DNA topoisomerases-mediated DNA damages are generated from exogenous and endogenous effects, which need to be metabolized or repaired to maintain genome stability involving in many of repair enzymes. Tyrosyl-DNA phosphodiesterase 1 (TDP1) and tyrosyl-DNA phosphodiesterase 2 (TDP2) are two DNA repair enzymes discovered recently. TDP1 and TDP2 have the ability to hydrolyze the tyrosyl-phosphodiester bond of the phenol of tyrosine with 3'-and 5'-DNA end, respectively, which are contained in the metabolites of the damaged DNA mediated by topoisomerase 1 and topoisomerase 2, respectively. The abnormal activation and expression of TDP1 or TDP2 is the important reason for cancer development. Therefore, TDP1 and TDP2 have been regarded as potential targets in cancer therapy. In this review, we discuss the rationales of their potential as targets and development of their inhibitors together with topoisomerase poisons or DNA damaging agents.

Objective To investigate ISO 7206 standard used as a guidance for clinical selection of total hip prosthesis. Methods Kinematics and dynamics process of normal walking gait was simulated by establishing a numerical musculoskeletal model; the corresponding finite element model of total hip prosthesis was constructed, and gait loads were applied to calculate stress distribution on prosthesis, which were compared with that on ISO finite element model. ResultsPeaks of hip joint reaction forces were achieved at 20% gait and 54% gait during normal walking gait, which were used as gait loads for finite element simulation, and the results showed that the maximum Von Mises stress of prosthesis was reached at 20% gait. The maximum Von Mises stress of prosthesis in loosening model was higher than that in non-loosening model, and some differences existed in the distribution pattern. The maximum stresses of prosthesis both under ISO loads and gait loads by different body weights were analyzed and compared, and the maximum stress of prosthesis under ISO loads was equivalent to that under gait loads by body weight between 108 kg and 142 kg. ConclusionsThe prosthesis that passed ISO test can meet the strength requirement for normal gait loads of 100 kg body weight.

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

The precondition of accurate gastric cancer surgery is precise assessment of lymph node metastasis. To date, no imaging modality achieves both high sensitivity and high specificity in detecting lymph node metastasis in gastric cancer. Intraoperative sentinel node tracing and biopsy are the most popular method to identify the localization of tumor cell, but is limited to early gastric cancer. Nano-composite materials, designed for tumor imaging and tracing, show us a newly emerging domain for tumor detection in gastric cancer. The function of these nano-composite materials to detect lymph node metastasis in gastric cancer relies on the effective backflow of lymph system. However, the lymph vessels can be obstructed by tumor cells in advanced gastric cancer, which may restrain the application of these nanoparticles. Therefore, more methods to detect lymph node metastasis in gastric cancer should be explored. This review summarizes the characteristic of the targeted nanosphere. Based on the reported studies, a novel idea is conceived that targeted multifunctional nanosphere may be a potential method to achieve precise assessment of lymph node metastasis in gastric cancer.
Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Stomach Neoplasms ; pathology

OBJECTIVETo investigate the factors that affect the prognosis of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL).

METHODSThe clinical data of 116 patients with pathologically confirmed PGI-NHL we treated from January 1993 to December 2003 were analyzed retrospectively. Kaplan-Meier survival analysis was used for analyzing the survival of the patients, and Log-rank test was performed to compare the survival rates in relation to different prognostic factors.

RESULTSThe 3-year and 5-year survival rates of the patients were 63.8% (74/116) and 48.2% (40/83), respectively. Univariate analysis revealed that the factors affecting the prognosis of the patients included the presence of B symptom, tumor size, clinical stage, pathological type, depth of invasion, and treatment methods. The patients with B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, and invasion beyond the serosa who received only surgical management had poorer prognosis than those free of B symptom with tumor size <10 cm, early clinical stage (stages I(E) and II(E)), B-cell type, and submucosal or serosal invasion managed with chemotherapy alone or in combination with surgery. Multivariate analysis showed that B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, invasion beyond the serosa, and surgery alone were independently associated with poor prognosis.

CONCLUSIONThe tumor size, clinical stage, pathological type, treatment methods are the independent factors affecting the prognosis of patients with PGI-NHL.

Adolescent ; Adult ; Aged ; Child ; Female ; Gastrointestinal Neoplasms ; diagnosis ; mortality ; pathology ; Humans ; Kaplan-Meier Estimate ; Lymphoma, Non-Hodgkin ; diagnosis ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo describe the characteristics of child pedestrian traffic injuries among aged 0-14 years old in Guangzhou city and to provide information on road, vehicle and human injuries in pedestrian.

METHODSA database of all motor vehicle crashes involving child pedestrian traffic injury cases over a five-year period (2000-2004), was from the police department.

RESULTSThe annual pedestrian traffic injury rates on incidence, mortality and case fatality were 17.63/ 1,100,000, 1.78/ 100,000 and 10.07% respectively. Both incidence rate and mortality peaked in the 5-9 age group were 26.80/ 100,000 and 2.57/ 100,000, with case fatality peaked in the 0-4 age group (13.29%). For males, the incidence (20.98/ 100,000) and mortality (2.00/ 100,000) were higher than that in females (13.83/ 100,000, and 1.52/ 100,000). The main injured parts of body would include multi-areas (40.34%), head (26.75%) and lower limbs (21.53%). 10.07% of the cases died and 66.18% and 23.75% of them having had severe and slight injures. The major causes were due to drivers (57.50%) and pedestrians (33.47%) faults with top three responsible vehicles were cars (40.14%), two-wheeled motorcycles (34.38%) and vans (22.15%).

CONCLUSIONData from pediatric pedestrian injury poses a threat to children and adolescents, data suggesting that it is important to change behaviors of both drivers and pedestrians.

Accidents, Traffic ; statistics & numerical data ; Adolescent ; Age Distribution ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Wounds and Injuries ; epidemiology

BACKGROUNDCalcium phosphate cement (CPC) is a biocompatible and osteoconductive bone substitute, and recombinant human bone morphogenetic protein-2 (rhBMP-2) has strong osteoinductibility, therefore we developed a composite bone substitute with CPC and rhBMP-2 and evaluate its reconstruction effect in rabbit orbital defect.

METHODSThirty-six rabbits were randomly divided into two groups and a 5 mm × 5 mm × 2 mm bone defect in the infraorbital rim was induced by surgery in each orbit (72 orbits in all). The orbital defects were treated with pure CPC or composite of CPC and rhBMP-2. The osteogenesis ability of different bone substitute was evaluated by gross observation, histological examination, histomorphometrical evaluation, compressive load-to-failure testing, and scanning electron microscope (SEM).

RESULTSGross observation showed that both bone substitutes were safe and effective for reconstruction of orbital defect. However, histological examination, histomorphometrical evaluation and SEM showed that CPC/rhBMP-2 group had faster speed in new bone formation and degradation of substitute material than CPC group. Compressive load-to-failure testing showed that CPC/rhBMP-2 group had stronger compressive strength than CPC group at every stage with significant difference (P < 0.05).

CONCLUSIONComposite of CPC/rhBMP-2 is an ideal bioactive material for repairing orbital defect, with good osteoconductibility and osteoinductibility.

Animals ; Bone Cements ; therapeutic use ; Bone Morphogenetic Protein 2 ; therapeutic use ; Bone Substitutes ; therapeutic use ; Calcium Phosphates ; therapeutic use ; Female ; Male ; Microscopy, Electron, Scanning ; Orbit ; pathology ; surgery ; ultrastructure ; Osteogenesis ; Rabbits ; Recombinant Proteins ; therapeutic use ; Reconstructive Surgical Procedures ; methods ; Transforming Growth Factor beta ; therapeutic use

OBJECTIVETo study the correlation between noise and blood pressure and/or hypertension, and its age characteristic.

METHODSThe pure tone audiometric and blood pressure examinations were performed in 14537 workers from 157 factories. Hearing impairment was used as a surrogate indicator of cumulated noise exposure. The associations of hearing impairment and duration of noise exposure with blood pressure and hypertension were analyzed respectively after age and gender stratification.

RESULTSMost of the objects were males (81.2%), younger than 35 years old (77.8%), and the duration of exposure to noise was less than 5 years (73.6%). The prevalence of hearing impairment in males was significantly higher than that in males, and increased with age and duration of noise exposure. Only in males with age younger than 35 years old, the systolic and diastolic blood pressures of subjects with sensorineural hearing loss significantly enhanced, and the diastolic blood pressure and prevalence of hypertension increased with duration of noise exposure. The risk of hypertension in males with sensorineural hearing loss significantly increased, the odds ratios in subjects with age younger than 35 years old and with age older than 35 years old were 3.0 (95%CI: 1.5 ∼ 6.1) and 2.1 (95%CI: 1.2 ∼ 3.4), respectively.

CONCLUSIONThe severe hearing impairment induced by noise was associated with hypertension. It is suggested that people should pay attention to the effects of noise on hypertension in young workers.

Adult ; Blood Pressure ; Female ; Hearing Loss, Noise-Induced ; epidemiology ; Humans ; Hypertension ; epidemiology ; Male ; Noise, Occupational

OBJECTIVETo assess the therapeutic efficacy and adverse effects of endogenetic field hyperthermia (EFH) in combination with L-OHP /LV / 5-FU in the treatment of advanced gastric cancer.

METHODSThis study included 147 surgical patients with stage II-IV gastric cancer, who received postoperative chemotherapy with FOLFOX (L-OHP 85 mg /m square, 3 h intravenous infusion, followed by infusion of LV at 200 mg /m square in 2 h, intravenous injection of 5-Fu at 400 mg /m square, and intravenous infusion of 5-FU at 3000 mg /m square in 48 h). Eight treatment cycles (each lasting for 14 days) were administered. In 68 cases randomly selected from the cohort, EFH was performed on the first and third days (treatment group), but not in the other 79 cases (control group).

RESULTSThe response rate was 68.4% in the treatment group and 36.4% in the control group, showing significant difference between them (P<0.05). The 1-year survival rate was 88.2% in the treatment group, similar to the rate of 81.0% in the control group (P< 0.05), but the 3, 5-year survival rates in treatment group (67.6% and 30.9%) was significantly higher than those in the control group (47.6% and 15.4%, P<0.05). The adverse effects were similar between the two groups.

CONCLUSIONEFH combined with the chemotherapeutic regimen FOLFOX might improve the therapeutic effect of stage II-IV gastric cancer without obviously increasing the adverse effects.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Combined Modality Therapy ; Female ; Fluorouracil ; therapeutic use ; Humans ; Hyperthermia, Induced ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Organoplatinum Compounds ; therapeutic use ; Stomach Neoplasms ; drug therapy ; pathology ; surgery ; therapy ; Treatment Outcome

OBJECTIVETo investigate the dynamic expression of PTEN in fibrogenic liver tissue of rats and its effect on the activation and proliferation of hepatic stellate cells (HSC).

METHODSA rat model of hepatic fibrosis was established by common bile duct ligation (BDL). The expressions of PTEN in the rat liver tissues were detected by immunohistochemical staining, Western blot and real-time PCR assay. The expressions of PTEN in activated HSC in the rat liver tissues were detected by immunofluorescence double labeling confocal laser scanning microscopy. The alpha-SMA in the rat liver tissues was determined by immunohistochemical staining.

RESULTSThe immunohistochemical staining indicated that there was extensive expression of PTEN in the liver tissues of normal rats, it was expressed mainly in the cytoplasm of the HSC. With the aggravation of hepatic fibrosis, the expression of PTEN in the hepatic tissues decreased gradually (P less than 0.01), while the alpha-SMA positive cells in the hepatic tissues increased significantly (P less than 0.01). The expressions of PTEN protein and mRNA in the rat liver tissues at week 1, 2, 3 and 4 after BDL were all lower than those in the sham operation group (P less than 0.01), and the expressions gradually decreased with the development of hepatic fibrosis (P less than 0.01). Immunofluorescence double labeling confocal laser scanning microscopy showed that PTEN were expressed extensively in activated HSC, especially in the cytoplasm, and with the development of hepatic fibrosis, the PTEN-expressing activated HSC accounted for an increasingly smaller percentage of total activated HSC.

CONCLUSIONThe expressions of PTEN mRNA and protein in rat fibrogenic liver tissues were downregulated, and their expressions in HSC in vivo also decreased. The dynamic expressions of PTEN in liver tissues had a significant negative correlation with the activation and proliferation of HSC.

Animals ; Cell Proliferation ; Hepatic Stellate Cells ; cytology ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; PTEN Phosphohydrolase ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley