OBJECTIVE To investigate the protective effect of paeoniflorin(PF) on cardiac dysfunction and myocardial cell injury induced by cisplatin(CDDP) in rats. METHODS SD male rats were randomly divided into control group, CPPD group, and CDDP PF+low-dose, high-dose group. PowerLab multifunctional recorder was used to detect the related indexes of cardiac function: the changes of left ventricular peak pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and left ventricular pressure change rate(±dp/dt). Serum levels of inflammatory factors TNF-α, IL-1β and IL-6 were measured in each group. Myocardial tissue was stained to observe the changes of tissue structure. H9c2 cardiomyocytes were divided into control group, CDDP group, PF group and CDDP+PF group. The activity of H9c2 cardiomyocytes was measured by CCK-8. The apoptosis of cardiomyocytes in each group was detected by flow cytometry. The expressions of MAPK signaling pathway related proteins p38, ERK, JNK and their phosphorylated proteins and apoptosis-related proteins Bax, Bcl-2, Casp3, Cl-casp3 were detected in cardiomyocytes by Western blotting. RESULTS Compared with the control group, LVSP and ±dp/dt decreased, LVEDP increased in rats of CDDP group(P<0.01). Compared with CDDP group, both CDDP+low-dose and high-dose PF pretreatment increased LVSP and ±dp/dt value(P<0.05 or P<0.01), decreased LVEDP(P<0.01), and could decrease the serum inflammatory factor TNF-α, IL-1β and IL-6(P<0.01). Cell level results showed that compared with control group, in CDDP group, the cell activity decreased, the apoptosis-related protein Bax, Cl-casp3 increased(P<0.01), expression of anti-apoptotic protein Bcl-2 decreased(P<0.01), and the expression of p38 and ERK phosphorylation also increased(P<0.01). Compared with CDDP group, PF could restore cell activit, down-regulate apoptosis-related protein Bax, Cl-casp3(P<0.05 or P<0.01), and increase anti-apoptotic protein Bcl-2 expression(P<0.01), inhibit MAPK pathway p38 and ERK phosphorylation expression(P<0.01). CONCLUSION PF can restore cardiac dysfunction and myocardial cell injury induced by cisplatin in rats, which may be related to inhibiting inflammation and apoptosis by regulating ERK/p38 MAPK signal expression.

Objective To investigate the effects of zalcitabine(ddC),a mitochondrial DNA polymerase γ(POLG)inhibitor,on the migration,invasion,and to preliminarily explore mitochondrial biogenesis of human tri-ple-negative breast cancer MDA-MB-231 cells.Methods The effect of ddC on cell viability was detected using the MTT assay.The migration and invasion abilities of the cells were evaluated using the cell scratch and Transwell in-vasion assays.Cell apoptosis was determined using flow cytometry and a V-FITC/PI cell apoptosis detection kit.The protein expression of POLG,NADH dehydrogenase subunit Ⅰ(NADH1),NADH dehydrogenase subunit Ⅱ(NADH2),ATP synthase subunit 6(ATPase6),cytochrome c oxidase subunit Ⅰ(COX-1)and cytochrome c ox-idase subunit Ⅲ(COX-3)were determined using Western blot.The POLG mRNA level and mtDNA copy number were determined using qPCR.The mitochondrial content and ATP levels were determined using MitoTracker Green fluorescent probe staining and an ATP determination kit.MDA-MB-231 cells were transfected with pcDNA3.1-EG-FP-POLG plasmids to overexpress POLG.The inhibitory effects of ddC on cell migration and invasion were detected in POLG-overexpressed MDA-MB-231 cells.Results POLG expression was higher in MDA-MB-231 cells than in normal mammary epithelial cells(MCF-10A)(P＜0.01).ddC inhibited cell viability in a dose-dependent man-ner.ddC inhibited the migration(P＜0.01)and invasion(P＜0.01)of MDA-MB-231 cells;however,it dis-played no significant inhibitory effects on cell viability in normal mammary epithelial cells(MCF-10A)at the same concentration.ddC downregulated the protein(P＜0.01)and mRNA(P＜0.01)levels of POLG,reduced mtD-NA copy number(P＜0.01)and downregulated mtDNA-coded NADH1,NADH2,ATPase6,COX-1 and COX-3 protein expression(P＜0.01)in MDA-MB-231 cells.Furthermore ddC inhibited mitochondrial content(P＜0.01)and ATP(P＜0.01)levels in MDA-MB-231 cells.POLG overexpression increased the migration(P＜0.05)and invasion(P＜0.05)abilities of MDA-MB-231 cells,while ddC did not significantly inhibit the migra-tion and invasion abilities of MDA-MB-231 cells overexpressing POLG.Conclusion ddC downregulates POLG ex-pression in MDA-MB-231 cells and inhibits mitochondrial biogenesis and ATP levels,thereby inhibiting the migra-tion and invasion of MDA-MB-231 cells.

Objective To explore the predictive value of immune inflammation combined with liver function hematological indicators for the metastasis of colorectal cancer.Methods A retrospective analysis of clinical data of 133 patients with colorectal cancer was conducted.The patients were divided into three groups based on disease progression after 24 months of postoperative follow-up:non-metastasis group(n=38),liver metastasis group(n=43),and non-liver distant metastasis group(n=52).The immune inflammatory markers and liver function hematological indicators of progression-free survival were analyzed.Nomogram prediction models were constructed using univariate and multivariate logistic regression analyses to identify risk factors for metastasis of colorectal cancer.The accuracy of the nomogram was validated using receiver operating characteristic(ROC)curve and calibration curve,and the clinical predictive efficacy was evaluated through decision curve and clinical impact curve.Results Univariate and multivariate logistic regression analyses showed that pan-immune-inflammatory value(PIV),prognostic nutritional index(PNI),and bile acid(BA)were independent predictors of colorectal cancer metastasis.The area under the ROC curve of the combined prediction of metastasis was 0.84;neutrophil/lymphocyte ratio(NLR)and BA were independent predictors of liver metastasis from colorectal cancer.The area under the ROC curve of the combined prediction of liver metastasis was 0.83;PIV and PNI were independent predictive factors for the occurrence of non-liver distant metastasis from colorectal cancer.The area under the ROC curve for the combined prediction of non-liver distant metastasis was 0.83.The calibration curve,decision curve,and clinical impact curve showed that the three models had good accuracy and net benefit value.Conclusion The nomogram constructed based on immune inflammation and liver function hematological indicators can predict the metastasis of patients with colorectal cancer and has high predictive efficacy and clinical application prospects.

Objective:To explore the role and mechanism of P311 in the differentiation of mouse skin fibroblasts (Fbs) into myofibroblasts.Methods:The study was an experimental research. Six 2-day-old male C57BL/6 mouse were used to extract skin Fbs by enzymatic hydrolysis method and routinely cultured. The 1 st to 3 rd passage cells were taken and divided into empty vector group transfected with empty adenovirus and P311 group transfected with P311 high expression adenovirus, and P311+myocardin-related transcription factor A (MRTF-A) small interfering RNA (siMRTF-A) group transfected with P311 high expression adenovirus and siMRTF-A according to the random number table. After 72 h of culture, the cell proliferation vitality of cells in 3 groups was detected by cell counting kit 8, the protein expressions of MRTF-A, α-smooth muscle actin (α-SMA), and serum response factor (SRF) in cells in 3 groups were detected by Western blotting, the collagen gel contraction assay was performed and the 72 h gel contraction rates in 3 groups were calculated. The sample numbers in the above experiments were all 3. The protein expressions of MRTF-A and SRF in cells, cytoplasm, and nucleus in cells in empty vector group and P311 group were detected by Western blotting, with sample number of 4. Results:After 72 h of culture, the cell proliferation vitality of cells in empty vector group, P311 group, and P311+siMRTF-A group was similar ( P>0.05). After 72 h of culture, compared with those in empty vector group, the protein expressions of MRTF-A, α-SMA, and SRF in cells in P311 group were significantly increased ( P<0.05), while the protein expressions of MRTF-A and SRF in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). Compared with those in P311 group, the protein expressions of MRTF-A, SRF, and α-SMA in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). The 72 h gel contraction rate showing cell contractility in P311 group was (84.8±6.2)%, which was significantly higher than (27.8±2.6)% in empty vector group and (24.7±3.2)% in P311+siMRTF-A group (with P values all <0.05). The 72 h gel contraction rates in empty vector group and P311+siMRTF-A group were similar ( P>0.05). After 72 hours of culture, the protein expressions of MRTF-A (with t values of 5.86 and 3.77, respectively, P<0.05) and SRF (with t values of 3.95 and 3.97, respectively, P<0.05) in cells and cytoplasm in P311 group were significantly higher than those in empty vector group, while the protein expressions of MRTF-A and SRF in the nucleus of cells were similar between the two groups ( P>0.05). Conclusions:P311 can promote the differentiation of fibroblasts into myofibroblasts through MRTF-A, and then participate in scar formation.

OBJECTIVES: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. METHODS: Utilizing data from the National Health and Nutrition Examination Survey collected between 2001 and 2010, including 13,142 United States adults (48.7% female and 51.2% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. RESULTS: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific results: the negative association between OBS and PhenoAgeAccel was more pronounced in male than in female. An analysis using restricted cubic splines revealed no significant non-linear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. CONCLUSIONS A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Objective:To investigate the effects of different chemotherapy dose intensity on the short-term efficacy and adverse reactions of patients with advanced colon cancer.Methods:A real-world database of patients with advanced colon cancer in Wangjing Hospital of China Academy of Chinese Medical Sciences and China-Japan Friendship Hospital from January 2017 to December 2020 was established, including 105 patients treated with the same chemotherapy regimen for two consecutive cycles. The patients were grouped according to the average relative dose intensity (ARDI) of chemotherapy, and the population differences, treatment regimens, short-term efficacy and adverse reactions of different chemotherapy dose intensities were evaluated. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of ARDI for short-term efficacy.Results:There were 31 patients in the high dose intensity group (ARDI≥80%) , 34 patients in the medium dose intensity group (80%0.05) . ROC curve analysis found that the area under the curve predicting objective response was 0.70, the sensitivity was 92.30%, and the specificity was 52.10% when the chemotherapy ARDI threshold was 64%. Conclusion:In the real world, colon cancer patients receiving high dose intensive chemotherapy have better objective response rate, and tumor markers decreased significantly. The baseline status of colon cancer patients receiving low dose intensive chemotherapy is poor, but there is no statistically significant difference in disease control rate between patients receiving low dose intensive chemotherapy and patients receiving high dose intensive chemotherapy, and the adverse reactions are controllable.

Objective To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. Methods A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. Results There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. Conclusion There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

Objective:To investigate the ultrasound image and pathological features of invasive fibromatosis, and to provide a basis for the diagnosis of invasive fibromatosis.Methods:The clinicopathological data of 22 patients pathologically diagnosed with invasive fibromatosis from January 2016 to March 2019 in Shanxi Provincial Cancer Hospital were retrospectively analyzed. The clinical, ultrasound and pathological data were also summarized.Results:Ultrasound images of invasive fibromatosis showed irregular morphology, unclear boundaries, uneven echo, spot-like or strip-shaped blood flow signals. The coincidence rate of ultrasound diagnosis was 59.1% (13/22), 3 cases were misdiagnosed as fibrous, fat and other sarcomas, 4 cases were misdiagnosed as nerve-derived tumors, 1 case was misdiagnosed as nodular fasciitis, and 1 case was misdiagnosed as gastrointestinal stromal tumor. The pathological characteristics of invasive fibromatosis were more typical, and the positive expression rate of vimentin and β-catenin in immunohistochemistry was 100.0% (22/22); the coincidence rate of preoperative pathological diagnosis of puncture was 78.6% (11/14), 1 case was misdiagnosed as nerve fiber tumor, 1 case was misdiagnosed as low-grade fibromyxoid sarcoma, and 1 case was misdiagnosed as nodular fasciitis.Conclusion:Invasive fibromatosis has a certain specificity in ultrasound and pathological diagnosis, which can be diagnosed and differentially diagnosed according to the ultrasound image and pathological characteristics.

Objective To explore hemodynamic performance of the aortic dissection after lesions, so as to provide a more scientific basis for patient treatment. Methods Based on computed tomography angiography (CTA) image data from a patient with complex Stanford B-type aortic dissection, the personalized aortic dissection models with different rupture shapes (H-type, O-type, and V-type) at proximal end of the aortic dissection were established. Combined with computational fluid dynamics (CFD) and morphological analysis method, distributions of the velocity at rupture section, the blood flow, the wall pressure and the wall shear stress (WSS) were analyzed. Results The flow velocity, the highest pressure difference and the WSS proportion at entrance of the H-shaped rupture showed larger hemodynamic parameters than those of the other two types. The risk of dissection rupture for type H was the largest, while type V was in the middle, and type O was the smallest. Conclusions This study provides an effective reference for further numerical analysis the cases and formulation of treatment plans.

With the development of modern medical technology,accurate resection of tumor and timely repair and repair of defective tissues and organs are important concerns in the field of tumor research.The precise excision of tumor,refers to the preoperative assessment of systemic and local detection based on detailed to personalized surgical planning,the use of precise operation in operation,ensure as much as possible while minimizing surgical trauma to patients after removal of the lesions,creating the optimal conditions of recovery for trauma patients.Repair and regeneration of defective tissues and organs refers to the deletion or damage of tissues and organs,and gradually resume its anatomical structure and function process under the action of a variety of cells,extracellular mechanisms and related regulatory factors.Then from the tumor resection,tumor resection and accurate regeneration after three point repair technology to change rapidly in the tissue of tumor plastic organ regeneration in tissue of origin.