Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective:To explore the CT and MRI features of Rosai-Dorfman disease (RDD) in nasal cavity and paranasal sinus.Methods:The study was a cross-sectional study. From July 2007 to August 2023, the imaging findings of 23 patients with pathologically confirmed sinonasal RDD were retrospectively analyzed in the Eye & ENT Hospital of Fudan University. Among 23 patients, there were nine males and 14 females with 44±16 years old. Imaging features including tumor location, the extent, density, signal, enhancement pattern of tumors, bone change, abnormal lesions in peripheral lymph nodes and other regions were recorded. The apparent diffusion coefficient (ADC) value of lesions in patients performed diffusion weighted imaging (DWI) were measured.Results:For the 23 cases, totally 20 patients showed bilateral sinonasal involvement and three patients had unilateral lesions. Totally nine patients had lesions confined to the nasal cavity and paranasal sinuses, and 14 patients had lesions with extrasinonasal invasion, including orbit (6 cases), nasolacrimal duct (9 cases), anterior skull base (3 cases), nasal dorsum subcutaneous tissue (2 cases) and hard palate (1 case). Soft tissue lesions on the posterior wall of the subglottic trachea were found in 2 cases and intracranial lesions were found in 1 case. Totally 10 patients were accompanied by lymph nodes enlargement. The lesions showed isodense on all 20 non-contrast enhanced CT images, and mild enhancement in three cases, moderate enhancement in seven cases and significant enhancement in seven cases on CT enhancement images. Bone changes were found in 19 of 20 patients on CT, showing mild bone destruction in five cases and bone destruction with hyperplasia in 14 cases. The lesions showed isointense on T 1WI in all 14 cases. The lesions were graded as isointense in nine cases, hypointense in four cases and hyperintense in one case on T 2WI. The lesions displayed moderate to obvious homogeneous enhancement on enhanced MRI. The lesions showed significant diffusion limitation and ADC value was (0.66±0.08)×10 -3 mm 2/s in 11 cases on DWI. Conclusions:The CT and MRI imaging characteristics of sinonasal RDD are diffuse masses on both sides of nasal cavity and paranasal sinuses, accompanied by bone hyperplasia. The lesions show isointense or hypointense on T 2WI, and may involve adjacent tissues and may be accompanied by lymph nodes enlargement in the retropharyngeal and neck.

Objective:To explore the CT and MRI features of Rosai-Dorfman disease (RDD) in nasal cavity and paranasal sinus.Methods:The study was a cross-sectional study. From July 2007 to August 2023, the imaging findings of 23 patients with pathologically confirmed sinonasal RDD were retrospectively analyzed in the Eye & ENT Hospital of Fudan University. Among 23 patients, there were nine males and 14 females with 44±16 years old. Imaging features including tumor location, the extent, density, signal, enhancement pattern of tumors, bone change, abnormal lesions in peripheral lymph nodes and other regions were recorded. The apparent diffusion coefficient (ADC) value of lesions in patients performed diffusion weighted imaging (DWI) were measured.Results:For the 23 cases, totally 20 patients showed bilateral sinonasal involvement and three patients had unilateral lesions. Totally nine patients had lesions confined to the nasal cavity and paranasal sinuses, and 14 patients had lesions with extrasinonasal invasion, including orbit (6 cases), nasolacrimal duct (9 cases), anterior skull base (3 cases), nasal dorsum subcutaneous tissue (2 cases) and hard palate (1 case). Soft tissue lesions on the posterior wall of the subglottic trachea were found in 2 cases and intracranial lesions were found in 1 case. Totally 10 patients were accompanied by lymph nodes enlargement. The lesions showed isodense on all 20 non-contrast enhanced CT images, and mild enhancement in three cases, moderate enhancement in seven cases and significant enhancement in seven cases on CT enhancement images. Bone changes were found in 19 of 20 patients on CT, showing mild bone destruction in five cases and bone destruction with hyperplasia in 14 cases. The lesions showed isointense on T 1WI in all 14 cases. The lesions were graded as isointense in nine cases, hypointense in four cases and hyperintense in one case on T 2WI. The lesions displayed moderate to obvious homogeneous enhancement on enhanced MRI. The lesions showed significant diffusion limitation and ADC value was (0.66±0.08)×10 -3 mm 2/s in 11 cases on DWI. Conclusions:The CT and MRI imaging characteristics of sinonasal RDD are diffuse masses on both sides of nasal cavity and paranasal sinuses, accompanied by bone hyperplasia. The lesions show isointense or hypointense on T 2WI, and may involve adjacent tissues and may be accompanied by lymph nodes enlargement in the retropharyngeal and neck.

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Background and purpose:In recent years, the studies indicated that postoperatively induced myeloid-derived suppressor cells (MDSCs) were qualified with potent proangiogenic and tumor-promotive ability. Bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of MDSCs. However, the relationship of MDSCs and tumor metastasis during perioperative period, and whether BMSCs could prevent tumor metastasis through inhibiting MDSCs are not clariifed. This study aimed to investigate the change of MDSCs during perioperative period and its correlation with tumor metastasis after surgery, and the inlfuence of BMSCs on the induction of MDSCs and the development of postoperative tumor metastasis.Methods:LLC cells were injected intravenously into C57BL/6 mice. Two hours later, these mice were divided into 4 groups: controls (C group); mice given anesthesia (A group); mice given anesthesia and laparotomy (AL group) and mice given anesthesia, laparotomy, and hepatic lobectomy (ALH group). The AL mice were divided into 2 groups after surgical operation: the AL mice without treatment (ALL group) and the AL mice treated with syngeneic BMSCs (ALB group). The percentage of Gr-1+CD11b+ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. The numbers of metastases on the lung surface were counted on the 14th day after LLC infusion. BMSCs were also co-culturedin vitro with myeloid cells in order to illustrate the effects of BMSCs on the generation of MDSCs.Results:The numbers of lung metastases in AL and ALH group signiifcantly increased as compared with C and A group (P<0.01). The number of lung metastases in ALH group signiifcantly increased as compared with AL group (P<0.05). The percentage of Gr-1+CD11b+ cells in PBMCs during postoperative period signiifcantly increased in AL and ALH group as compared with C and A group, and the percentage of Gr-1+CD11b+ cells in ALH group also signiifcantly increased as compared with AL group. The numbers of lung metastases in AL and ALB group were (38.00±9.57) and (6.54±1.49), the difference was statistically signiifcant (P<0.01) on day 14 after LLC infusion. Meanwhile, the percentage of Gr-1+CD11b+ cells in ALB group signiifcantly decreased as compared with AL1 group. This study also demonstrated that BMSCs inhibited the induction and proliferation of MDSCs from myeloid cells in vitro.Conclusion:Surgery stress induces MDSCs and promotes tumor metastasis. Syngeneic BMSCs could inhibit the generation of MDSCs and further suppress tumor metastasis after surgery.

Objective To explore pathogen spectrum constitution of acute diarrhea in outpatient and emergency of Zhejiang Province, and provide basis for treatment, prevention and control of the disease. Methods During January 2009 to December 2014, we selected seven sentinel hospitals in different regions of Zhejiang, monitored and researched on pathogen spectrum in patients with acute diarrhea from outpatient and emergency. We recorded patients' personal basic information, the main symptoms and signs, and collected stool samples (5 g). Eight kinds of bacteria (Vibrio cholerae, Shigella spp., Salmonella spp., Diarrheagenic E. coli, Vibrio parahaemolyticus, Aeromonas hydrophila, Yersinia enterocolitica and Plesiomonas shigelloides) and five kinds of viruses (Rotavirus, Norovirus, Sappovirus, Astrovirus and Adenovirus) were detected. Chi-square test and Fisher's exact probability method were used to compare different characteristics of patients with single bacterial infection, single virus infection and multiple infection (bacteria-bacteria, bacteria-viruses, virus-virus). Results During 2009 to 2014, 9 364 fecal
samples from acute diarrhea patients were collected and tested, among which 3 500 cases were tested positive, with total positive rate of 37.38%. Positive rates of bacteria and viruses were 13.14%(1 230 cases) and 20.75%(1 943 cases), respectively. Mixed infection positive rate of multiple pathogens was 3.49%(327 cases). Positive rate of Vibrio parahaemolyticus (5.96%, 558 cases) was the highest among bacterial pathogens, followed by pathogenic Escherichia coli (3.86%, 361 cases). Viruses were mainly Norovirus (10.73%, 1 005 cases) and rotavirus (8.35%, 782 cases). A big difference existed in diarrheogenic pathogen spectrum between patients less than 15 years old and patients equal or older than 15 years old. Pathogens for patients less than 15 years old were mainly virus, with the positive rate of 32.69%(1 014 cases). However, the positive rate of bacteria was 16.86% (1 056 cases) in patients equal or older than 15 years old. Single bacterial infection was highest in age group of 25-34 years old (18.62%, 302 cases) , single virus infection was highest in age group of 1-4 years old (41.12%, 435 cases) , and mixed infections of multiple pathogens were mainly existed in age group of 1-4 years old (7.37%, 78 cases) . Pathogen positive rate were increasing year by year. Pathogen positive rate of patients with acute diarrhea has obvious seasonality, with single bacterial infection being highest during July to September and single virus infection being highest during December to March. Pathogen spectrum of outpatient and emergency patients with acute diarrhea in Zhejiang Province changed a little from 2009 to 2014, mainly rotavirus (22.34% (782/3 500)), norovirus (28.71%(1 005/3 500)), vibrio parahaemolyticus (15.92%(558/3 500)) and Escherichia coli (10.31%(361/3 500)). However, pathogen spectrums in different years owned different features. Conclusion Common pathogens in outpatient and emergency patients with acute diarrhea in Zhejiang Province were tested with significant seasonal epidemic law. The composition of pathogenic spectrum was variant in different age group. Constitutes of major pathogen spectrum in different years differed a little.

Objective To explore pathogen spectrum constitution of acute diarrhea in outpatient and emergency of Zhejiang Province, and provide basis for treatment, prevention and control of the disease. Methods During January 2009 to December 2014, we selected seven sentinel hospitals in different regions of Zhejiang, monitored and researched on pathogen spectrum in patients with acute diarrhea from outpatient and emergency. We recorded patients' personal basic information, the main symptoms and signs, and collected stool samples (5 g). Eight kinds of bacteria (Vibrio cholerae, Shigella spp., Salmonella spp., Diarrheagenic E. coli, Vibrio parahaemolyticus, Aeromonas hydrophila, Yersinia enterocolitica and Plesiomonas shigelloides) and five kinds of viruses (Rotavirus, Norovirus, Sappovirus, Astrovirus and Adenovirus) were detected. Chi-square test and Fisher's exact probability method were used to compare different characteristics of patients with single bacterial infection, single virus infection and multiple infection (bacteria-bacteria, bacteria-viruses, virus-virus). Results During 2009 to 2014, 9 364 fecal
samples from acute diarrhea patients were collected and tested, among which 3 500 cases were tested positive, with total positive rate of 37.38%. Positive rates of bacteria and viruses were 13.14%(1 230 cases) and 20.75%(1 943 cases), respectively. Mixed infection positive rate of multiple pathogens was 3.49%(327 cases). Positive rate of Vibrio parahaemolyticus (5.96%, 558 cases) was the highest among bacterial pathogens, followed by pathogenic Escherichia coli (3.86%, 361 cases). Viruses were mainly Norovirus (10.73%, 1 005 cases) and rotavirus (8.35%, 782 cases). A big difference existed in diarrheogenic pathogen spectrum between patients less than 15 years old and patients equal or older than 15 years old. Pathogens for patients less than 15 years old were mainly virus, with the positive rate of 32.69%(1 014 cases). However, the positive rate of bacteria was 16.86% (1 056 cases) in patients equal or older than 15 years old. Single bacterial infection was highest in age group of 25-34 years old (18.62%, 302 cases) , single virus infection was highest in age group of 1-4 years old (41.12%, 435 cases) , and mixed infections of multiple pathogens were mainly existed in age group of 1-4 years old (7.37%, 78 cases) . Pathogen positive rate were increasing year by year. Pathogen positive rate of patients with acute diarrhea has obvious seasonality, with single bacterial infection being highest during July to September and single virus infection being highest during December to March. Pathogen spectrum of outpatient and emergency patients with acute diarrhea in Zhejiang Province changed a little from 2009 to 2014, mainly rotavirus (22.34% (782/3 500)), norovirus (28.71%(1 005/3 500)), vibrio parahaemolyticus (15.92%(558/3 500)) and Escherichia coli (10.31%(361/3 500)). However, pathogen spectrums in different years owned different features. Conclusion Common pathogens in outpatient and emergency patients with acute diarrhea in Zhejiang Province were tested with significant seasonal epidemic law. The composition of pathogenic spectrum was variant in different age group. Constitutes of major pathogen spectrum in different years differed a little.

Bats are important reservoir animals and more than 60 viruses have been identified in bats with many of them highly pathogenic to human. In order to understand the natural background, genetic diversity of bat viruses in China and discover potential viral pathogens, Solexa sequencing based viral metagenomics focusing on bats tissues was established and to analyze the virome of bats collected from Jilin, Yunnan and Hunan province. By Solexa sequencing, 116 442 324 useful reads were obtained and assembled into 4 872 contigs, of which 8.2% (4 002/4 4872) were annotated to 36 viral families, including 19 vertebrate virus families, 6 plant virus families, 4 insect virus families and 4 phages. Further contigs analyses showed that some adenovirus, bocavirus, picobirnavirus, parvovirus contigs sequences were similar with known viruses. However, part of them shared limited identities to these viruses implying the discovery of new viruses. Moreover, PCR validation of adenovirus and bocavirus confirmed the results obtained by viral metagenomics. This study aimed to understand bat virome in China by viral metagenomics and could be helpful to establish effective surveillance on wildlife-associate zoonoses.
Adenoviridae ; genetics ; isolation & purification ; Animals ; Bunyaviridae ; genetics ; isolation & purification ; China ; Chiroptera ; virology ; Genome, Viral ; genetics ; Metagenome ; genetics ; Metagenomics ; methods ; Picornaviridae ; genetics ; isolation & purification

Objective To establish a method of cultivation of dendritic cells (DC) from mouse bone marrow in vitro and identify their phenotype and function. Methods Under aseptic condition, bone marrow cells were extracted from the tibia and femur bones of BALB/c mice. Bone marrow cells were cultured with recombinant mouse granulocyte-macrophage colony-stimulating factor ( rmGM-CSF) in vitro. The expansion and morphological changes of DC were observed with light inverted microscope. Phenotype was identified with flow cytometry and biological function was studied with antigen phagocytosis test. Results A large number of immature and mature DC with typical dendritic morphological characteristics could be generated from murine bone marrow. Immature DC, which had high expression in CD11c and low expression in CD40, MHC-II and CD86, could phagocytize antigen. Mature DC, which could be induced from immature DC by lipopolysaccharides, had high expression in CD11c, CD40, CD86 and MHC-II molecules. Conclusion Immature and mature DC can be generated from mouse bone marrow cells through cytokine induction in vitro and be used for further study associated with DC.