ObjectiveTo construct an actor-network for integrating physical activity into rehabilitation services based on the World Health Organization Rehabilitation in Health Service System framework and actor-network theory (ANT). MethodsContent analysis was employed using the six building blocks of health service systems as the theoretical framework. Actors related to rehabilitation services were extracted and categorized into a rehabilitation actor pool, while a physical activity actor pool was formed based on four major physical activity scenarios. Actors from both pools were integrated, deduplicated and classified to form a final list of integrated actors. Using ANT, the construction process of the actor network integrating physical activity into rehabilitation was analyzed through the four stages of translation: problematization, interessment, enrollment and mobilization. ResultsA dynamic integration network was constructed, comprising human actors (patients, rehabilitation professionals, researchers, sports coaches, government departments, medical institutions, community organizations and industry media, etc.) and non-human actors (assistive devices, sports infrastructure, smart equipment, information systems, online exercise guidance systems, laws and regulations, strategic documents, and exercise prescriptions, etc.). The study identified maximizing rehabilitation outcomes as the mandatory passage point and elaborated on the critical role of government departments as focal actors in coordinating various stakeholders. ConclusionThe integration of physical activity into rehabilitation services is a dynamic network constructed by diverse actors through a process of translation. ANT provides an operational theoretical framework for cross-departmental governance of rehabilitation policies in China, promotes the spatial expansion of the rehabilitation field, and drives its transformation toward a networked and ecological system. The government needs to play a leading role in facilitating role reconstruction and synergy among heterogeneous actors in both the sports and rehabilitation sectors through mechanism design, to create a bidirectional empowerment mechanism that fosters mutual progress and ensures the sustainable development of integrated services.

ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

BACKGROUND: Cervical squamous cell carcinoma (CESC), the most common subtype of cervical cancer, is primarily caused by the high-risk human papillomavirus (HPV) infection and genetic susceptibility. Single-cell RNA sequencing (scRNA-seq) has been widely used in CESC research to uncover the diversity of cell types and states within tumor tissues, enabling a detailed study of the tumor microenvironment (TME). This technology allows precise mapping of HPV infection in cervical tissues, providing valuable insights into the initiation and progression of HPV-mediated malignant transformation. METHODS: We performed the scRNA-seq to characterize gene expression in tumor tissues and paired adjacent para-cancerous tissues from four patients with early-stage CESC using the 10× Genomics platform. The HPV infection and its subtypes were identified using the scRNA data and viral sequence mapping, and trajectory analyses were performed using HPV+ or HPV- cells. Interactions between different types of keratinized cells and their interactions with other cell types were identified, and pathways and specificity markers were screened for proliferating keratinized cells. The Cancer Genome Atlas (TCGA) dataset was used to verify the prognostic correlation between tumor-specific PI3+S100A7+ keratinocyte infiltration and CESC, and the localization relationship between PI3+S100A7+ keratinocytes and macrophages was verified by immunofluorescence staining. RESULTS: Various types of keratinocytes and fibroblasts were the two cell types with the most significant differences in percentage between the tumor tissue samples and paired adjacent non-cancerous tissue samples in the early stages of CESC. We found that PI3+S100A7+ keratinocytes were associated with early HPV-positive CESC, and PI3+S100A7+ keratinocytes were more abundant in tumors than in adjacent normal tissues in the TCGA-CESC dataset. Analysis of clinical information revealed that the infiltration of PI3+S100A7+ keratinocytes was notably higher in tumors with poor prognosis than in those with good prognosis. Additionally, multiplex immunofluorescence analysis showed a specific increase in PI3+S100A7+ expression within tumor tissues, with PI3+S100A7+ keratinocytes and CD163+ macrophages being spatially very close to each other. In the analysis of cell-cell interactions, macrophages exhibited strong crosstalk with PI3+S100A7+ proliferating keratinocytes in HPV-positive CESC tumors, mediated by tumor necrosis factor (TNF), CCL2, CXCL8, and IL10, highlighting the dynamic and tumor-specific enhancement of macrophage-keratinocyte interactions, which are associated with poor prognosis and immune modulation. Using CIBERSORTx, we discovered that patients with high infiltration of both PI3+S100A7+ proliferating keratinocytes and macrophages had the shortest overall survival. In the analysis of cell-cell interactions, PI3+S100A7+ proliferating keratinocytes and macrophages were found to be involved in highly active pathways that promote differentiation and structure formation, including cytokine receptor interactions, the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and TNF signaling pathway regulation. Further subtyping of fibroblast populations identified four subtypes. The C1 group, characterized by its predominance in tumor tissues, is a subtype enriched with cancer-associated fibroblasts (CAFs), whereas the C3 group is primarily enriched in adjacent non-cancerous tissues and consists of undifferentiated cells. Moreover, the distinct molecular and cellular differences between HPV16- and HPV66-associated tumors were demonstrated, emphasizing the unique tumor-promoting mechanisms and microenvironmental influences driven by each HPV subtype. CONCLUSIONS We discovered a heterogeneous population of keratinocytes between tumor and adjacent non-cancerous tissues caused by HPV infection and identified macrophages and specific CAFs that play a crucial role during the early stage in promoting the inflammatory response and remodeling the cancer-promoting TME. Our findings provide new insights into the transcriptional landscape of early-stage CESC to understand the mechanism of HPV-mediated malignant transformation in cervical cancer.
Humans ; Female ; Papillomavirus Infections/genetics* ; Uterine Cervical Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Keratinocytes/metabolism* ; Single-Cell Analysis/methods* ; Tumor Microenvironment/genetics*

OBJECTIVE To explore the correlation between phosphatidylinositol-3-kinase alpha(PIK3CA)gene mutation and the clinicopathological characteristics of Epstein-Barr virus(EBV)infection in patients with gastric cancer.METHODS Cancer tissue samples were collected from 593 patients with gastric cancer who under-went surgery at the Affiliated Hospital of Hebei University between Sep.2021 and Sep.2024.EBV infection in pa-tients with gastric cancer was detected by EBV-encoded RNA(EBER)in situ hybridization.Based on the detec-tion results,patients were divided into an EBV-positive group(n=31)and an EBV-negative group(n=562).The incidence of EBV-infected gastric cancer was compared among patients of different genders and ages.The relationship between EBV infection and PIK 3CA gene mutation,as well as clinicopathological character-istics of patients with gastric cancer,was analyzed.Spearman's correlation analysis was used to assess the correla-tion between PIK3CA gene mutation and EBV infection in patients with gastric cancer.RESULTS Among the 593 gastric cancer cases,31 were EBER-positive,with a positive rate of 5.23％.EBER showed scattered dot scope or diffuse staining,appearing as a dark brown signal localized in the nucleus.The PIK3CA gene mutation rate was higher in the EBV-positive group(32.26％)than in the EBV-negative group(P＜0.001).PIK3CA gene muta-tions mainly occurred in exons 9 and 20,with 2 cases of p.E542K mutation,5 cases of p.E545K mutation,1 case of pH1047L mutation,no cases of p.H1047R mutation were detected.The proportion of patients with tumors at the esophagogastric junction,T3-T4 invasion depth,and lymph node metastasis was higher in the EBV-positive group than in the EBV-negative group(P＜0.05).There was a positive correlation between PIK 3CA gene muta-tion and EBV infection in patients with gastric cancer(r=0.742,P=0.026).The proportion of EBV infection was higher in male patients with gastric cancer(6.49％)than in females(P＜0.001).CONCLUSIONS The inci-dence of EBV-infected gastric cancer is low,but it is closely related to PIK3CA gene mutation,gender,tumor lo-cation,invasion depth and lymph node metastasis in patients with gastric cancer.

Objective:To evaluate the safety and efficacy of radiofrequency ablation（RFA）in the treatment of papillary thyroid microcarcinoma（PTMC）near and remote from the thyroid capsule.Methods:The clinical data，ultrasound images，ablation parameters and postoperative follow-up metrics were prospectively collected from 130 patients with pathologically confirmed PTMC in the Second Affiliated Hospital of Xi'an Jiaotong University who underwent RFA treatment between January 2023 and December 2024. According to whether the nodule margin was ≤ 2 mm from the thyroid capsule，the patients were divided into the subcapsular group（60 cases）and the remote from the capsule group（70 cases）. The clinical data，ablation parameters，complication rate，absorption of ablation lesions，tumor recurrence and metastasis were compared between the two groups.Results:The success rates of RFA in both groups were 100%. There was a statistically significant difference between the two groups at baseline in the location of nodules（ χ2=13.266， P=0.001）. After 12 months of routine follow-up，the incidence of complications was 5.00%（3/60）in the subcapsular group and 1.43%（1/70）in the remote from the capsule group，all complications recovered within 1 month，with no statistically significant difference（ P=0.407）. There were no significant changes in thyroid function［including free triiodothyronine（FT3），free thyroxine（FT4）and thyroid-stimulating hormone（TSH）］before and one month after RFA in the two groups（all P>0.05）. A statistically significant difference in the volume reduction rate（VRR）between the two groups was observed only when maximum diameter ≤ 5?mm at the 1st and 3rd months（all P<0.05）. For the remaining postoperative follow-up periods，there were no statistically significant differences in ablation zone volume or VRR between the two groups（all P>0.05）. At the final follow-up，for lesions with maximum diameter ≤ 5?mm，the tumor disappearance rate was 100% in both the subcapsular and remote from the capsule groups. For lesions with maximum diameter >5 mm，the rates were 78.4%（29/37）and 89.7%（26/29）in the respective groups，with no statistically significant difference between the two groups（ χ2 = 1.489， P =0.222）.There was no local tumor progression，lymph node metastasis or distant metastasis in either group. Conclusions:RFA is a safe and effective treatment for subcapsular PTMC，demonstrating comparable efficacy to that for PTMC located remote from the thyroid capsule.

Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Immunotherapy ; Lung Neoplasms/genetics* ; Immunosenescence ; Aged

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Primary pulmonary nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare and highly aggressive thoracic malignancy that poses significant diagnostic and therapeutic challenges in clinical practice. This tumor is characterized by its heterogeneous clinical presentations and poor prognosis, often evading accurate initial diagnosis. In this study, we present two cases of primary pulmonary NMC treated with an integrated therapeutic approach combining anti-angiogenic agents, platinum-based chemotherapy, and radiotherapy. This multimodal strategy achieved survival durations of 32 and 13 months, respectively, surpassing the currently reported median survival of advanced NMC. Through a systematic literature review of reported cases, we have summarized the currently used diagnostic methods and treatment modalities for NMC. Our findings suggest that multimodal therapy incorporating anti-angiogenic treatment may offer superior clinical outcomes compared to conventional monotherapy regimens, particularly for patients who are not eligible for surgery. This comprehensive investigation enhances our understanding of NMC management by elucidating diagnostic pitfalls through histopathological correlation and proposing an effective therapeutic combination that demonstrates improved survival outcomes. By providing valuable insights into the diagnosis and treatment of primary pulmonary NMC, we hope to contribute to the development of more effective strategies for managing this rare and aggressive malignancy.
Humans ; Angiogenesis Inhibitors/therapeutic use* ; Carcinoma/therapy* ; Combined Modality Therapy ; Lung Neoplasms/diagnosis* ; Nuclear Proteins ; Oncogene Proteins ; Neoplasm Proteins

Objective:To discuss the infection status and clinical outcomes in the patients with bullous pemphigoid(BP),and to analyze the risk factors for infection in hospitalized BP patients,as well as to construct and evaluate the risk prediction model.Methods:A total of 126 patients first diagnosed with BP were selected.According to the occurrence of infection,the patients were divided into infection group(52 cases)and non-infection group(74 cases).The infection status and outcomes of the patients in two groups were recorded;statistical analysis was performed on the general data,laboratory examination results,FRAIL scale scores for frailty screening,NRS2002 scores,and skin lesion severity of the patients in two groups;multivariate Logistic regression model was used to identify the risk factors for infection in the patients;the goodness-of-fit test was used to evaluate the model;receiver operating characteristic(ROC)curve was used to evaluate the predictive value of the model for infection.Results:Among the 126 hospitalized BP patients,52 cases had infection,with an infection rate of 41.27％.The mortality rate of the patients in infection group was higher than that in non-infection group(P＜0.05),and the remission rate of the patients in non-infection group was higher than that in infection group(P＜0.05).The FRAIL scale score for frailty screening,NRS2002 score,serum albumin level,prealbumin level,number of hospitalization,skin lesion severity,and time of hospital stay of the patients in infection group were significantly higher than those in non-infection group(P＜0.05).The multivariate Logistic regression analysis results derived the regression equation:Logistic(P)=-7.63+0.922× skin lesion severity+2.565×FRAIL scale score for frailty screening+1.214×NRS2002 score.The area under the curve of the Logistic regression model was 0.916.Conclusion:The FRAIL scale score for frailty screening,NRS2002 score,and skin lesion severity are the risk factors for infection in the hospitalized BP patients.The constructed infection risk prediction model based on these factors has good predictive value and may provide new ideas for the prevention and control of infection in the hospitalized BP patients.

Objective:To evaluate the clinical efficacy of autologous costal cartilage combined with nasal Pitanguy ligament reconstruction for correcting downward rotation of the nasal tip following rhinoplasty.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent this combined technique at the Department of Plastic Surgery, Chongqing Contemporary Plastic Surgery Hospital, between January 2019 and January 2021. Autologous costal cartilage was carved into a bifurcated nasal columella support graft (3 cm in length × 8 mm in width × 2 mm in thickness, with a 1 cm bifurcation at the distal end). This graft was fixed across the caudal septum to establish a costal cartilage support framework. A piece of costal perichondrium (approximately 3 cm × 1 cm) was harvested. Using 5-0 PDS sutures, the cephalic end of the perichondrium was meticulously fixed to the residual stump of the Pitanguy ligament on the nasal dorsum, while the caudal end was anchored to the nasal tip scaffold, thereby reconstructing the ligamentous tension system. Postoperative complications were monitored. Preoperatively and at 12 months postoperatively, patients’ photographs were processed using Adobe Photoshop CS 6 to measure the nasolabial angle, nasofrontal angle, and columellar-lobular angle. Patient satisfaction was assessed using the rhinoplasty outcome evaluation (ROE) questionnaire (total score range: 0-24; higher scores indicate greater satisfaction). The paired t-test was employed for statistical comparison of these measurements and scores, with a P-value < 0.05 considered statistically significant. Results:A total of 76 patients were included (16 males, 60 females), with a mean age of 26.5 ± 4.3 years (range: 18-42 years). The mean follow-up duration was 13.2 months (range: 12-15 months). All patients recovered well, with no complications, such as nasal tip graft visibility, graft displacement, or breathing difficulties were observed. Natural contouring between the nasal tip and dorsum was achieved, and the fullness of the infratip lobule was significantly improved. Statistically significant differences ( P < 0.01 for all) were found between preoperative and 12-month postoperative measurements: nasofrontal angle (143.54° ± 5.08° vs. 134.12° ± 8.63°), nasolabial angle (82.28° ± 7.02° vs. 95.36° ± 3.76°), columellar-lobular angle (50.72° ± 6.67° vs. 43.05° ± 4.52°), and ROE scores [(9.05 ± 2.03) points vs. (22.07 ± 2.45)points]. Conclusion:The combined technique utilizing autologous costal cartilage and Pitanguy ligament reconstruction effectively corrects downward rotation of the nasal tip. Through the synergistic action of costal cartilage structural support and anatomical restoration of the Pitanguy ligament, it achieves a natural nasal tip contour, functional stability and high patient satisfaction.