The P53 gene has the important functions including induction of apoptosis, regulation of cell cycle, repair of DNA damage. The mutation of the P53 gene exists in more than 50% of human tumors and 13% of hematological malignancies. The P53 gene abnormality is closely related with the clinical course and prognosis of leukemia. The P73 or P63 gene, the member of the P53 family not only possesses similar to P53 activity of inducing apoptosis, activating transcription, but also plays different biological effects according to protein structural diversity, and even antagonises the function of the P53 gene. Researchers found that P73 or P63 gene also has the dual characteristics of the tumor suppressor and oncogene, and shows different expression and function in different types, different stages of leukemia. In this article, P53 family (P53, P73, P63) gene structure, biological function and the relationship of the three genes with the course, prognostic outcome, treatment and other clinical features of the leukemia are reviewed.
Gene Expression Regulation, Neoplastic ; Genes, p53 ; Humans ; Leukemia ; diagnosis ; genetics ; pathology ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo investigate the expression and significance of peroxisome proliferators-activated receptor gamma (PPAR gamma) in human glioma.

METHODSImmunohistochemical staining for PPAR gamma was performed using biopsy specimens of human glioma of various histological types. Expression of PPAR gamma and GFAP in glioma cell lines SWO-38, U251 and SHG-44 were analyzed using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSImmunohistochemical study showed that PPAR gamma was expressed in glioma tissues with positive rate of 37.5%. Western blotting and RT-PCR showed that PPAR gamma was expressed in both glioma cell lines SWO-38 and U251, but not in SHG-44 cells. However, high expression of GFAP was detected in SHG-44 cells.

CONCLUSIONPPAR gamma is associated with carcinogens of glioma. Actived PPAR gamma by agonist may be a novel approach to the treatment of glioma.

Blotting, Western ; Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Glial Fibrillary Acidic Protein ; biosynthesis ; genetics ; Glioma ; genetics ; metabolism ; pathology ; Humans ; Immunohistochemistry ; PPAR gamma ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo compare the impact of unilateral acute testicular ischemia on the hemodynamics and histology of the contralateral testis of the rabbits under consistent anesthesia with that of the rabbits in the conscious state.

METHODSForty-two healthy male white rabbits were randomly divided into an anesthetic group (Group A) to receive injection of sodium pentobarbital (PS) and a non-anesthetic group (Group B), each including a control group of 5 animals (A0 and B0), an incomplete testicular ischemia group of 8 (A1 and B1), and a complete testicular ischemia group of 8 (A2 and B2). Testicular ischemia models were constructed by color Doppler ultrasonography. Contrast-enhanced ultrasound (CEUS) was used to observe the perfusion of the contralateral testes before and after ligating and loosening the unilateral spermatic cord in each experimental group. The control animals also underwent CEUS and measurement of the heart rate (HR) and blood pressure (BP) at the corresponding time. Histological structure changes in the contralateral testes of the rabbits were observed in both anesthetic and conscious states.

RESULTSPS anesthesia markedly suppressed the HR and BP of the rabbits. The parameters in Groups of A0, A1 and A2 showed no statistically significant changes after unilateral ligation of the spermatic cord, while Groups B1 and B2 displayed significantly decreased peak-base difference (PBD) and prolonged arrival time (AT) and half time of descending peak intensity (HT). Groups A1, B1 and B2 showed significantly increased PBD and prolonged HT shortly after loosening the spermatic cord. Focal pathological and ultrastructural changes were observed in the contralateral testes of the ischemic rabbits, but no significant difference was found in Johnson's score in comparison with the controls. The apoptotic cells were remarkably increased in Groups A1, B1 and B2.

CONCLUSIONAcute testicular ischemia may induce injury to the contralateral testis to some degree, and a reflexive sympathetic response may cause hemodynamic changes in the non-anesthetic state. And the neural and vascular inhibitory effects of anesthesia could make insignificant changes of blood perfusion in the contralateral testis.

Animals ; Disease Models, Animal ; Ischemia ; diagnostic imaging ; pathology ; Male ; Rabbits ; Reperfusion Injury ; diagnostic imaging ; pathology ; Testicular Diseases ; diagnostic imaging ; pathology ; Testis ; blood supply ; diagnostic imaging ; pathology ; Ultrasonography

Objective: To evaluate the prognostic value of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in patients with diffuse large B cell lymphoma (DLBCL) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-eight patients with DLBCL treated at Peking University Cancer Hospital between November 2010 and December 2014 were assessed. All patients underwent PET/CT scanning prior to or after auto-HSCT. Correlation analysis was done based upon patients characteristics, PET/CT scan results and survival. Results: ①Among 48 patients, 27 was male, 21 female, median age was 43 (17-59) years old. ② Patients with negative pre-auto-HSCT PET/CT assessment demonstrated significantly better 3-year progression free survival (PFS) (87.1% vs 53.3%, χ(2)=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ(2)=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ(2)=22.75, P=0.001) and OS (97.1% vs 40.0%, χ(2)=21.09, P=0.002) were also significantly different between patients with negative and positive post-auto-HSCT PET/CT assessment. ③ Multivariate analysis indicated a significant association of PFS (HR=13.176, P=0.005) and OS (HR=20.221, P=0.007) with post-auto-HSCT PET/CT assessment. Number of prior treatment regimens was associated with PFS (HR=10.039, P=0.040). ④ Harrell's C index revealed that the value of combined use of number of prior treatment regimens and post-auto-HSCT PET/CT assessment was superior to either one used alone in PFS (Harrell's C values were 0.976, 0.869 and 0.927 in combined use, number of prior treatment regimens and post-auto-HSCT PET/CT assessment, respectively), and the combined use of ECOG performance status and post-auto-HSCT PET/CT assessment significantly increased the Harrell's C index in OS (Harrell's C values were 0.973, 0.711 and 0.919 in combined use, ECOG performance status and post-auto-HSCT PET/CT assessment, respectively). Conclusions: Post-auto-HSCT PET/CT assessment is the main predictor of outcomes in DLBCL patients receiving auto-HSCT. Combined use of post-auto-HSCT PET/CT assessment and number of prior treatment regimens and ECOG performance status is a better prognostic tool in patients with DLBCL undergoing transplantation.
Adolescent ; Adult ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18 ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; Young Adult

OBJECTIVEThis study was aimed to explore the effect of a novel histone deacetylase inhibitor Chidamide on apoptosis of human multiple myeloma(MM) cells and its relevance to DNA damage response(DDR).

METHODSThe cell proliferation was detected by MTT method, apoptosis and cell cycle distribution were analyzed by flow cytometry, the expression levels of targeted proteins were detected by Western blot, the DNA damage response was blocked by ATM kinase inhibitor KU-55933.

RESULTSChidamide inhibited RPMI 8226 cell proliferation in dose- and time-dependent manner and its IC50 values of 24,48,72 h were 9.6, 6 and 2.8 µmol/L respectively. Chidamide induced cell cycle arrest of RPMI 8226 cells in G0/G1 phase by upregulating the expression of P21. Chidamide triggered caspase-3 dependent apoptosis and upregulated expression of DDR-related proteins including γH2AX, pATM in RPMI 8226 cells. Pretreatment with ATM kinase inhibitor KU-55933 down-regulated expression of DDR related proteins induced by chidamide, thereby inhibiting DNA damage response and finally resulting in suppression of apoptotic cell death.

CONCLUSIONProliferative inhibtion, cell cycle arrest and apoptosis of multiple myeloma cells induced by chidamide involve DDR.

Aminopyridines ; Apoptosis ; Benzamides ; Caspase 3 ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; DNA Damage ; Down-Regulation ; Flow Cytometry ; Histone Deacetylase Inhibitors ; Humans ; Morpholines ; Multiple Myeloma ; Pyrones

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7(+) in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M(3) AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7(+) and CD7(-) patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7(+) group by Kaplan-Meier method. Results: In CD7(+) group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7(-) group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7(+) group comparing to those of CD7(-) group in AML patients with wild type CEBPA. There were no statistical difference between CD7(+) group and CD7(-) group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7(+) group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7(+)-CEBPA MT group, CD7(-) and CD7(+)-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion: The CEBPA mutation rate was higher in CD7(+) AML patients then that of CD7(-) patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.
CCAAT-Enhancer-Binding Proteins/genetics* ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Retrospective Studies

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 μg·g~(-1)) was higher than that in GFA(0.03-10.41 μg·g~(-1)) and GS(0.04-13.66 μg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.
Flavonoids/analysis* ; Alkaloids ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry ; Drugs, Chinese Herbal

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.
China ; Humans ; Kidney/surgery* ; Kidney Neoplasms/surgery* ; Laparoscopy ; Nephrectomy ; Retrospective Studies