The repair of bone defects is heavily influenced by the dynamic osteogenic microenvironment. Static scaffolds constructed by traditional 3D printing technology cannot simulate the dynamic nature of the microenvironment during bone defect repair due to the fixed structure, uncontrollable release of active factors, and difficult regeneration of blood vessels, among other factors. Breaking through the limitations of these static scaffolds and realizing the intelligent and dynamic regulation of the osteogenic microenvironment is a key scientific issue in the field of bone tissue engineering. 4D printing technology combines the dynamic responsiveness of bone restoration materials with the concept of intelligent design to regulate the micro and macro structure of scaffolds. This technology provides a new method for bone tissue engineering by responding to endogenous and exogenous stimuli and creating a better osteogenic microenvironment through functionalized design, including drug delivery and antibacterial function. However, this technology currently suffers from challenges related to dynamic response material design, insufficient precision of printing technology, and mismatches between multi-stimulus response systems, metabolic rhythms of bone tissue, and functionalized composite scaffolds. Future research should focus on the development of smart response materials with excellent dynamic responses and bioactivity, the creation of new printing technologies, and the design of personalized and precise bone repair solutions. The aim of this paper is to review the current research status of 4D printing for bone tissue engineering in terms of material types, response mechanisms, and applications to provide a theoretical basis for the development and clinical application of functional bone repair materials in the future.

ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

HBV DNA integration （iDNA） is the core barrier that must be overcome to achieve functional cure for chronic hepatitis B （CHB） and to prevent the occurrence of hepatocellular carcinoma （HCC）. During reverse transcription， 5%　—　10% of viral genomes are converted into double-stranded linear DNA that is randomly inserted into host chromosomes， generating stable iDNA and continuously producing HBsAg， thereby driving B- and T-cell immune exhaustion and locking the host in an immune-tolerant state. The process of iDNA runs throughout the entire natural history of HBV infection， and the viral enhancers it carries can promote clonal hyperplasia of indeterminate potential， accumulate pre-neoplastic mutations， and ultimately lead to HCC. Although long-term nucleos（t）ide analog or interferon therapy can suppress viral replication and reduce the formation of new integrations， existing therapies still fail to eliminate existing iDNA. Therefore， there is an urgent need for innovative strategies that can precisely target integration breakpoints， epigenetically silence iDNA， or eradicate integrated clones， so as to significantly increase the functional cure rate of CHB and fundamentally reduce the risk of HCC.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

ObjectiveTo investigate the expression of C1q tumor necrosis factor-related protein 3 （C1QTNF3） in liver cancer tissue， its association with the clinicopathological features of patients， and its potential value in predicting the prognosis of liver cancer. MethodsRelated data were collected from TIMER， UALCAN， TNMplot， and GEO databases， and the bioinformatics methods were used to measure the expression level of C1QTNF3 in pan-cancer， normal tissue/liver cancer tissue， and cancerous tissue/paracancerous tissue. Cancerous and paracancerous tissue samples were collected from 90 patients with liver cancer， and related clinical data were collected， including age， sex， tumor diameter， and tumor number. The independent-samples t test or the paired t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used to investigate the association between the expression level of C1QTNF3 and the survival of patients with liver cancer. The Cox regression model was used to identify the risk factors for the prognosis of patients with liver cancer， and the receiver operating characteristic （ROC） curve was used to analyze the ability of C1QTNF3 expression at different time points for predicting the prognosis of patients with liver cancer. ResultsThe bioinformatics analysis showed that the expression of C1QTNF3 was upregulated in various malignant tumors， especially in liver cancer tissue （P<0.001）， and the expression level of C1QTNF3 in liver cancer tissue was significantly higher than that in normal tissue and paracancerous tissues （all P<0.01）. The immunohistochemical staining results of 90 patients with liver cancer showed that C1QTNF3 was mainly expressed in cytoplasm， with a small amount in nucleus， and it had negative expression in paracancerous tissue and positive expression in liver cancer tissue. The positive expression rate and strong positive expression rate of C1QTNF3 protein in liver cancer tissue were significantly higher than those in paracancerous tissue （positive expression rate： 76.67% vs 33.33%， χ²=34.141， P<0.01； strong positive expression rate： 54.44% vs 5.56%， χ²=51.217， P<0.01）. The liver cancer patients with a tumor diameter of ≥5 cm， an advanced stage， the presence of liver cirrhosis， negative HBsAg， and gamma-glutamyl transpeptidase （GGT）≥50 U/L had a significantly higher strong positive expression rate of C1QTNF3 protein than those with a tumor diameter of <5 cm， an early stage， the absence of liver cirrhosis， positive HBsAg， and GGT<50 U/L （all P<0.05）. The univariate Cox regression analysis showed that tumor diameter， recurrence， and C1QTNF3 expression were influencing factors for the prognosis of patients with liver cancer （all P<0.05）， and the multivariate Cox regression analysis showed that the expression level of C1QTNF3 and recurrence were independent risk factors for the survival of patients with liver cancer （both P<0.05）. The survival curve analysis showed that for all patients with liver cancer， the patients with high （strong positive） expression of C1QTNF3 had significantly lower overall survival rate and disease-free survival rate than those with low expression （χ²=17.010 and 13.647， both P<0.001）； for liver cancer patients with a tumor diameter of ≥5 cm， an early/advanced stage， recurrence， the presence of liver cirrhosis， positive HBsAg， alanine aminotransferase （ALT） <40 U/L， ALT≥40 U/L， and GGT≥50 U/L， the patients with high expression of C1QTNF3 had a significant reduction in overall survival rate （χ²=11.086， 5.578， 5.295， 19.159， 16.391， 13.774， 10.119， 8.152， and 12.035， all P<0.05）. The ROC curve analysis showed that C1QTNF3 expression had the strongest predictive potential at 5 years， with an area under the ROC curve of 0.77. ConclusionC1QTNF3 is highly expressed in liver cancer tissue， and the expression level of C1QTNF3 and recurrence are closely associated with the survival of patients with liver cancer. Patients with high expression of C1QTNF3 protein tend to have a lower survival rate.

ObjectiveTo investigate the effect of gallic acid （GA） on the proliferation， migration， invasion， and apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism. MethodsHepG2 cells were treated with different concentrations of GA （0， 5， 10， 20， 30， 40， and 50 μg/mL） for 24 and 48 hours， and CCK8 assay was used to measure cell viability and calculate IC₅₀. The experiment was divided into control group （HepG2 cells）， 5 μg/mL GA group， 10 μg/mL GA group， and 20 μg/mL GA group. Plate colony formation assay was used to evaluate the effect of GA on cell proliferation； wound healing assay and Transwell chamber assay were used to observe the effect of GA on cell migration and invasion； flow cytometry was used to observe the effect of GA on cell apoptosis； Western blot was used to measure the expression of matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-9 （MMP-9）， and apoptosis-related proteins. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe mean IC₅₀ value of GA on HepG2 cells was 38.02±2.58 μg/mL at 24 hours and 18.36±1.54 μg/mL at 48 hours. The number of cell colonies was 239.00±29.45 in the control group， 210.00±19.00 in the 5 μg/mL GA group， 144.33±16.03 in the 10 μg/mL GA group， and 57.00±9.55 in the 20 μg/mL GA group， suggesting that compared with the control group， each GA group had a significant reduction in cell colony formation ability （all P<0.05）. After 24 hours of treatment， the cell migration rate was 42.62%± 7.82% in the control group， 35.34%±6.42% in the 5 μg/mL GA group， 21.85%±4.42% in the 10 μg/mL GA group， and 12.57%± 3.54% in the 20 μg/mL GA group， respectively， in these four groups， and the number of transmembrane cells in these four groups was 230.30±15.30， 182.12±12.60， 137.20±7.50， and 124.40±6.80， respectively， suggesting that compared with the control group， each GA group had significant reductions in migration rate and the number of transmembrane cells （all P<0.05）. After 48 hours of treatment， the cell apoptotic rate was 0.67%±0.08% in the control group， 13.27%±1.07% in the 5 μg/mL GA group， 20.94%± 2.45% in the 10 μg/mL GA group， and 40.74%±2.63% in the 20 μg/mL GA group， and compared with the control group， each GA group had a significant increase in cell apoptosis rate （all P<0.05）. Compared with the control group， each GA group had significant reductions in the protein expression levels of MMP-2 and MMP-9 （all P<0.05） and significant increases in the protein expression levels of Bax and cleaved caspase-3 （all P<0.05）. ConclusionGA can inhibit the proliferation， migration， and invasion of HepG2 cells and promote the apoptosis of HepG2 cells， possibly by regulating MMP-2， MMP-9， and the apoptosis-related proteins Bax/Bcl-2.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

BackgroundPatients with schizophrenia experience low quality of life， and internalized stigma is considered an important indicator for quality of life， while the mediating role of self-esteem and severity of negative symptoms in the relationship between internalized stigma and quality of life remains underexplored. ObjectiveTo examine the mediating role of self-esteem and severity of negative symptoms in the relationship between internalized stigma and quality of life， so as to provide references for improving their quality of life. MethodsA total of 342 patients with schizophrenia who were hospitalized in 6 hospitals in Xiangyang City， Siping City and Changchun City from April to September 2023 were included， and all of whom met the diagnostic criteria for schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10）. Internalized Stigma of Mental Illness Scale （ISMI）， Schizophrenia Quality of Life Scale （SQLS）， Self-Esteem Scale （SES） and negative symptom subscale of Positive and Negative Symptom Scale （PANSS） were administered to all patients. Spearman correlation analysis was adopted to determine correlations between the different scales. A structural equation modeling was constructed using Amos 28.0， and Bootstrap method was employed to verify the mediating effect of self-esteem and negative symptom severity in the association between internalized stigma and quality of life. ResultsA total of 309 patients （90.35%） completed questionnaires in this study. The ISMI score of schizophrenia patients was positively correlated with both SQLS score and the PANSS negative symptom subscale score （r=0.612， 0.492， P<0.01）， while was negatively correlated with SES score （r=-0.513， P<0.01）. The SQLS score was negatively associated with the SES score （r=-0.555， P<0.01） and positively associated with PANSS negative symptom subscale score （r=0.672， P<0.01）. The SES score was negatively correlated with PANSS negative symptom subscale score （r=-0.433， P<0.01）.The total effect value of internalized stigma on quality of life was 0.746 （95% CI： 0.680~0.806）. Self-esteem and severity of negative symptoms independently mediated the relationship between internalized stigma and quality of life， and the indirect effect values were 0.151 （95% CI： 0.062~0.254） and 0.126 （95% CI： 0.047~0.205）， accounting for 20.24% and 16.89% of the total effect， respectively. In addition， a chained mediation effect of self-esteem and quality of life was also demonstrated， the indirect effect value was 0.102 （95% CI： 0.049~0.165）， accounting for 13.67% of the total effect）. ConclusionInternalized stigma in patients with schizophrenia patients can not only directly affect the quality of life， but also indirectly affect the quality of life of patients through either separate or chained mediation of self-esteem and the severity of negative symptoms. ［Funded by Hubei Provincial Undergraduate Innovation and Entrepreneurship Project （number， S202410519027）］