BACKGROUND:Programmed cell death protein 1 belongs to the immunoglobulin gene superfamily and can regulate the differentiation of osteoblasts and affect bone homeostasis.However,there are few studies on the regulatory role and mechanism of programmed cell death protein 1 in diabetic osteoporosis.OBJECTIVE:To investigate the regulatory role and mechanism of programmed cell death protein 1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose environment.METHODS:(1)Animal experiment:A total of 12 Sprageu-Dawley rats were randomized into a control group(n=6)and a model group(n=6).The control group was fed routinely,whereas the model group was injected intraperitoneally with streptozotocin to establish a model of type 1 diabetes mellitus,and the high-fat feed was fed for 8 weeks to establish a model of type 1 diabetic osteoporosis.After 8 weeks of feeding,the femurs of rats in the two groups were taken and subjected to hematoxylin-eosin staining and micro-CT assay.The mRNA expression of programmed cell death protein 1 and programmed death ligand 1 was detected.(2)Cell experiment:Passage 3 rat bone marrow mesenchymal stem cells were randomly divided into four groups:normal control group,high-glucose model group cultured in low glucose medium,programmed cell death protein 1-silenced group transfected with programmed cell death protein 1 siRNA,and programmed cell death protein 1-silenced null group transfected with siRNA-NC.After 48 hours of transfection,the normal control group was cultured in a new low-glucose medium,and the other three groups were cultured in a high-glucose medium for another 48 hours of culture followed by osteogenic induction.After 21 days of osteogenic induction,alizarin red staining,and qRT-PCR(programmed cell death protein 1 and RUNX2 mRNA expression)and western blot(β-catenin,GSK-3β,p-GSK-3β and Axin2 protein expression)were performed.RESULTS AND CONCLUSION:In the animal experiment,hematoxylin-eosin staining and micro-CT assay showed successful modeling of type 1 diabetic osteoporosis in the model group.qRT-PCR assay showed that the mRNA expression of programmed cell death protein 1 and programmed cell death ligand 1 was higher in the model group than the control group(P<0.05).In the cell experiment,the results of alizarin red staining showed that the ability of mineralized nodule formation was lower in the high-glucose model group and the programmed cell death protein 1-silenced null group than in the control group and the programmed cell death protein 1-silenced group.Compared with the normal control group,the programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were elevated in the high-glucose model group and the programmed cell death protein 1-silenced null group(P<0.05),and the RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were decreased(P<0.05).Compared with the high-glucose model group and the programmed cell death protein 1-silenced null group,programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were decreased in the programmed cell death protein 1-silenced group(P<0.05),and RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were elevated(P<0.05).To conclude,programmed cell death protein 1 silencing can activate the Wnt/β-catenin and improve the osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose conditions.

This study aims to screen the diagnostic biomarkers for fecal antigen of Echinococcus granulosus(E.granulosus)in dogs with high specificity and sensitivity.The sheep-derived EgPSC artificially infected dogs were collected,and the negative and positive fecal samples of dogs with E.granulosus were prepared by arecoline hydrobromide leakage method.Polyclonal antibody,negative fecal antigen-polyclonal antibody conjugates and positive fecal antigen-polyclonal antibody conju-gates were purified by ammonium sulfate precipitation and affinity chromatography,three groups of samples were detected by ELISA and Western blot,LC-MS/MS and bioinformatics analysis were performed on the three groups of samples.The positive fecal antigen-polyclonal antibody con-jugate was used as the treatment group,the polyclonal antibody and the negative fecal antigen-polyclonal antibody conjugates were used as the control groups to screen the unique peptides of the treatment group.ELISA and Western blot showed that only the positive fecal antigen-polyclonal antibody conjugates were positive.According to LC-MS/MS and bioinformatics analysis,11 unique peptides were screened out only in the treatment group.Among them,3 proteins were related to E.granulosus,namely dysferlin,integrator complex 9 and diagnostic antigen gp50,which were mem-brane-associated proteins,INT complex components and diagnostic antigens.This study has pre-liminarily screened out three candidate canine E.granulosus fecal antigen diagnostic markers,pro-viding a reference for further exploration of diagnostic standards for E.granulosus,screening of echinococcosis target genes,and vaccine development.

Objective:To verify the efficacy of VELscope autofluorescence examination technology in the early warning of potential oral malignant diseases.Methods:80 patients with suspected dysplasia were included and underwent oral examination,visually en-hanced lesion scope(VELscope)autofluorescence examination and histopathology examination respectively,the fluorescence imaging results were compared with the histopathological results.Results:Pathological reports showed 64 cases with mild or no dysplasia,9 cases with moderate or severe dysplasia,1 case with moderate dysplasia without malignant transformation and 6 cases with cancer.The results of VELscope showed that there were 73 positive cases and negative 7 cases of fluorescence deletion.The sensitivity and specificity of VELscope were 93.75％and 9.37％respectively,and the sensitivity could reach 100％in the cancerous tissue.Con-clusion:As a non-invasive examination method,VELscope is highly sensitive but lowly specific.

This study aims to screen the diagnostic biomarkers for fecal antigen of Echinococcus granulosus(E.granulosus)in dogs with high specificity and sensitivity.The sheep-derived EgPSC artificially infected dogs were collected,and the negative and positive fecal samples of dogs with E.granulosus were prepared by arecoline hydrobromide leakage method.Polyclonal antibody,negative fecal antigen-polyclonal antibody conjugates and positive fecal antigen-polyclonal antibody conju-gates were purified by ammonium sulfate precipitation and affinity chromatography,three groups of samples were detected by ELISA and Western blot,LC-MS/MS and bioinformatics analysis were performed on the three groups of samples.The positive fecal antigen-polyclonal antibody con-jugate was used as the treatment group,the polyclonal antibody and the negative fecal antigen-polyclonal antibody conjugates were used as the control groups to screen the unique peptides of the treatment group.ELISA and Western blot showed that only the positive fecal antigen-polyclonal antibody conjugates were positive.According to LC-MS/MS and bioinformatics analysis,11 unique peptides were screened out only in the treatment group.Among them,3 proteins were related to E.granulosus,namely dysferlin,integrator complex 9 and diagnostic antigen gp50,which were mem-brane-associated proteins,INT complex components and diagnostic antigens.This study has pre-liminarily screened out three candidate canine E.granulosus fecal antigen diagnostic markers,pro-viding a reference for further exploration of diagnostic standards for E.granulosus,screening of echinococcosis target genes,and vaccine development.

Objective:To verify the efficacy of VELscope autofluorescence examination technology in the early warning of potential oral malignant diseases.Methods:80 patients with suspected dysplasia were included and underwent oral examination,visually en-hanced lesion scope(VELscope)autofluorescence examination and histopathology examination respectively,the fluorescence imaging results were compared with the histopathological results.Results:Pathological reports showed 64 cases with mild or no dysplasia,9 cases with moderate or severe dysplasia,1 case with moderate dysplasia without malignant transformation and 6 cases with cancer.The results of VELscope showed that there were 73 positive cases and negative 7 cases of fluorescence deletion.The sensitivity and specificity of VELscope were 93.75％and 9.37％respectively,and the sensitivity could reach 100％in the cancerous tissue.Con-clusion:As a non-invasive examination method,VELscope is highly sensitive but lowly specific.

BACKGROUND:Programmed cell death protein 1 belongs to the immunoglobulin gene superfamily and can regulate the differentiation of osteoblasts and affect bone homeostasis.However,there are few studies on the regulatory role and mechanism of programmed cell death protein 1 in diabetic osteoporosis.OBJECTIVE:To investigate the regulatory role and mechanism of programmed cell death protein 1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose environment.METHODS:(1)Animal experiment:A total of 12 Sprageu-Dawley rats were randomized into a control group(n=6)and a model group(n=6).The control group was fed routinely,whereas the model group was injected intraperitoneally with streptozotocin to establish a model of type 1 diabetes mellitus,and the high-fat feed was fed for 8 weeks to establish a model of type 1 diabetic osteoporosis.After 8 weeks of feeding,the femurs of rats in the two groups were taken and subjected to hematoxylin-eosin staining and micro-CT assay.The mRNA expression of programmed cell death protein 1 and programmed death ligand 1 was detected.(2)Cell experiment:Passage 3 rat bone marrow mesenchymal stem cells were randomly divided into four groups:normal control group,high-glucose model group cultured in low glucose medium,programmed cell death protein 1-silenced group transfected with programmed cell death protein 1 siRNA,and programmed cell death protein 1-silenced null group transfected with siRNA-NC.After 48 hours of transfection,the normal control group was cultured in a new low-glucose medium,and the other three groups were cultured in a high-glucose medium for another 48 hours of culture followed by osteogenic induction.After 21 days of osteogenic induction,alizarin red staining,and qRT-PCR(programmed cell death protein 1 and RUNX2 mRNA expression)and western blot(β-catenin,GSK-3β,p-GSK-3β and Axin2 protein expression)were performed.RESULTS AND CONCLUSION:In the animal experiment,hematoxylin-eosin staining and micro-CT assay showed successful modeling of type 1 diabetic osteoporosis in the model group.qRT-PCR assay showed that the mRNA expression of programmed cell death protein 1 and programmed cell death ligand 1 was higher in the model group than the control group(P<0.05).In the cell experiment,the results of alizarin red staining showed that the ability of mineralized nodule formation was lower in the high-glucose model group and the programmed cell death protein 1-silenced null group than in the control group and the programmed cell death protein 1-silenced group.Compared with the normal control group,the programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were elevated in the high-glucose model group and the programmed cell death protein 1-silenced null group(P<0.05),and the RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were decreased(P<0.05).Compared with the high-glucose model group and the programmed cell death protein 1-silenced null group,programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were decreased in the programmed cell death protein 1-silenced group(P<0.05),and RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were elevated(P<0.05).To conclude,programmed cell death protein 1 silencing can activate the Wnt/β-catenin and improve the osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose conditions.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

Body, qi, and spirit are the essential elements that constitute life. Based on the holistic view of life that integrates body, qi, and spirit, we aim to understand the pathogenesis of gastroesophageal reflux disease with emotional disorders. Our team believes that the fundamental characteristic of this disease is the coexistence of body, qi, and spirit disorders, manifested as physical tissue damage accompanied by functional decline, and the emergence of emotional disorders such as anxiety and depression. Among these, the body disorder is the intuitive sign, the qi disorder serves as the basis for the onset of the disease, and the spirit disorder represents the pathological essence of the comorbid emotional disorders. The treatment of this disease employs a holistic approach that addresses body, qi, and spirit simultaneously. Among these, adjusting the body is the first priority, with controlling acidity and protecting the mucous membrane as the crucial step. This helps control acid reflux and facilitates the repair of esophageal mucosal damage. Regulating qi is essential, with harmonizing the ascending and descending movements of qi at its core. This involves adjusting the qi movement of the internal organs and promoting the metabolism and transformation of essential substances. Nurturing the spirit is fundamental, with alleviating depression and nourishing the spirit as the focus. This improves emotional well-being and ensures that the spirit is nourished. Understanding the pathogenesis and treatment of gastroesophageal reflux disease with emotional disorders from the perspectives of body, qi, and spirit can provide new insights and strategies for clinical treatment of this disease.