ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）/cysteinyl aspartate-specific proteinase （Caspase）-1/gasdermin D （GSDMD） signaling pathway. MethodsForty db/db mice were randomly assigned into model， positive control （0.001 3 g·kg·d^-1 dapagliflozin suspension）， and high-， medium-， and low-dose Gelian Tiaotang pills （3.12， 1.56， and 0.78 g·kg·d^-1 suspension of Gelian Tiaotang pills， respectively） groups， with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water， while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose （FBG） and body mass were measured every 4 weeks. Kidneys were weighed after sampling， and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The pathological changes， extracellular matrix deposition， and renal fibrosis degree were examined by hematoxylin-eosin， periodic acid-schiff （PAS）， and Masson staining， respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-1β and IL-18 in the renal tissue. Immunohistochemistry （IHC） was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， and GSDMD-N in the renal tissue. ResultsCompared with the normal group， the model group generally had poor general states and increases in the body mass， kidney weight， kidney index， and levels of FBG， TG， TC， SCr， and BUN （P<0.01）. In addition， glomerular pyknosis， increased matrix， vacuolar degeneration of renal tubular epithelial cells， and interstitial infiltration of inflammatory cells were observed in the model group （P<0.01）， together with rises in the levels of IL-1β and IL-18 in the renal tissue （P<0.01） and up-regulated protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.01）. Compared with the model group， 12 weeks of drug interventions reduced the body mass， kidney weight， and kidney index and lowered the levels of FBG， TG， TC， SCr， and BUN in the serum and IL-1β and IL-18 in the renal tissue （P<0.05， P<0.01）. Furthermore， drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.05， P<0.01）. The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway， thus delaying the process of renal fibrosis in diabetes.

BACKGROUND: Hypertension is a serious chronic disease that can significantly lead to various cardiovascular diseases, affecting vital organs such as the heart, brain, and kidneys. Our goal is to predict the risk of new onset hypertension using machine learning algorithms and identify the characteristics of patients with new onset hypertension. METHODS: We analyzed data from the 2011 China Health and Nutrition Survey cohort of individuals who were not hypertensive at baseline and had follow-up results available for prediction by 2015. We tested and evaluated the performance of four traditional machine learning algorithms commonly used in epidemiological studies: Logistic Regression, Support Vector Machine, XGBoost, LightGBM, and two deep learning algorithms: TabNet and AMFormer model. We modeled using 16 and 29 features, respectively. SHAP values were applied to select key features associated with new onset hypertension. RESULTS: A total of 4,982 participants were included in the analysis, of whom 1,017 developed hypertension during the 4-year follow-up. Among the 16-feature models, Logistic Regression had the highest AUC of 0.784(0.775∼0.806). In the 29-feature prediction models, AMFormer performed the best with an AUC of 0.802(0.795∼0.820), and also scored the highest in MCC (0.417, 95%CI: 0.400∼0.434) and F1 (0.503, 95%CI: 0.484∼0.505) metrics, demonstrating superior overall performance compared to the other models. Additionally, key features selected based on the AMFormer, such as age, province, waist circumference, urban or rural location, education level, employment status, weight, WHR, and BMI, played significant roles. CONCLUSION We used the AMFormer model for the first time in predicting new onset hypertension and achieved the best results among the six algorithms tested. Key features associated with new onset hypertension can be determined through this algorithm. The practice of machine learning algorithms can further enhance the predictive efficacy of diseases and identify risk factors for diseases.
Humans ; China/epidemiology* ; Hypertension/diagnosis* ; Machine Learning ; Male ; Female ; Middle Aged ; Adult ; Nutrition Surveys ; Algorithms ; Aged ; Risk Factors

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.

Objective To study the application value of CAD/CAM technology in the teaching of inlay manufacturing.Methods A total of 60 undergraduates interned in the Department of Stomatology,Yan'an Hospital,Kunming Medical University were randomly divided into an experimental group(n=30)and a control group(n=30).We selected appropriate clinical cases for students to prepare for mandibular molar's proximal occlusal inlays.The instructor guided the results of the first preparation in different ways,and the students made the second modification and preparation,and the assessment team scored and evaluated the five aspects of the final preparation,the shape of the preparation,the shape of the occlusal surface,the dovetail retention,and the adjacent surface.Results The scores of all detection indexes in the experimental group were higher than those in the control group(P<0.05).Conclusion The application of CAD/CAM technology in inlay manufacturing teaching can effectively improve students'clinical hands-on ability and achieve better teaching effects than traditional teaching methods.

Diabetic gastroparesis （DGP） is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically， it often manifests as abdominal distension， nausea and vomiting， early satiety， dyspepsia， etc. The pathogenesis of DGP is multifactorial， closely related to many factors， such as chronic hyperglycemia， neuropathy， autonomic nervous system disorders， inflammation， and oxidative stress. These factors can interact with each other， leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine （TCM） has significant advantages in the prevention and treatment of DGP， including a long history， remarkable efficacy， individualized treatment， diverse therapeutic formulations， and improvement in the quality of life. Additionally， TCM is known for its low adverse reactions， good tolerance， and multi-targeted effects， making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones， inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and modulation of related signaling pathways such as stem cell factor （SCF）/cellular growth factor receptor （c-Kit）， adenosine monophosphate-activated protein kinase （AMPK）， Ras homologous genome member A （RhoA）/Rho-associated coiled-coil forming kinase （ROCK）. This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and regulation of related signaling pathways， aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P＜0.01),increased foot swelling(P＜0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P＜0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P＜0.05);reduction in foot swelling(P＜0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P＜0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.