Giant cell tumor of bone (GCTB) is a common locally aggressive junctional primary bone tumor, whose clinical treatment becomes more difficult once combined with pathological fracture. Extended curettage and en-bloc resection are common surgical procedures for treating GCTB, and drugs such as receptor activator of nuclear factor-κB ligand(RANKL) inhibitors and bisphosphonates have been successfully used. Curettage is recommended for patients with Campanaccigrade Ⅱor Campanaccigrade Ⅲ with localized soft tissue invasion only and simple fractures with intact bone structure. Resection may be considered for Campanaccigrade Ⅲ with extensive soft tissue invasion or complex fractures with incomplete bone structure. RANKL inhibitors such as denosumab may be recommended if surgery is not possible or before performing resection. This article summarizes the common treatment modalities of pathological fractures combined with giant cell tumors of extremities, including the current status of surgical and pharmacological treatments, analyzing the choice of surgical modalities in different clinical situations, in order to provide clinical inspirations for diagnosis and treatment.

Giant cell tumor of bone (GCTB) is a common locally aggressive junctional primary bone tumor, whose clinical treatment becomes more difficult once combined with pathological fracture. Extended curettage and en-bloc resection are common surgical procedures for treating GCTB, and drugs such as receptor activator of nuclear factor-κB ligand(RANKL) inhibitors and bisphosphonates have been successfully used. Curettage is recommended for patients with Campanaccigrade Ⅱor Campanaccigrade Ⅲ with localized soft tissue invasion only and simple fractures with intact bone structure. Resection may be considered for Campanaccigrade Ⅲ with extensive soft tissue invasion or complex fractures with incomplete bone structure. RANKL inhibitors such as denosumab may be recommended if surgery is not possible or before performing resection. This article summarizes the common treatment modalities of pathological fractures combined with giant cell tumors of extremities, including the current status of surgical and pharmacological treatments, analyzing the choice of surgical modalities in different clinical situations, in order to provide clinical inspirations for diagnosis and treatment.

Objective To investigate prognostic value of serum levels of cathepsin B(CTSB)and NADPH oxidase 4(NOX4)in patients with sepsis associated acute kidney injury(S-AKI).Methods A total of 306 pa-tients with sepsis treated to the hospital from June 2023 to June 2024 were selected,including 192 patients with S-AKI(S-AKI group)and 114 patients without S-AKI(non-S-AKI group).According to the prognosis of S-AKI patients,they were divided into poor prognosis group(n=127)and non-poor prognosis group(n=65).The differences of CTSB and NOX4 in different groups were compared.Pearson analysis was conducted to analyze the correlation between CTSB,NOX4 and clinical indicators.The influencing factors of poor prognosis in S-AKI patients was analyzed according to multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTSB and NOX4 on the poor prognosis of S-AKI pa-tients.Results Th e serum levels of CTSB,NOX4 and serum creatinine(SCr)in S-AKI group were signifi-cantly higher than those in non-S-AKI group(P＜0.05),while the mean arterial pressure and oxygenation in-dex were lower than those in non-S-AKI group(P＜0.05).Serum levels of CTSB and NOX4 in patients with sepsis were positively correlated with SCr(P＜0.05).Compared to non-poor prognosis group,the age,SCr,CTSB and NOX4 of patients in the poor prognosis group were higher,while the mean arterial pressure and ox-ygenation index were lower(P＜0.05).The increased mean arterial pressure and oxygenation index were pro-tective factors for poor prognosis in S-AKI patients(P＜0.05),and the increased age,SCr,CTSB and NOX4 levels were risk factors for poor prognosis in S-AKI patients(P＜0.05).ROC curve showed that the area un-der the curve(AUC)of CTSB combined with NOX4 was significantly higher than AUC of single detection of CTSB and NOX4(Z=4.066,P＜0.001,Z=3.801,P＜0.001).Conclusion The serum levels of CTSB and NOX4 in S-AKI patients are elevated,and can indirectly reflect kidney function.CTSB combined with NOX4 can significantly improve the prediction efficiency of poor prognosis in S-AKI patients,which has potential ap-plication value for clinical treatment and nursing.

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective:To explore the effects of depressive symptoms on sleep quality in adolescents with depressive disorder, and the mediating roles of cognitive fusion and sleep belief.Methods:A sample of 210 adolescents with first episode depressive disorder aged 12-18 years were recruited to complete 17-item Hamilton depression scale (HAMD-17), Pittsburgh sleep quality index (PSQI), cognitive fusion questionnaire (CFQ), and dysfunctional beliefs and attitudes about sleep scale (DBAS-16) from November 2021 to July 2022. SPSS 26.0 software was used to perform descriptive analysis and correlation analysis. The mediating effect was tested by Bootstrap analysis using PROCESS V 3.4 Macro program.Results:The incidence of low sleep quality in adolescents with depressive disorder was 69.0%(145/210). HAMD-17 score was (22.4±7.9), PSQI score was (9.7±3.7), CFQ score was (51.6±7.8), DBAS-16 score was (43.5±8.4).PSQI was positively correlated with the scores of HAMD-17 and CFQ( r=0.613, 0.463, both P<0.001).HAMD-17 was positively correlated with CFQ score ( r=0.488, P<0.001).DBAS-16 was negatively correlated with scores of PSQI, HAMD-17 and CFQ( r=-0.326, -0.284, -0.354, all P<0.001). The direct effect of depression on sleep quality was 0.230(95% CI=0.169-0.293). The indirect effect of depression on sleep quality through two pathways, the separate mediating effect value of cognitive fusion was 0.041 (95% CI=0.011-0.074), and the chain mediating effect value of cognitive fusion and sleep beliefs was 0.008(95% CI=0.001-0.020). Conclusion:Depressive symptoms can directly affect sleep quality of depressive disorder adolescents and indirectly through cognitive fusion and sleep beliefs.

Excellent lead compounds have a profound influence on drug development and can improve the success rate of product launch. It is expensive and time-consuming to discover lead compounds by traditional methods, yet artificial intelligence (AI) can discover good lead compounds efficiently.This article systematically summarizes the research progress of obtaining lead compounds through the screening and generation models of AI, classifies different models according to the type of information input, focuses on drug repurposing by screening model and multi-objective drug design by generation model, and discusses the development prospect of AI in the research field of lead compounds, aiming to provide new research ideas for the application of AI in lead compounds.

Objective:To investigate the application value of aortic dissection detection risk score (ADD-RS) combined with D-dimer (DD) in the early diagnosis of acute aortic dissection (AAD).Methods:The clinical data of 70 patients with suspected aortic dissection detection admitted to The Second Hospital of Jiaxing from August 2019 to April 2020 were collected. All patients were scored using the ADD-RS, and grouped according to the scoring results. The sensitivity and specificity of ADD-RS plus DD in the early diagnosis of AAD were calculated. The areas under the receiver operating characteristic (ROC) curves that were plotted for drADD-RS plus DD versus DD alone to screen AAD were compared to evaluate efficacy. Results:CT angiography results showed that among 70 patients with suspected AAD, 29 patients had AAD and 41 patients had no AAD. A total of 21 patients were scored 0, 41 patients were scored > 1, and 8 patients were scored > 0. ADD-RS > 0 had an overall sensitivity of 79.31% and a specificity of 36.59% for AAD diagnosis. DD test results had an overall sensitivity of 86.20% and a specificity of 36.50% for AAD diagnosis. The area under the ROC curve of ADD-RS = 0 plus DD-negative result and the area under the ROC curve of DD-negative result alone in ruling out AAD were 0.885 with 95% CI (0.786-0.949) and 0.787 with 95% CI (0.673-0.876), respectively. The difference between the two groups was statistically significant ( P = 0.024). Conclusion:Compared with DD-negative result alone, the ADD-RS = 0 plus DD-negative result strategy offers greater specificity to rule out AAD. The combined strategy has a greater efficacy in ruling out AAD. However, a multi-center study involving a large sample is required for in-depth evaluation.

Heme/metabolism* ; Cryoelectron Microscopy ; Membrane Transport Proteins ; Escherichia coli Proteins/metabolism*