BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Yttrium-90 microsphere selective internal radiation therapy (SIRT), also known as transarterial radioembolization, has become one of the pivotal treatments for liver cancer, particularly for selected advantageous patient groups. This review summarizes the characteristics of different patients with liver cancer that could obtain maximum benefit from SIRT and discusses key factors affecting efficacy and safety, including tumor characteristics, liver function, patient performance status, and treatment intent. In evaluating appropriate candidates, mapping serves as a crucial simulation procedure to assess tumor vascular anatomy, predict lung shunting, and guide catheter positioning and dose planning. This procedure substantially enhances therapeutic precision while minimizing the risk of nontarget radiation-related adverse events, such as radiation-induced pneumonitis and gastrointestinal toxicity. Several studies have suggested that SIRT is not only suitable for patients with early or limited hepatocellular carcinoma but can also be used as a bridging therapy for liver transplantation and conversion therapy for unresectable liver cancers. In combination with systemic treatments, SIRT has demonstrated survival benefits in patients with unresectable liver cancer. This review also highlights the importance of further optimizing patient screening through personalized dosimetry and mapping to ensure the precision and safety of treatment. A thorough review of relevant literature and clinical practice offers clinicians comprehensive suggestions on patient screening and clarifies the promise of SIRT in the liver cancer population.

Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

OBJECTIVES: To investigate the protective mechanism of quercetin, the core component of Zuo Gui Wan, against Alzheimer's disease through the PI3K/AKT signaling pathway, based on network pharmacology, molecular docking, and cell experi-ments. METHODS: The active components of Zuo Gui Wan were identified by searching TCMSP, PubChem, Swiss Target Prediction, and BATMAN-TCM databases, and their potential targets were predicted. The target information was standardized using Uniprot, and Alzheimer's disease-related target genes were obtained from Drugbank, GeneCards, and OMIM. The intersection of these datasets was used to identify the potential targets of Zuo Gui Wan for treating Alzheimer's disease. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The protein-protein interaction (PPI) network of potential targets was visualized using Cytoscape 3.10.1 software and the STRING database. The key active compounds and core potential targets for treating Alzheimer's disease with Zuo Gui Wan were identified through calculation. Based on the enrichment analysis results and literature, quercetin and the PI3K/AKT pathway were selected for verification. Molecular docking and binding ability prediction between quercetin and the core target AKT were performed using CB-Dock2, and visualization was conducted with AutoDock and PyMOL software. Finally, Aβ_1-42-induced HT-22 mouse hippocampal neuronal cells were used to construct an Alzheimer's disease cell model. Quercetin, the PI3K inhibitor LY294002, and the activator EGF were used as interventions. The groups were divided as follows: Control, Aβ_1-42, Aβ_1-42+Quercetin 2.5 μM, Aβ_1-42+Quercetin 5 μM, Aβ_1-42+Quercetin 10 μM, Aβ_1-42+EGF, and the PI3K/AKT modulation group: Control, LY294002, LY294002+Quercetin 10 μM, LY294002+EGF. CCK-8 assays were performed to detect cell viability, while JC-1, Calcein AM-PI, and Hoechst staining were used to assess cell apoptosis. Western blotting was employed to detect the expression of relevant target proteins. RESULTS: Network pharmacology and cell experiments collectively demonstrate that the key active ingredient of Zuo Gui Wan, quercetin, targets core proteins such as AKT1 and GSK3β through a network-based approach, significantly enriching the PI3K/AKT pathway. Molecular docking results indicate that quercetin has a strong binding affinity with AKT. Experimental validation in the Aβ_1-42 oligomer-induced HT-22 model reveals that quercetin significantly activates the PI3K/AKT signaling pathway, which is inhibited by Aβ_1-42 oligomers, as well as Bcl-2 protein expression. It also suppresses the expression of Cleaved Caspase 3/Caspase 3, BAX, and Cytochrome C proteins. JC-1, Hoechst 33342, and Calcein AM-PI staining results further show that quercetin can significantly alleviate apoptosis induced by Aβ_1-42 oligomers in HT-22 cells. Treatment with the PI3K inhibitor LY294002 in HT-22 cells leads to reduced cell viability and decreased expression of p-AKT/AKT and Bcl-2 proteins, while increasing the expression of Cleaved Caspase 3/Caspase 3, BAX, and Cytochrome C proteins. Additionally, apoptosis levels increase as observed in JC-1, Hoechst 33342, and Calcein AM-PI staining, all of which can be reversed by quercetin and the PI3K agonist EGF. CONCLUSIONS Quercetin, the key active ingredient of Zuo Gui Wan, exerts its protective effects against Alzheimer's disease by regulating the PI3K/AKT signaling pathway, inhibiting neuronal cell damage and apoptosis.

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Objective : To investigate the correlation between the pan-immune inflammation value (PIV) and clini- cal and pathological features of primary IgA nephropathy (IgAN) ，and to evaluate the clinical significance of PIV in primary IgAN． Methods: 200 patients with primary IgAN diagnosed by renal biopsy were selected as the re- search subjects．General information，laboratory indicators，pathologic features of renal biopsy，and calculations of platelet to lymphocyte count ratio(PLR) ，neutrophil to lymphocyte count ratio(NLR) ，PIV，and other relevant in- dices about patients were collected．According to the median PIV，subjects were divided into low PIV group (PIV ≤194. 81) and high PIV group ( PIV ＞194. 81) ，and the clinical and pathological data of the two groups were compared and analyzed．Using Spearman rank correlation analysis and logistic regression analysis，the relationship between PIV and primary IgAN in terms of clinical and pathological aspects was explored． Results: There were sta- tistical significance in age，gender，height，hyperuricemia，hemoglobin，absolute neutrophil count (ANC) ，absolute monocytes count，platelet，PLR , NLR , serum uric acid，immunoglobulin G(IgG) ，immunoglobulin A(IgA) / com- plement 3 ( C3) ，and fusion degree of the podocyte foot between the two sets (P＜0. 05) ．The result of correlation analysis indicated that PIV was positively correlated with ANC，platelet，absolute monocytes count，PLR , NLR , serum creatinine，C3，serum uric acid，and fusion degree of the podocyte foot，but negatively correlated with IgG， IgA/ C3，IgA/ C4．The degree of podocyte foot process fusion was positively correlated with PIV，ANC，total choles- terol，and 24-hour urinary protein to creatinine ratio，and negatively correlated with albumin(ALB) ，IgG，IgA，and IgA/ C3．Logistic regression analysis further indicated that ALB was an independent protective factor for the occur- rence of podocyte foot process fusion in primary IgAN，and PIV was an independent risk factor for the occurrence of podocyte foot process fusion in primary IgAN． Conclusion PIV is closely related to the clinical symptoms and pathological lesions of primary IgAN．ALB is an independent protective factor for the occurrence of podocyte foot process fusion in primary IgAN，and PIV is an independent risk factor for the occurrence of podocyte foot process fu- sion in primary IgAN，which can be used as an auxiliary indicator of clinical and pathological results，providing valuable information for risk assessment and treatment plan formulation of primary IgAN．

Objective To investigate the risk factors for cardiovascular disease(CVD)in patients with rheumatoid arthritis(RA).Methods Clinical data of 225 patients with RA admitted to the Second Affiliated Hospital of Zhengzhou University from January 2023 to September 2024 were collected,and the patients were divided into CVD group(n=50)and non-CVD group(n=175)according to whether they were complicated by CVD.Univariate and multivariate Logistic regression was used to analyze the risk factors of CVD in RA patients.Results Univariate Logistic regression analysis showed that age,hematocrit,red cell volume distribution width(RDW),erythrocyte sedimentation rate,neutrophil to high density lipoprotein ratio(NHR)and platelet to lymphocyte ratio(PLR)were all influencing factors for CVD in RA patients(P＜0.05).Multivariate Logistic regression analysis showed that age,RDW,NHR and PLR were all risk factors for CVD in RA patients(P＜0.05).The results of receiver operating characteristic curve analysis showed that the area under the curve(AUC)of age,RDW,NHR and PLR diagnosed CVD in RA patients were 0.844,0.797,0.572 and 0.713,respectively.The combined diagnosis AUC of four indexes was 0.898.Conclusion The risk of CVD in RA patients is influenced by many factors,and the combination of age,RDW,NHR,and PLR can improve early diagnosis of CVD in RA patients.

To analyze the transmission characteristics of newly reported HIV-infected students aged ≥18 years in Nanjing City from 2016 to 2022 and provide evidence for AIDS publicity and intervention among young students. The pol region sequences of newly reported HIV-infected students and non-student HIV-infected individuals in Nanjing City from 2016 to 2022 were collected, and the BLAST tool was used to search the published global non-Nanjing reported HIV infection sequences in the LANL HIV database. The basic molecular transmission network and regional molecular transmission network were constructed using the HIV-TRACE in a pairwise genetic distance threshold of 1.0%. 332 sequences of infected students aged≥18 years in Nanjing City, 1 904 sequences of non-student-infected individuals in Nanjing City and 1 698 non-Nanjing-infected individuals were obtained. Among the 332 infected students, the main route of infection was homosexual (96.39%), and the subtypes were CRF01_AE (37.95%), CRF07_BC (37.65%) and CRF105_0107 (10.24%). There were 890 sequences in the regional molecular transmission network, of which 21.80% were infected students in Nanjing City, 39.89% were non-student-infected individuals in Nanjing City, and 38.31% were non-Nanjing-infected individuals. In the CRF105_0107 transmission cluster, non-student-infected individuals from Nanjing accounted for 66.95% (81/121), while in the CRF07_BC transmission cluster, non-Nanjing-infected individuals accounted for 56.66% (200/353). There were 1 644 edges connected to infected students within the regional molecular transmission network, with local transmission accounting for 64.72% and regional transmission accounting for 35.28%. Regional transmission was mainly in Guangdong Province (19.83%) and other cities in Jiangsu Province (4.50%). The HIV-1 subtypes of newly reported HIV-infected students aged≥18 years in Nanjing City are mainly CRF01_AE, CRF07_BC and CRF105_0107, with local transmission as the main transmission characteristics. There is transmission between students and non-students.