Aim To investigate the effect of EGB761 on cognitive impairment in mice following ischemic stroke and its underlying mechanism.Methods Sev-enty-two mice were randomly divided into four groups(n=18 each):sham group,model group,low-dose EGB761 treatment group,and high-dose EGB761 treat-ment group.The middle cerebral artery occlusion/reperfusion(MCAO/R)mouse model was established using the thread occlusion method.The low-and high-dose groups received 50 mg·kg-1 and 150 mg·kg-1 of EGB761 respectively,once daily for 28 days after MCAO/R.Cerebral infarction volume was measured u-sing TTC staining.Neurological function was evaluated using the modified neurological function score(mNSS).The learning and cognitive function of mice was assessed by the water maze test.Neuronal apopto-sis was detected through NeuN and TUNEL co-stai-ning.Iba1 immunofluorescence staining was used to e-valuate microglia activation.The protein expression levels of TLR4,p-IKKα and NF-κB were detected by Western blot.Results Compared with the model group,both low-dose and high-dose EGB761 groups exhibited a significant reduction in cerebral infarction volume(P＜0.01),improvement in neurological func-tion as well as learning and cognitive function(P＜0.01),a significant decrease in apoptotic neurons percentage(P＜0.01),along with activated microglia(P＜0.01).Furthermore,expressions of TLR4,p-IKKα and NF-κB were significantly reduced(P＜0.05).Notably,the high-dose treatment demon-strated more pronounced effects than the low-dose treatment did.Conclusion EGB761 can ameliorate neurological and cognitive dysfunction in MACO/R mice by reducing neuronal apoptosis while inhibiting the TLR4/NF-κB pathway to mitigate excessive activa-tion of microglia.

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. Materials and Methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2′-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Conclusions Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Humans ; Female ; Deep Learning ; Ovarian Neoplasms/genetics* ; Carcinoma, Ovarian Epithelial/genetics* ; Neural Networks, Computer ; RNA

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To describe gastric cancer incidence in Suzhou cohort, explore the environmental risk factors of gastric cancer in Suzhou, and provide appropriate suggestions for gastric cancer prevention and control. Methods: The participants were from the Suzhou cohort of China Kadoorie Biobank. Baseline survey was conducted from 2004 to 2008, followed by long-term follow-up until December 31, 2013. After the exclusion of those who had been previously diagnosed with peptic ulcer and malignant tumor reported at baseline survey and gastric cancer within six months after enrollment, a total of 50,136 participants were included. Cox proportional risk models were used to identify risk factors of gastric cancer and their hazard ratios in Suzhou. The effect modifications of gender on the association between risk factors and gastric cancer were analyzed. Results: In the follow-up of 7.19 years (median), 374 gastric cancers cases occurred. The standardized incidence was 94.57 per 100 000 person-years. Multivariate Cox proportional risk model analysis found that age (10 years old as a age group, HR=2.20, 95%CI: 1.92-2.53, P<0.001), current smoking (HR=1.84, 95%CI: 1.10-3.07 P=0.020), consumption of preserved vegetables weekly (HR=2.28, 95%CI: 1.28-4.07, P=0.005) and daily (HR=2.05, 95%CI: 1.16-3.61, P=0.013) were risk factors for gastric cancer. Female (HR=0.44, 95%CI: 0.25-0.76, P=0.003) and refrigerator use (10 years as a limit, HR=0.85, 95%CI: 0.74-0.97, P=0.016) were protective factors for gastric cancer. Further analysis showed that there was heterogeneity between males and females in the association between refrigerator use years and the incidence of gastric cancer (P=0.009), and there was an interaction effect between gender and refrigerator use on the incidence of gastric cancer (P=0.010). Conclusions: The incidence of gastric cancer in Suzhou cohort was high. The risk factors of gastric cancer varied. There was a synergistic interaction effect between gender and refrigerator use years on the incidence of gastric cancer.
Child ; Cohort Studies ; Female ; Humans ; Incidence ; Male ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Stomach Neoplasms/epidemiology*

Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.
Adult ; Aged ; Augmented Reality ; Hepatectomy/methods* ; Humans ; Imaging, Three-Dimensional ; Laparoscopy/methods* ; Liver Neoplasms/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Technology

Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee. In vivo and in vitro results indicate that rhein specific binding proteins are mainly involved in amino acid anabolism, especially the arginine anabolic signaling pathway. Rhein inhibited the proliferation and migration of HCT116 cell in a concentration-dependent manner. Treated with rhein for 24 h significantly enhanced the expression of BAX and ASS1 in HCT116 cells, as well as the level of nitric oxide (NO) metabolism. In a mouse model of colorectal cancer, rhein significantly alleviated AOM/DSS induced weight loss and reduced fecal occult blood score. Meanwhile, rhein enhanced BAX and ASS1 expression in colon tumor tissue, as well as increased arginine and NO in serum. IHC and HE stain indicated that rhein alleviated Ki67 expression and macrophage infiltration in the colonic tissue of mice with AOM/DSS and delayed tumor formation. In conclusion, rhein can exert antitumor activity by regulating arginine and NO metabolism through ASS1.

OBJECTIVE: To investigate the feasibility of using thyroid ^99mTcO₄^- imaging ROI ratio instead of 24 h radioactive iodine uptake (RAIU) for estimating ¹³¹I dose in individualized treatment of hyperthyroidism. METHODS: We retrospectively analyzed the clinical data of 132 patients receiving ¹³¹I treatment in our department between January and June, 2019. According to their 3 h/24 h RAIU peak ratio, the patients were divided into peak forward (≥80%) group and no peak forward (< 80%) group. In the former group, the therapeutic ¹³¹I dose was calculated based the Marinelli formula (¹³¹I dose=thyroid mass×planned amount/24 h RAIU), and in the latter group, the correlation between the ROI ratio and the 24 h RAIU was analyzed, and the ¹³¹I dose was calculated using a modified Marinelli formula where 24 h RAIU was replaced by a converted ROI ratio. The two groups of patients were compared for antithyroid drug type and discontinuation time, thyroid hormones and related antibodies, thyroid area, thyroid mass and ¹³¹I dose. All the patients were and followed up for one year to analyze the treatment efficacy. The ROI ratios after the treatment were analyzed in the two groups using ROC curves. RESULTS: There was a significant positive correlation between the ROI ratio and 24 h RAUI in the no peak forward group (Y=58.13 + 0.2X, R²=0.118, P < 0.05), and the formula for calculating ¹³¹I dose was converted into: ¹³¹I dose=thyroid mass× planned amount/(58.13+0.2×ROI ratio)%. Before the treatment, therapeutic ¹³¹I dose, thyroid hormone levels, TRAb, 3 h and 24 h RAIU, thyroid area, thyroid mass, and ROI ratio all differed significantly between the two groups (P < 0.05). At 3 months after treatment, thyroid hormone levels, TRAb, TPOAb, thyroid area, thyroid mass, ROI ratio, response rate, hypothyroidism rate, cure rate, remission rate, and nonresponse rate were similar between two groups (P>0.05). At the 1-year follow-up, the composition ratios of hyperthyroidism, hypothyroidism and cured cases remained similar between two groups (P>0.05). ROC curve analysis showed that at 3 months after treatment, the optimal cutoff values of ROI ratio for predicting hyperthyroid recurrence and hypothyroidism were 15.79 and 6.33, respectively. CONCLUSION Thyroid ^99mTcO₄^- imaging ROI ratio can be used for calculating ¹³¹I dose in individualized treatment of hyperthyroidism and for prognostic evaluation of the patients.
Humans ; Iodine Radioisotopes/therapeutic use* ; Retrospective Studies ; Thyroid Neoplasms ; Hypothyroidism

Aim To investigate the slope ratio method for the determination of anticoagulant activity of leeches. Methods Three batches of leeches, four groups of Japanese medical vermiculite yinpian and fifteen groups of leech preparations were chosen, with contrast medicinal leeches herbs and Philippine cattle leech contrast medicinal materials, and different concentrations of leaching solutions were prepared in parallel. APTT value was determined after anticoagulant activity was determined by slope ratio method for the joint validation of laboratory, intermediate precision and accuracy between the linear range. Results The slope ratio method was accurate and accurate in the determination of anticoagulant activity of leeches, with linearity between 64% and 156% relative titer level. Conclusion Slope ratio method can be used to determine the anticoagulant activity of leeches.