ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

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.

Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

OBJECTIVE To establish a nomogram model based on clinical and biochemical parameters in elderly patients with p16-negative nasopharyngeal carcinoma and to identify patients who may benefit from concurrent chemoradiotherapy(CCRT)combined with induction chemotherapy(IC).METHODS A total of 142 nasopharyngeal carcinoma patients who received CCRT in Huanggang Central Hospital between June 2021 and May 2024 were retrospectively included for analysis,and the patients were divided into a training set(n=99)and a validation set(n=43)in a ratio of 7:3.Before treatment,all patients underwent a complete physical examination,fiberoptic nasopharyngeal endoscopy,laboratory tests,and plasma Epstein-Barr virus deoxyribonucleic acid(EBV-DNA)level detection.The study endpoint was disease-specific survival(DSS),defined as the time from initial treatment to cancer-related death or the last follow-up date.RESULTS EBV-DNA level,T stage,N stage,albumin(ALB),and lactate dehydrogenase(LDH)were screened by COX and LASSO regression analysis to establish a nomogram model for predicting DSS in nasopharyngeal carcinoma patients.The nomogram model had good discrimination ability[C-index value:0.947(95%CI:0.905-0.990)vs.0.930(95%CI:0.862-0.998)]and accuracy in both the training set and the validation set.The nomogram model was divided into low-risk group,medium-risk group and high-risk group according to risk.There were statistical differences in DSS among the three groups in the training set and validation set(χ2=7.153,9.266,P=0.028,0.010).In the training set and validation set,only the patients in the high-risk group who received IC+CCRT had a longer DSS than those who received CCRT.CONCLUSION The nomogram model of pre-treatment EBV-DNA level,T stage,N stage,ALB,and LDH was used to distinguish high-risk elderly p16-negative nasopharyngeal carcinoma patients,suggesting that this population may be the beneficiary of IC+CCRT in clinical practice.

Medical visual question answering (MVQA) plays a crucial role in the fields of computer-aided diagnosis and telemedicine. Due to the limited size and uneven annotation quality of the MVQA datasets, most existing methods rely on additional datasets for pre-training and use discriminant formulas to predict answers from a predefined set of labels. This approach makes the model prone to overfitting in low resource domains. To cope with the above problems, we propose an image-aware generative MVQA method based on image caption prompts. Firstly, we combine a dual visual feature extractor with a progressive bilinear attention interaction module to extract multi-level image features. Secondly, we propose an image caption prompt method to guide the model to better understand the image information. Finally, the image-aware generative model is used to generate answers. Experimental results show that our proposed method outperforms existing models on the MVQA task, realizing efficient visual feature extraction, as well as flexible and accurate answer outputs with small computational costs in low-resource domains. It is of great significance for achieving personalized precision medicine, reducing medical burden, and improving medical diagnosis efficiency.
Humans ; Image Processing, Computer-Assisted/methods* ; Diagnosis, Computer-Assisted/methods* ; Algorithms ; Telemedicine

ObjectiveTo analyze the changing trend of the disease burden of acute viral hepatitis （AVH） globally and in China from 1990 to 2021， and to provide a basis for optimizing prevention and control strategies. MethodsRelated data were extracted from the Global Burden of Disease 2021 database， including incidence rate， mortality rate， and disability-adjusted life years （DALY） for AVH globally and in China from 1990 to 2021， and the patients were divided into groups according to region， age， sex， and type of hepatitis. The Joinpoint regression model was used to calculate average annual percentage change （AAPC） and its 95% confidence interval （CI）. ResultsFrom 1990 to 2021， there was a tendency of reduction in the age-standardized incidence rate， mortality rate， and DALY rate of AVH globally， with an average annual reduction of 1.02% （95%CI： -1.10% to -0.94%， P<0.001）， 3.97% （95%CI： -4.12% to -3.82%， P<0.001）， and 3.64% （95%CI： -3.84% to -3.44%， P<0.001）， respectively； in China， there was also a tendency of reduction in these indicators， with an average annual reduction of 1.63% （95%CI： -1.70% to -1.57%， P<0.001）， 9.24% （95%CI： -9.51% to -8.97%， P<0.001）， and 7.93% （95%CI： -8.15% to -7.71%， P<0.001）， respectively. In addition， China’s share of the global disease burden of AVH continued to decrease； the proportion of new cases decreased from 24% in 1990 to 15% in 2021， the proportion of deaths decreased from 19% to 4%， and the proportion of DALY decreased from 16% to 4%. From 1990 to 2021 globally， the peaks in the incidence rate， mortality， and DALY of AVH were observed in children under 5 years of age； in China， although the peak incidence rate of the disease was still observed in children under 5 years of age， there was a tendency of increase in the incidence rate of AVH among young adults aged 25 — 29 years in recent years， with the most significant increase in the cases of acute hepatitis B （accounting for 59% of the cases in this age group）， while the disease burden of mortality and DALY mainly affected the middle-aged and elderly populations. The disease burden of AVH in the male population was higher than that in the female population. As for the distribution of disease types， acute hepatitis A was the predominant type of AVH， accounting for 64% globally and 48% in China， whereas acute hepatitis B was the leading cause of mortality and DALY， accounting for 50% of deaths globally， 80% of deaths in China， 47% of DALY globally， and 69% of DALY in China. ConclusionThere is a tendency of reduction in the disease burden of AVH globally and in China from 1990 to 2021， but there is a tendency of increase in the incidence rate of AVH among young adults in China， especially acute hepatitis B. It is necessary to implement targeted prevention and control strategies.

Objective: To explore the association between various components of sleep quality and the co-occurrence of non-suicidal self-injury (NSSI) behaviors and depressive symptoms among junior high school students, so as to provide evidence for targeted prevention strategies of NSSI and depression. Methods: From May to June 2024, a total of 5 008 junior high school students from 8 schools in 2 districts/counties of Chongqing were selected through a stratified cluster sampling method. The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies Depression Scale (CES-D), and the Adolescent Non suicidal Self injury Assessment Questionnaire (ANSAQ) were used to assess sleep quality, depressive symptoms, and NSSI, respectively. Data were analyzed by using the Chi-square test, Bonferroni correction, and multivariate Logistic regression. Results: Non-NSSI group and depressive symptoms group accounted for 68.11% among junior high school students, NSSI-only group accounted for 4.71%, only depressive symptoms group accounted for 14.94%, and co-occurrence of NSSI and depressive symptoms group accounted for 12.24%. The prevalence of the co-occurrence group was higher in girls (16.39%) than in boys (7.85%) ( χ 2=84.89, P <0.01). After controlling for gender, grade, and boarding status etc., multivariate Logistic regression analysis revealed that five sleep components, including subjective sleep quality, sleep latency, sleep duration, sleep disturbances, and daytime dysfunction, were significantly and positively associated with the co-occurrence of NSSI and depressive symptoms ( OR =1.30-3.86, all P <0.05). The strength of association between these components and the co-occurrence group, in descending order, was: daytime dysfunction ( OR = 2.52), sleep disturbances ( OR =2.36), subjective sleep quality ( OR =1.76), sleep latency ( OR =1.44), and sleep duration ( OR =1.22) (all P <0.01). Conclusions The co-occurrence of NSSI and depressive symptoms is prevalent among junior high school students, with girls being more significantly affected. Sleep disturbances and daytime dysfunction may represent particularly important risk factors. Targeted and prioritized intervention strategies addressing specific sleep components should be developed and implemented to reduce the co-occurrence of NSSI and depressive symptoms in junior high school students.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.