Objec ive: o inves iga e he effec s of differen dose of bisoprolol on neurohormonal ac ivi y,cy okines,cardiac func ion,cardiac dea h in chronic sys olic hear failure pa ien s Me hods: One hundred and wen y chronic hear failure pa ien s were randomly divided in o large dose group (average 8 5? 1 2 mg) and small dose group (average 3 5?1 2 mg) he changes of norepinephrine (NE) ,angio ensionⅡ (AngⅡ) ,aldos erone (Ald) ,endo helin (E ) ,in erleukin 6 BF (IL 6) , umour necrosis fac or ? ( NF ?) Q ,plasm rennin ac ivi y (PRA) ,cardiona rin (ANP) ,brain na riure ic pep ide (BNP) ,cardiac func ion,cardiac dea h were observed Resul s:Af er rea men , he hear ra e were decreased in wo groups, p

Objective To study the mechanism of unscheduled Cyclin B1 expression at G_1 phase which is usually at G_2/M phase.Methods Human peripheral blood lymphocytes(PBL) from healthy volunteers were firstly activated by PHA and then went into cell cycle.The cells were collected at 0,36,48 and 60 h after activation and divided into two parts:one for Cyclins/DNA muhiparameter assay,and another for Post-sorting Western blot.Results After activation by PHA,Cyclin B1 and CDK1 of lymphocytes were expressed at G_1 phase.Conclusion Unscheduled Cyclin B1/CDKl probably contributes to lymphocytes in vivo into cell cycle.

The recurrence of colorectal polyps is caused by various factors and leads to the carcinogenesis of colorectal cancer, which ranks third in incidence and fourth in mortality among cancers worldwide. The potential risk factors for colorectal polyp recurrence have been demonstrated in multiple trials. However, an article that pools and summarizes the various results is needed. This review enumerates and analyzes some risk factors in terms of patient characteristics, procedural operations, polyp characteristics, and dietary aspects to propose some effective prophylactic measures. This review aimed to provide a reference for clinical application and guide patients to prevent colorectal polyp recurrence in a more effective manner.

Objective To investigate a more pedect method for a nice outward appearance of a reconstructed thumb.Methods A free one-stage plasty second toe transfer for thumb reconstruction by interchanging the whole skin-nail flap from the great toe with another one from the second toe.Results There were 12 cases in this group,following-up 6-9 months in 8 cases,7 cases was excellent and 1 cases was good.The reconstructed thumb got a nice looking and more normal function while no blight to the great toe occurred.Conclusion It is an effective new procedure in ameliorating outward appearance of the reconstructed thumb by transferring the free moulded second toe.

Objective To explore the diagnostic value of Likert score and EPE grade score based on multiparameter magnetic resonance imaging(mpMRI)for extracapsular extension in prostate cancer(PCa).Methods The MR imaging and histopathology data from 272 PCa patients were analyzed retrospectively.All patients underwent mpMRI examination within 2 months before radical prostatectomy.Two radiologists with over 10 years of experience assessed the mpMRI images according to the Likert score and EPE grade score,respectively,and compared with pathological findings.The consistency between the two radiologists was evaluated by weighted Kappa test.The statistical analysis was performed using MedCalc 20.0 software.The sensitivity,specificity and other indicators were calculated to analyze the optimal cut-off value of Likert score and EPE grade score for diagnosing extracapsular extension in PCa.The area under the curve(AUC)was used to compare the diagnostic performance of the two scoring systems for extracapsular extension in PCa.Results Among 272 PCa patients,there were 45 cases with extracapsular extension and 227 cases without extracapsular extension.The weighted Kappa coefficients were 0.730 and 0.820 for Likert score and EPE grade score,respectively,indicating good consistency.The optimal cut-off values for diagnosing extracapsular extension in PCa were Likert score 3 and EPE grade score 2.The sensitivity and specificity were 68.8%and 77.5%for Likert score 3,and 64.4%and 84.5%for EPE grade score 2,respectively.Both Likert score(AUC=0.780)and EPE grade score(AUC=0.797)had high accuracy in predicting extracapsular extension in PCa,with no significant difference(P>0.05).Conclusion Both Likert score and EPE grade score have good diagnostic performance in detecting extracapsular extension in PCa,which provides important diagnostic basis for clinical staging of PCa.

Objective:To investigate the clinical efficacy of early versus delayed open reduction and internal fixation in the treatment of tibial pilon fracture. Methods:Sixty patients with tibial pilon fractures admitted to Zhejiang Veteran Hospital from May 2018 to May 2021 were included in this study. They were randomly divided into a control group and a study group ( n = 30/group) using the coin-tossing method. Patients in the control group underwent early reduction and internal fixation within 3 days after injury. Patients in the study group underwent delayed reduction and internal fixation during 7-14 days after injury. The time to bone fracture healing and the time to independent weight-bearing walking were recorded. At 3 and 6 months after surgery, the American Orthopedic Foot and Ankle Society score, Visual Analogue Scale score, clinical efficacy, and incidence of complications were compared between the two groups. Results:The time to bone fracture healing and the time to independent weight-bearing walking in the study group were (8.23 ± 0.63) weeks and (11.77 ± 0.82) weeks, respectively, which were significantly shorter than (9.57 ± 0.86) weeks and (13.40 ± 0.93) weeks in the control group ( t = 6.87, 7.21, both P < 0.001). At 3 months after surgery, American Orthopedic Foot and Ankle Society score in the study group was significantly higher than that in the control group, and the Visual Analogue Scale score in the study group was significantly lower than that in the control group ( t = 6.69, 5.16, both P < 0.001). Overall excellent and good rate of clinical efficacy in the study group was significantly higher than that in the control group (86.6% vs. 63.3%, χ2 = 4.35, P = 0.037). At 6 months after surgery, there were no significant differences in American Orthopedic Foot and Ankle Society score and Visual Analogue Scale score between the two groups ( t = 0.96, 1.12, P = 0.339, 0.267). At 6 months after surgery, there was no significant difference in the overall excellent and good rate of clinical efficacy between the study and control groups (96.6% vs. 90.0%, χ2 = 0.26, P = 0.605). The incidence of complications in the study group was significantly lower than that in the control group (3.3% vs. 26.6%, χ2 = 4.70, P = 0.030). Conclusion:Delayed open reduction and internal fixation after reducing injury to the soft tissue of the affected limbs can effectively shorten the rehabilitation cycle of tibial pilon fracture, increase short-term efficacy, and decrease the risk of postoperative complications.

Transforming growth factor-β (TGF-β) exerts apoptotic effects on various types of malignant cells, including liver cancer cells. However, the precise mechanisms by which TGF-β induces apoptosis remain poorly known. In the present study, we have showed that threonine 32 (Thr32) residue of FoxO3 is critical for TGF-β to induce apoptosis via Bim in hepatocarcinoma Hep3B cells. Our data demonstrated that TGF-β induced FoxO3 activation through specific de-phosphorylation at Thr32. TGF-β-activated FoxO3 cooperated with Smad2/3 to mediate Bim up-regulation and apoptosis. FoxO3 (de)phosphorylation at Thr32 was regulated by casein kinase I-ε (CKI-ε). CKI inhibition by small molecule D4476 could abrogate TGF-β-induced FoxO/Smad activation, reverse Bim up-regulation, and block the sequential apoptosis. More importantly, the deregulated levels of CKI-ε and p32FoxO3 were found in human malignant liver tissues. Taken together, our findings suggest that there might be a CKI-FoxO/Smad-Bim engine in which Thr32 of FoxO3 is pivotal for TGF-β-induced apoptosis, making it a potential therapeutic target for liver cancer treatment.
Apoptosis ; genetics ; Apoptosis Regulatory Proteins ; biosynthesis ; Bcl-2-Like Protein 11 ; Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; genetics ; pathology ; Membrane Proteins ; biosynthesis ; Proto-Oncogene Proteins ; biosynthesis ; Threonine ; genetics ; Transforming Growth Factor beta ; genetics

Objective:To explore the correlation between post-transplant non-HLA antibodies and humoral rejection(HR)after kidney transplantation(KT).Methods:A retrospective study was conducted for KT recipients with non-HLA antibody level detected from September 2019 to January 2021.The recipients with biopsy confirmed HR and donor-specific HLA antibodies negative or feeble positive at the time of HR were designated as HR group while recipients with stable renal allograft function from 2 weeks post-KT to the time of detecting non-HLA antibody as stable group.The levels of HLA antibody, MHC classⅠchain-related gene A(MICA)antibody and 32 non-HLA antibodies were tested by Luminex single antigen bead and the levels of angiotensin Ⅱ type 1 receptor(AT1R)antibody quantified by enzyme-linked immunosorbent assay (ELISA). Inter-group differences in positive rate of non-HLA antibodies and number of positive non-HLA antibodies were analyzed.Results:Twenty-four recipients had positive non-HLA antibodies while the remainders had no positive non-HLA antibodies.Three HR recipients were positive for actin antibody, collagen Ⅲ antibody, glutathione S-transferase theta-1 antibody or IFN-γ antibody respectively.However, all four non-HLA antibodies of stable recipients were negative.There was significant inter-group difference( P=0.017). Four HR recipients were positive for collagenⅡantibody while only 1 stable recipient was positive for collagenⅡantibody.The positive rate of collagenⅡ antibody was significantly higher in HR recipients than that in stable recipients( P=0.023). HR recipients had an average of 2.36 positive non-HLA antibodies while stable recipients had an average of 0.90.There was significant inter-group difference ( P=0.008). Conclusions:A high level of non-HLA antibodies may elevate the risk of HR after KT.

Objective To investigate the in vivo radioprotective effect of adenosine triphosphate (ATP) on radiation damage induced by high dose γ-ray ionizing radiation(IR) in mice.Methods Specific pathogen-free C57BL/6 female mice were randomly divided into IR group and IR+ATP group by body weight,with 10 mice in each group.All the mice were treated with a 8 Gy one-time and high-dose whole body γ-ray irradiation.Within 6 h after irradiation,mice were injected intramuscular injection of 150 pl sodium chloride solution (9 g/L) for IR group,and 150 μl ATP solution (6 mg/kg) for IR+ATP group,respectively.The drug was administered once a day until the death of the animal.The mean survival days,survival rate,body weight and major organ coefficients in both groups were measured.Results The average survival days of mice in IR group and IR +ATP group were 6.5 d and 9.6 d,respectively.The survival rate of the mice in IR+ATP group was higher than that in IR group (P＜0.01).The body weight values of the mice in IR+ATP group was higher than that in IR group on the after the 4th day post-irradiation,and the differences were statistically significant (all P＜0.05).Except for heart and stomach,the organ coefficients of liver,spleen,lung,and kidney in IR +ATP mice were higher than those in IR group,and the differences were statistically significant (all P＜0.05).Conclusion ATP has certain radiation protection effect,and it can reduce the radiation damage of mice induced by high-dose (8 Gy) γ-ray IR so as to increase the survival rate.

Objective:To confirm the mechanism of Sedum alfredii extract (SafE) alleviating radiation injury in human small intestinal epithelial cells (HIEC-6). Methods:HIEC-6 cells were divided into 4 groups, including control group (Con), irradiation group (IR), SafE alone group (SafE) and SafE plus irradiation group (SafE+ IR). All of the SafE groups were treated with 0.02 g/ml (W/V) SafE for 24 h. Cell viability (CCK-8 method ) and intracellular ROS levels were investigated at 24 h after 2, 4, and 6 Gy irradiation. Samples were taken at 24 h after 4 Gy irradiation for transcriptome analysis, and the intracellular E3 ubiquitin ligase PRKN expression level was measured. The thickness of endoplasmic reticulum was detected at 24 h after 4 Gy irradiation using fluorescent dye.Results:SafE could maintain cell viability after irradiation ( t=2.94-10.40, P<0.05), and significantly reduced the level of ROS in the irradiated cells ( t=-13.29--4.53, P<0.05). PRKN was preliminarily verified to be the target gene of SafE that maintained PRKN transcript level and endoplasmic reticulum thickness after irradiation (IR group vs. Con group: t=-5.55, 3.27, P<0.05, SafE group vs. SafE+ IR group: P>0.05). Conclusion:SafE is effective in maintaining ER thickness and reducing cellular radiation damage and its target gene PRKN could be regulated by ionizing radiation.