ObjectiveTo investigate the mechanism of Xiaozhi Qinggan decoction （XQD） in preventing and treating metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating ferroptosis， network pharmacology， in vitro and in vivo experiments. MethodsIn the in vivo experiment， mouse MASLD models were established by high-fat diet （HFD） induction. The model mice were randomly assigned to a positive control group （silybin， 50 mg·kg^-1）， low-， medium- and high-dose XQD groups （4.725， 9.45， 18.9 g·kg^-1）， with a normal control group. After 4 weeks of modeling， mice except the normal group were administered intragastrically for 8 consecutive weeks. Liver function， serum lipid levels， hepatic histopathology， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reduced glutathione （GSH） and oxidized glutathione （GSSG） and Fe²⁺ were detected. The mRNA and protein expression of p53， SLC7A11 and GPX4 were determined by quantitative Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. In the network pharmacology analysis， active components and potential targets of XQD for MASLD were screened， followed by functional and pathway enrichment analyses， and molecular docking was performed to verify the target binding activity. In the in vitro experiment， the optimal concentration of XQD-containing serum was screened by cytotoxicity assay. HepG2 cells were transfected with ov-NC or ov-p53 plasmid， and a lipid accumulation model was induced by free fatty acid （FFA， 1.0 mmol·L^-1）. Cells were divided into a normal group， FFA model group， ov-NC+XQD （15%） group and ov-p53+XQD （15%） group. Intracellular Fe²⁺ level and lipid accumulation were evaluated， and the protein expression of p53， SLC7A11 and GPX4 was measured by Western blot. ResultsCompared with the normal group， the model group exhibited markedly elevated body weight， liver weight， liver index， fasting blood glucose， AUC of glucose tolerance test， serum liver function and blood lipid levels at week 12 （P<0.01）. Hepatic steatosis and inflammatory infiltration were observed by pathological staining. Additionally， hepatic levels of MDA， SOD and Fe²⁺ were increased （P<0.01）， while GSH， GSSG and the GSH/GSSG ratio were decreased （P<0.01）. The mRNA and protein expression of hepatic p53 was upregulated （P<0.01）， whereas the expression of SLC7A11 and GPX4 was downregulated （P<0.01）. Compared with the model group， the low- and medium-dose XQD groups showed significantly decreased body weight at week 12 （P<0.05）. The silybin group， together with the medium- and high-dose XQD groups， presented reduced liver weight and liver index （P<0.05）. Fasting blood glucose and the AUC of glucose tolerance test were lowered in all four treatment groups （P<0.05， P<0.01）. Pathological staining revealed alleviated hepatic steatosis and inflammation， accompanied by decreased serum liver function and blood lipid levels （P<0.05， P<0.01）. Moreover， hepatic MDA and SOD levels were markedly reduced， while GSH， GSSG and the GSH/GSSG ratio were significantly elevated （P<0.05， P<0.01）. Hepatic Fe²⁺ level was decreased （P<0.01）. The mRNA and protein expression of hepatic p53 was downregulated， and the expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. Network pharmacology analysis identified quercetin， kaempferol， luteolin， tanshinone IIA and isorhamnetin as the core active components of XQD， with p53 serving as the key target. Stable binding was verified between these active components and the p53 protein. The optimal concentration of XQD-containing serum in vitro was determined to be 15%. Compared with the normal group， the model group showed increased intracellular Fe²⁺ and lipid accumulation， significantly upregulated p53 protein expression （P<0.01）， and markedly downregulated SLC7A11 and GPX4 protein expression （P<0.01）. Compared with the model group， the ov-NC group exhibited reduced Fe²⁺ and lipid accumulation， downregulated p53 expression， and upregulated SLC7A11 and GPX4 expression. In the ov-p53 group， p53 expression was upregulated （P<0.01）， while SLC7A11 and GPX4 expression was downregulated （P<0.01）. ConclusionXQD inhibits ferroptosis by downregulating p53 and upregulating SLC7A11 and GPX4， thereby alleviating oxidative stress and lipid peroxidation in hepatocytes and improving MASLD.

OBJECTIVES: The presence of multi-scale skin lesion regions and image noise interference and limited resources of auxiliary diagnostic equipment affect the accuracy of skin disease detection in skin disease detection tasks. To solve these problems, we propose a highly efficient and lightweight skin disease detection model using an improved RT-DETR model. METHODS: A lightweight FasterNet was introduced as the backbone network and the FasterNetBlock module was parametrically refined. A Convolutional and Attention Fusion Module (CAFM) was used to replace the multi-head self-attention mechanism in the neck network to enhance the ability of the AIFI-CAFM module for capturing global dependencies and local detail information. The DRB-HSFPN feature pyramid network was designed to replace the Cross-Scale Feature Fusion Module (CCFM) to allow the integration of contextual information across different scales to improve the semantic feature expression capacity of the neck network. Finally, combining the advantages of Inner-IoU and EIoU, the Inner-EIoU was used to replace the original loss function GIOU to further enhance the model's inference accuracy and convergence speed. RESULTS: The experimental results on the HAM10000 dataset showed that the improved RT-DETR model, as compared with the original model, had increased mAP@50 and mAP@50:95 by 4.5% and 2.8%, respectively, with a detection speed of 59.1 frames per second (FPS). The improved model had a parameter count of 10.9 M and a computational load of 19.3 GFLOPs, which were reduced by 46.0% and 67.2% compared to those of the original model, validating the effectiveness of the improved model. CONCLUSIONS The proposed SD-DETR model significantly improves the performance of skin disease detection tasks by effectively extracting and integrating multi-scale features while reducing both parameter count and computational load.
Humans ; Skin Diseases/diagnosis* ; Skin/pathology* ; Neural Networks, Computer ; Algorithms

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

Objective:To compare the clinical effects of using xenogenic bone graft materials with or without collagen components for tooth micro crestal flap-alveolar ridge preservation (MCF-ARP) at molars with severe periodontitis.Methods:This study included patients who visited Department of Periodontology, Peking University School and Hospital of Stomatology from May to November 2023 due to severe periodontitis, requiring tooth extraction and planning for implant-retained prostheses. A total of 24 molars from 24 patients with severe periodontitis were assigned into two groups: the deproteinized bovine bone mineral (DBBM) group and the DBBM with collagen (DBBM-C) group. Twelve affected teeth from 12 patients were included in each group. Both groups underwent minimally invasive tooth extraction and MCF-ARP, with DBBM and DBBM-C implanted in the extraction socket, respectively. Cone beam CT (CBCT) was performed before and 6 months after the surgery for assessing changes of hard tissue. Intraoral scanning was performed before and at 2 weeks, 1 month, 3 months, and 6 months after the surgery for assessing soft tissue contour changes and patterns in both groups.Results:After 6 months of healing, the central bone height increased by (8.35±2.25) mm in the DBBM group and (7.70±2.36) mm in the DBBM-C group. The ridge width at 1 mm apically from the higher bone crest increased by 6.43 (-0.76,7.96) mm in the DBBM group and 6.01 (5.41,7.90) mm in the DBBM-C group. There was no statistically significant difference in the changes of bone height and width between the two groups (all P>0.05). In terms of soft tissue contour changes, although the buccal contour collapses were less in the DBBM-C group, the two groups showed no statistically significant difference (all P>0.05). Conclusions:Within the limitations of this study, it was demonstrated that the clinical effects of MCF-ARP using xenogenic bone graft materials with or without collagen components in molars with severe periodontitis were comparable.

Objective:To compare the clinical effects of using xenogenic bone graft materials with or without collagen components for tooth micro crestal flap-alveolar ridge preservation (MCF-ARP) at molars with severe periodontitis.Methods:This study included patients who visited Department of Periodontology, Peking University School and Hospital of Stomatology from May to November 2023 due to severe periodontitis, requiring tooth extraction and planning for implant-retained prostheses. A total of 24 molars from 24 patients with severe periodontitis were assigned into two groups: the deproteinized bovine bone mineral (DBBM) group and the DBBM with collagen (DBBM-C) group. Twelve affected teeth from 12 patients were included in each group. Both groups underwent minimally invasive tooth extraction and MCF-ARP, with DBBM and DBBM-C implanted in the extraction socket, respectively. Cone beam CT (CBCT) was performed before and 6 months after the surgery for assessing changes of hard tissue. Intraoral scanning was performed before and at 2 weeks, 1 month, 3 months, and 6 months after the surgery for assessing soft tissue contour changes and patterns in both groups.Results:After 6 months of healing, the central bone height increased by (8.35±2.25) mm in the DBBM group and (7.70±2.36) mm in the DBBM-C group. The ridge width at 1 mm apically from the higher bone crest increased by 6.43 (-0.76,7.96) mm in the DBBM group and 6.01 (5.41,7.90) mm in the DBBM-C group. There was no statistically significant difference in the changes of bone height and width between the two groups (all P>0.05). In terms of soft tissue contour changes, although the buccal contour collapses were less in the DBBM-C group, the two groups showed no statistically significant difference (all P>0.05). Conclusions:Within the limitations of this study, it was demonstrated that the clinical effects of MCF-ARP using xenogenic bone graft materials with or without collagen components in molars with severe periodontitis were comparable.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.

Guided by the theory of "kidney generates marrow"， the study elaborates the viewpoint that the route of Yin Heel Channel （阴跷脉） is consistent with the "kidney-marrow-brain" axis from the perspective of the circulation of the meridians and the relationship between the zang-fu organs. Accordingly， it is believed that disease of Yin Heel Channel and dysfunction of the "kidney-marrow-brain" axis are the core pathogenesis of children enuresis， and it is elaborated from the following three major aspects， firstly， insufficient kidney essence， dysfunction of the "kidney-marrow-brain" axis， secondly， disease of Yin Heel Channel and deficiency and cold in lower jiao， and thirdly， disease of Yin Heel Channel and loss of nourishment of Chong Vessel. It is proposed to use the mode of "firstly needle， secondly moxibustion， and lastly consolidation" to treat children enuresis. Needle is to adjust yin and yang， warm yang and tonify kidney， and wake up the brain and open the orifices. The acupoints in Yin Heel Channel such as Zhaohai （KI 6）， Jiaoxin （KI 8） and confluence points of the eight extraordinary vessels such as Waiguan （TE 5）， Zulinqi （GB 41） are used， together with Baihui （GV 20）， Yintang （EX-HN 3）， Guanyuan （CV 4）， Qixue （KI 13）， Dazhong （KI 4）. Moxibustion is to reinforce healthy qi and warm yang， bank up the root and consolidate the original qi by moxibustion at Shenque （CV 8）， Mingmen （GV 4）， and Xuanshu （GV 5）. Consolidation is to use acupoints application to consolidate the therapeutic effect， and Guanyuan （CV 4） & Pangguangshu （BL 28）， Qihai （CV 6） & Zhishi （BL 52）， and Shenque （CV 8） & Ciliao （BL 32） are commonly used as the three groups of acupoints to warm the kidney and stop collapse， regulate and tonify the qi and blood.