ObjectiveTo investigate the effects of Xixintang （XXT）-medicated serum on the amyloid β-protein （Aβ）_25-35-induced polarization of BV-2 microglial cells by a cell experiment and uncover the potential mechanisms of this formula in the prevention and treatment of Alzheimer's disease （AD）， thus providing scientific evidence for the clinical application of XXT. MethodsBV-2 microglial cells were subcultured. The optimal concentrations of XXT-medicated serum and Aβ_25-35 were determined via the cell-counting kit-8 （CCK-8） assay. The cell experiment was carried out with the following groups： blank control， model （Aβ_25-35 at 40 μmol·L^-1）， XXT-medicated serum （Aβ_25-35 at 40 μmol·L^-1 + 10% XXT-medicated serum）， and blank serum （Aβ_25-35 at 40 μmol·L^-1 + 10% blank serum）. After 24 hours of cell incubation， immunofluorescence was used to detect the expression of ionized calcium-binding adaptor molecule 1 （IBA1）， CD16/32， and CD206. Real-time PCR was performed to measure the mRNA levels of CD206， CD163， inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg-1）. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of nerve growth factor （NGF）， iNOS， and Arg-1. The nitric oxide （NO） concentration was determined via the nitrate reductase method. ResultsCompared with the blank control group， the model group showed increased expression of IBA1 and CD16/32 （P<0.01）， decreased expression of CD206 （P<0.05）， upregulation in the mRNA level （P<0.01） and content （P<0.05） of iNOS， downregulation in the mRNA levels of CD206， CD163， and Arg-1 （P<0.05， P<0.01）， lowered levels of Arg-1 and NGF （P<0.05）， and an elevation in the NO level （P<0.05）. Compared with the model group， the XXT-medicated serum group exhibited reduced expression of IBA1 and CD16/32 （P<0.05， P<0.01） and increased expression of CD206 （P<0.01）. Both the content and mRNA level of iNOS were downregulated （P<0.05， P<0.01）， while the mRNA levels of CD206， CD163， and Arg-1 were upregulated （P<0.01） in the XXT-medicated serum group. In addition， the XXT-medicated serum group showed elevated levels of Arg-1 and NGF （P<0.05） and a lowered level of NO （P<0.05）. The blank serum group showed no statistically significant differences in the measured parameters compared with the model group. ConclusionThe XXT-medicated serum can inhibit the polarization toward the M1 phenotype and promote the polarization toward the M2 phenotype， exerting anti-inflammatory and neurotrophic effects.

ObjectiveTo explore the potential mechanism of Xixin Decoction （洗心汤， XD） in treating Alzheimer's disease （AD）. MethodsXD-containing serum was prepared， and the BV-2 microglial cell viability was assessed using the CCK8 assay to determine the optimal intervention concentrations of XD-containing serum and amyloid-beta _25-35 （Aβ_25-35） for subsequent experiments. BV-2 cells were divided into four groups， control group， model group （Aβ_25-35）， XD-containing serum group （Aβ_25-35+ XD-containing serum）， and blank serum group （Aβ_25-35 + blank serum）. After 24 hours of culture， the levels of interleukin-1β（IL-1β）， cyclooxygenase-2 （COX-2）， and arginase-2 （Arg-2） in the supernatent were detected by ELISA. Immunofluorescence staining was performed to detect the protein levels of ionized calcium-binding adaptor molecule 1 （IBA1）， CD86， and CD206. RT-PCR was used to analyze the mRNA expression of IL-1β， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. ResultsThe concentrations of 10% XD-containing serum and 40 μmol·L^-¹ Aβ_25-35 were selected for subsequent experiments. Compared to the control group， the model group showed significantly increased levels of IL-1β and COX-2 in the supernatant， as well as elevated protein expression of IBA1 and CD86 and increased mRNA expression of IL-1β and IL-6， while exhibiting significantly reduced levels of Arg-2 in the supernatant， CD206 protein expression， and IL-10 mRNA expression （P＜0.05 or P＜0.01）. Compared to the model group， the XD-containing serum group showed significant improvement in all these indicators （P＜0.01）， whereas no statistically significant differences were observed in the blank serum group （P＞0.05）. ConclusionXD may regulate microglial activation， inhibit pro-inflammatory factors， and enhance anti-inflammatory factor release， thereby improving neuroimmune inflammation and inhibiting the progression of Alzheimer's disease.

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 The biomechanical model for the musculoskeletal system of a human knee joint was established using a numerical simulation method.The kinematic and dynamic information captured during jumping motion simulated by the human dynamic model was used as driven data of the knee biomechanical model,followed by further analysis of the stress field distribution characteristics of the meniscus under different thermal-force coupling knee brace conditions.Methods Based on computed tomography and magnetic resonance imaging of the subject,a realistic human knee model,including bone,articular cartilage,meniscus,ligaments and peripheral soft tissues of the knee joint,was constructed.Furthermore,two gaits,namely taking-off and landing-on,of jumping motion with an increased risk of meniscus injuries were selected according to mechanical features in full-cycle jumping motion.Subsequently,the stress field characteristics of the knee meniscus under four different thermal-force coupling knee braces were analyzed,the changes of the peak stress of the meniscus and its stress concentration area were discussed,and the protective efficacy and mechanical basis of meniscal injuries and wearing knee braces were explored.Results The anterior part of the medial knee meniscus was a vulnerable area under concentrated stress.Under the knee brace thermal-force coupling condition,the stress concentration area of the medial meniscus was transferred from its narrow and weak anterior part to its wide and thick middle part,and the peak stress was also significantly reduced.The peak stress on the medial meniscus and that on the lateral meniscus were similar,indicating that the two parts of the meniscus bore the external load evenly,and the meniscus stress concentration area decreased.Conclusions Thermal-force coupling knee braces have good protective effects against knee meniscus injury.The numerical simulation provides theoretical support and technical guidance for the design of multifunctional thermal knee braces.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Objective:To estimate the influence of metabolic parameters in 18F-FDG PET/CT and clinically relevant indicators on the prognosis of patients with cervical cancer. Methods:A total of 174 patients with cervical cancer (age (53.6±11.1) years) who underwent baseline 18F-FDG PET/CT examination in the Affiliated Hospital of Qingdao University from May 2011 to December 2020 were retrospectively collected. Metabolic parameters (metabolic tumor volume of primary lesion (MTV p), total lesion glycolysis of primary lesion (TLG p), MTV sum of total lesions (MTV total) in the whole body, TLG sum of total lesions (TLG total)) and clinical parameters (International Federation of Gynecology and Obstetrics (FIGO) stage, tumor maximum diameter ( Dmax), et al) were collected. Cox regression and Kaplan-Meier method were performed to evaluate the prognostic and predictive values of those parameters. Results:The follow-up time was 6-120 months, during which 52 patients (29.9%, 52/174) developed progression. The 5-year overall survival (OS), progression-free survival (PFS), local control (LC) and distant metastasis-free survival (DMFS) rates were 83.3%(145/174), 70.1%(122/174), 75.3%(131/174) and 82.8%(144/174), respectively. Cox regression showed that FIGO stage and MTV total were independent factors for predicting PFS, OS and LC (hazard ratio ( HR): 1.005-11.605, all P<0.05). FIGO stage and TLG total were independent factors for predicting DMFS ( HR: 1.002-12.258, all P<0.05). Conclusion:MTV total and FIGO stage are effective predictors of patients with cervical squamous cell carcinoma.

Objective:To explore the mechanism of peritoneal dialysis solution (PDS)-induced peritoneal microinflammation through activation of ceramide (CER) in peritoneal dialysis model mice.Methods:Thirty 5-week-old male C57BL/6 mice weighing about 22 g were used to set up peritoneal dialysis models, and then were randomly divided into 4 groups: sham operation group (1.5 ml sterilized water, n=7), high glucose-PDS group (1.5 ml 4.25% PDS, n=8), high glucose-PDS+ acid sphingomyelinase (ASMase) inhibitor desipramine (DES) group (1.5 ml sterilized water+10 mg/kg DES, n=8), high glucose-PDS+Src kinase inhibitor PP2 group (1.5 ml sterilized water +1 mg/kg PP2, n=7), with intraperitoneal injection once a day. After 28 days, the mice were sacrificed to retain peritoneal tissues. HE staining and Masson staining were used to observe the histological changes of peritoneum. Immunohistochemistry was used to detect the Toll-like receptor 4 (TLR4) and macrophages. High performance liquid chromatography, liquid chromatography/mass spectrometry and immunofluorescence were used to detect the expression of ASMase and CER. Real-time quantitative PCR was used to detect the mRNA levels of c-Src, p-Src, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blotting was used to detect the protein levels of c-Src, and p-Src. Enzyme-linked immunosorbent assay was used to detect the serum C reactive protein (CRP), IL-6 and TNF-α. Results:(1) High glucose-PDS led to peritoneal hyperplasia, collagen deposition and fibrosis in the peritoneal dialysis mice, indicating successful modeling. Compared with high glucose-PDS group, peritoneal hyperplasia, collagen deposition and fibrosis of mice treated with DES and PP2 were significantly improved (all P<0.05). (2) Compared with sham operation group, ASMase activation and CER level of peritoneal tissues were significantly higher in high glucose-PDS group, and DES could significantly inhibit activated ASMase and increased CER expression caused by high glucose-PDS (both P<0.05). PP2 had no significant effect on ASMase activation and CER level (both P>0.05). (3) Compared with sham operation group, there were more TLR4 and macrophage positive staining cells in peritoneal tissues in high glucose-PDS group, and the mRNA expression levels of IL-6 and TNF-α in peritoneal tissues and serum CRP, IL-6 and TNF-α were higher (all P<0.05). DES and PP2 could significantly inhibit the increased TLR4, macrophages and related inflammatory factors induced by high glucose-PDS (all P<0.05). (4) Compared with sham operation group, c-Src and p-Src mRNA and protein expression levels of peritoneal tissues in high glucose-PDS group were significantly higher (all P<0.05). PP2 significantly inhibited the increased p-Src mRNA and protein levels caused by high glucose-PDS (both P<0.05), but had no significant effect on the mRNA and protein expression levels of c-Src (both P>0.05). DES had no significant effect on the mRNA and protein expression levels of c-Src and p-Src (all P>0.05). Conclusions:High glucose-PDS may enhance the expression of CER through stimulating the activity of ASMase, phosphorylate Src, activate TLR4 and induce inflammatory damage of peritoneum in peritoneal dialysis model mice.

Objective:To investigate the relationship between common functional gastrointestinal diseases symptoms with psychological factors, diet and lifestyles by using the network analysis method which has achieved great success in the field of psychology in recent years.Method:A questionnaire survey was conducted in two military units using the cluster sampling method during July 2020, and a total of 1 805 subjects were included. Functional gastrointestinal disease symptoms were evaluated with the Gastrointestinal Symptom Rating Scale (GSRS). The state, trait anxiety scale and stress response scale were used to evaluate the mental and psychological state by self-evaluation. R was used to build the network and calculate statistical parameters.Results:1 486 of the 1 805 subjects (82.3%) had experienced functional gastrointestinal diseases symptoms within 2 weeks, but most of them were mild. Network analysis shows that there was a strong interaction between digestive system symptoms with different clinical manifestations (Spearman coefficient ranges 0.31-0.56). There was a clear relationship between functional gastrointestinal symptoms and mental and psychological factors (Spearman coefficient ranges 0.16-0.27), but there was no clear interaction with diet, age, education level, body mass index, etc. Functional gastrointestinal diseases symptoms were connected with mental and psychological factors through two nodes: stress and indigestion. The stability coefficient of node strength correlation was 0.75, indicating that the network was stable.Conclusions:The current study revealed the network structure and features of functional gastrointestinal diseases symptoms with mental and psychological factors. The key linking nodes provided potential interfering target for controlling functional gastrointestinal symptoms related to mental and psychological factors.

Objective:To investigate the clinical application of cervix-uterine internal target volume (ITV) in volume-modulated arc therapy (VMAT) for cervical cancer under different bladder filling conditions, aiming to obtain more accurate planning target volume (PTV).Methods:Sixty-two patients with cervical cancer receiving radiotherapy rather than surgery were selected and randomly divided into the study ( n=31) and control groups ( n=31). In the study group, individualized ITV, PTV and PTV margin were obtained under three bladder filling status by localization CT scan to compare the VMAT. The target area and organs at risk (OARs) within the target area were statistically compared between two groups. The target missing rate in CBCT, adverse events and short-term efficacy of radiotherapy were analyzed in two groups. Results:There was no significant difference in the volume of target area and OARs in the target area between two groups (both P>0.05). In the study group, the target missing rate and target missing volume were significantly lower compared with those in the control group (both P<0.05). There was no significant difference in the incidence of acute radiation-induced adverse events between two groups ( P>0.05). The 1-, 2-year overall survival and progress-free survival did not significantly differ between two groups (all P>0.05). One patient in the study group had uterine recurrence and 2 cases in the control group. Conclusion:Application of individualized cervix-uterine ITV and PTV in definitive VMAT under different bladder filling conditions can improve the accuracy of target area contouring and improve the local control rate in cervical cancer patients.

Objective To observe the effect of air mattress bed on the quality of chest compression during cardiopulmonary resuscitation (CPR). Methods This was a self-controlled study and included twenty formally CPR-trained doctors. According to the 2015 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, chest compression was randomly tested on a manikin for two minutes in A, B, C group. Group A was tested in ordinary bed, group B was compress in air mattress and hard backboard, and group C was tested in air mattress bed. There was a ten minutes rest between each compression. All compression data, including compression rate, depth, incomplete recoil and shallow number, were collected via real-time feedback device. Statistical analysis was performed using SPSS 22.0. Multiple groups were compared with One-way ANOVA and within groups were compared with t test. The enumeration data was analyzed by chi-square test. Results There was no statistically significant difference between groups in mean chest compression rates (107.9±5.1 vs. 107.7±4.56 vs. 109.7±4.86, P=0.6). Mean compression depth was significantly better in group A and B than in group C [(53.45±2.04) mm and (52.65±2.13) mm vs. (48.45±1.36) mm, all P<0.05)]. The number of shallow compression in group C was significantly higher than those in group A and B [(97.3±23.4) vs. (23.6±19.3) and (35.3±33.9), all P<0.05)]. The retention rates in group A was better than those in group B and C [(58.43±4.17％) vs. (62.51±4.37)％ and (62.63±4.22)％, all P<0.05]. The compression depth of group C in the second minute was significantly less than that in the first minute (46.45±1.43 mm vs. 50.05±1.64 mm, P<0.05), and the number of shallow compression was more than the first minute (62.1±16.4 vs. 35.3±8.5, P<0.05). Significant difference in accuracy was observed among the three groups (33.64％ vs. 28.66％ vs. 19.24％, P<0.05). Conclusions The use of air mattress bed in CPR has a significant impact on the quality of manual chest compression. Eliminating the elasticity of air mattress bed would effectively improve the quality of chest compressions.