 244.72 μmol/L, total bilirubin (TBil) 456.9 μmol/L, direct bilirubin (DBil) 350.6 μmol/L and indirect bilirubin (IBil) 106.3 μmol/L. Abdominal CT showed no significant abnormalities. Mesalazine was discontinued, and hepatoprotective therapy was initiated with magnesium isoglycyrrhizinate, ademetionine 1,4-butanedisulfonate, acetylcysteine, and ursodeoxycholic acid. Viral hepatitis, Wilson′s disease, and hemochromatosis were ruled out in further investigations and liver biopsy. Severe drug-induced liver injury (DILI) caused by mesalazine was suspected, but autoimmune hepatitis (AIH) could not be entirely excluded. The hepatoprotective treatments were continued, and the patient′s liver function was improved significantly, showing ALT 48 U/L, AST 35 U/L, GGT 144 U/L, ALP 202 U/L, TBA 24.72 μmol/L, TBil 71.8 μmol/L, DBil 62.3 μmol/L and IBil 9.5 μmol/L by day 24 of treatments. Later, he was treated only with ursodeoxycholic acid and bicyclol. The patient′s liver function normalized approximately one and a half months later. However, the patient self-reinitiated mesalazine several days thereafter, and the liver function tests showed ALT 155 U/L and AST 80 U/L after about 2 months of resumed use. Mesalazine was discontinued again, and his liver function returned to normal within 1 week with supportive treatments. AIH was excluded, DILI induced by mesalazine was considered at last.

A 38-year-old male patient with ulcerative colitis was treated with mesalazine enteric- coated tablets 2 g twice daily, and developed pruritus, dark urine and jaundice approximately 8 months later. Laboratory tests revealed severe liver function abnormalities, showing alanine aminotransferase (ALT) 1 251 U/L, aspartate aminotransferase (AST) 1 102 U/L, γ-glutamyl transferase (GGT) 615 U/L, alkaline phosphatase (ALP) 715 U/L, total bile acid (TBA) 244.72 μmol/L, total bilirubin (TBil) 456.9 μmol/L, direct bilirubin (DBil) 350.6 μmol/L and indirect bilirubin (IBil) 106.3 μmol/L. Abdominal CT showed no significant abnormalities. Mesalazine was discontinued, and hepatoprotective therapy was initiated with magnesium isoglycyrrhizinate, ademetionine 1,4-butanedisulfonate, acetylcysteine, and ursodeoxycholic acid. Viral hepatitis, Wilson′s disease, and hemochromatosis were ruled out in further investigations and liver biopsy. Severe drug-induced liver injury (DILI) caused by mesalazine was suspected, but autoimmune hepatitis (AIH) could not be entirely excluded. The hepatoprotective treatments were continued, and the patient′s liver function was improved significantly, showing ALT 48 U/L, AST 35 U/L, GGT 144 U/L, ALP 202 U/L, TBA 24.72 μmol/L, TBil 71.8 μmol/L, DBil 62.3 μmol/L and IBil 9.5 μmol/L by day 24 of treatments. Later, he was treated only with ursodeoxycholic acid and bicyclol. The patient′s liver function normalized approximately one and a half months later. However, the patient self-reinitiated mesalazine several days thereafter, and the liver function tests showed ALT 155 U/L and AST 80 U/L after about 2 months of resumed use. Mesalazine was discontinued again, and his liver function returned to normal within 1 week with supportive treatments. AIH was excluded, DILI induced by mesalazine was considered at last.