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.

Glaucoma is rarely complicated by retinitis pigmentosa (RP). To provide clinical evidences for this rare situation, we report the concurrence of these two diseases in two children of a Chinese family. In the present two-child Chinese family without positive history, the older sister presented with bilateral sector RP and coexisting chronic angle-closure glaucoma, and the brother with bilateral whole RP but without coexisting glaucoma. Clinical evidences in concurrence of variants of RP and glaucoma because of possible different gene mutations from the same genetic background represent a rare situation, which may provide clues for future researches in molecular pathogenesis of these rare diseases.
Female ; Glaucoma ; diagnosis ; Humans ; Retinitis Pigmentosa ; diagnosis ; Young Adult

Oxidative stress is implicated in male infertility and significantly higher reactive oxygen species are detected in 25% of infertile males. Although different agents of various alternative medicines, including traditional Chinese medicine, have been tried with varying success, evidence remains limited on whether and how much herbs or supplements might help increase the anti-oxidant ability of the sperm. This study examined the anti-oxidative effects of icariin, a flavonoid isolated from Herba Epimedii, on the human sperm. We prepared the FeSO4/H2O2-damaged human sperms, which were co-cultured with icariin in vitro, and then observed the changes of the sperm by employing Raman micro-spectroscopy. The results showed that Raman mapping with a 514 nm excitation laser allowed clear differentiation of the nucleus, neck, and, in particular, the mitochondria-rich middle piece of a human sperm cell. The effect of icariin on different organelles of the sperm was quantified by localized spectral Raman signatures obtained within milli-seconds, and icariin could keep the "Raman fingerprint" of the human sperm the same as the control groups, suggesting that icariin could protect the human sperm from being damaged by FeSO4/H2O2. Icariin may serve as a tonifying and replenishing agent of herbal origin for enhancing reproductive functions.

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

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

OBJECTIVETo compare the differences of injuries and recovery between video-assisted thoracoscopic surgery (VATS) and mini-thoracotomy (MT) in patients with clinical early stage non-small cell lung cancer (NSCLC) after lobectomy.

METHODSFrom March 2004 to December 2006, 47 consecutive patients with early stage NSCLC with a diameter of tumor less than 6 cm were recruited and randomized to VATS group and MT group. Incision length, duration of operation and intraoperative blood loss were recorded. Postoperative pain was assessed using a visual analogue scale before operation and daily for the first 7 days after operation. The serum levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured by cytometric bead array before operation and at 4, 24, and 48 h after operation. Karnofsky performance status (KPS) was assessed before operation and daily for the first 7 days after operation.

RESULTSIncision length was (6.0 +/- 0. 9) cm in the VATS group and (12.5 +/- 1.5) cm in the MT group. There was no significant difference in duration of operation and intraoperative blood loss between the VATS group and the MT group. Postoperative pain was significantly less in the VATS group in the 5th to 7th day postoperatively (P < 0.05). There was no significant difference of serum concentrations of IL-6 and IL-10 between the VATS group and the MT group at 4, 24, and 48 h after operation. KPS score was significantly higher in the VATS group on 2nd to 7th day postoperatively (P < 0.05).

CONCLUSIONCompared with MT, VATS for lobectomy has less postoperative pain, faster recovery, but can't reduce postoperative release of cytokines.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; surgery ; Double-Blind Method ; Female ; Humans ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Pain, Postoperative ; prevention & control ; Pneumonectomy ; methods ; Prospective Studies ; Thoracic Surgery, Video-Assisted ; Thoracotomy

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

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