Genomic instability is one of the most pervasive characteristics of cancer cells,and DNA damage response (DDR) pathway plays a crucial role in genomic stability.The DDR pathway is a complex signaling network,which involves cell DNA repair,apoptosis and cell cycle regulation.Deficiencies in these repair pathways can result in several different genetic disorders,including cancer.Targeted therapy based on inhibiting the DDR pathway in cancers offers a novel therapy strategy for patients with tumors lacking specific DDR functions.Many small-mole-cule compounds targeting DDR pathway are typically developed for solid cancer therapy.The poly (ADP-ribose) polymerase (PARP) inhibitor is a kind of DDR inhibitors which exploits the principle of synthetic lethality to selectively kill cancer cells.This review highlights the molecular mechanisms of PARP inhibitor action,the progress of PARP inhibitors in cancer therapy,drug resistance and the challenge of PARP inhibitor in the future.

The therapeutic effects and mechanisms of traditional Chinese kidney-tonifying drugs in treating osteoporosis have become the focus under study. Pharmacological studies have shown that traditional Chinese kidney-tonifying drugs are promoters for the proliferation of osteoblasts, inhibitors for the activity of osteoclasts, regulators for the estrogen level and its receptor, plays important roles in promoting osteogenesis and suppressing adipogenesis of marrow mesenchymal stem cells (MSCs), modulating the function of OPG/RANK/RANKL system and the metabolism of calcium and phosphorus, as well as antioxidation. The anti-osteoporotic active ingredients and pharmacological action mechanism of traditional Chinese kidney-tonifying drugs are summarized from the perspective of molecular and cell biology in this paper, so as to provide references for the study of their mechanism of anti-osteoporosis and for the development of traditional Chinese kidney-tonifying and bone-strengthening drugs.
Animals ; Bone and Bones ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Kidney ; drug effects ; physiopathology ; Osteoporosis ; drug therapy ; physiopathology

Background Treatment of corneal ulceration by transplanting drug-loaded amniotic membrane has been used widespreadly abroad,however,seldom study is found in China up to now.Objective This study was to explore the sustained release property and the efficacy of the drug-loaded amniotic membrane.Methods The bacteriostatic area of amniotic membrane fragments immersed with different concentrations (5,20,30 g/L) of levofloxacin for different time points (5,15,30,60 minutes) was evaluated by in vitro test.Bacterial corneal ulceration models were established in 20 rabbits by injected 0.7 MCF staphylococcus aureus suspension (0.1 ml) into the central corneal stroma to form the cloudy area of 4.0-6.0 mm.Then the rabbits were randomized into two groups.Regular amniotic membrane transplantation was performed laterally and 0.5％ levofloxacin drops was topically administered after operation in the amnion+levofloxacin drops group,and drug-loading amnion transplantation was used in the drug-loading amnion group.Aqueous humor of 0.1 ml was collected in 30 minutes,1 hour,2,3.5,5.5 hours after levofloxacin was administered and 1 day,3,7,10,14,21 days after operation for the detect of levofloxacin level with high-performance liquid chromatography.The corneal symptom was scored based on McNeill's criteria in 1 week,2 weeks and 4 weeks and the ulceration area was assessed under the slit lamp in the first week.The pathological examination was carried out in the fourth week after surgery.Results The mean bacteriostatic area was bigger with the increase of levofloxacin concentration,and bacteriostatic area in amnion immersed for 15 minutes was bigger than that of 5 minutes (P＜0.01).The levofloxacin concentration of aqueous humor after transplantation was decreased by extending the time,and that in 30 minutes and 5.5 hours after operation was (0.873±0.264) mg/L and (0.106±0.027) mg/L,respectively,in the amnion+levofloxacin drops group,and that in day 1,3,7 after surgery in the drug-loading amnion group was higher than at 30 minutes in the amnion+levofloxacin drops group,showing all significant differences (all P =0.00).In the first,second and fourth week after operation,the corneal symptom score was 1.7±0.6,1.3±0.5,0.2±0.4 in the drug-loading amnion group and 2.2±0.8,2.0±0.6,1.5±0.8 in the amnion+ levofloxacin drops group,with the significant differences among the different groups and time points (Fgroup =9.49,P =0.01 ;Ftime =22.96,P=0.01).The corneal ulceration area was (1.6±0.6) mm2 in the drug-loading amnion group and (3.2±0.8) mm2 in the amnion+levofloxacin drops group 1 week after operation,showing a significant difference between them (t =3.98,P =0.00).Histopathological revealed that the various layers of cornea tissue appeared irregular arrangement in the amnion + levofloxacin drops group 4 weeks after operation with 1-2 layers of new squamous epithelium.Disorder hypothallus structure,more inflammatory cells and residual vascular cavity were visible.However,new squamous epithelium of 4-5 layers was seen in the drug-loading amnion group,and inflammatory cells and residual vascular cavity were less than the amnion+levofloxacin drops group 4 weeks after operation.Conclusions Levofloxacin-loaded amniotic membrane can sustained release levofloxacin and maintain an effective drug concentration in aqueous humor,which improves the treating efficacy for staphylococcus aureus corneal ulceration.

Objective To explore the effect of minimally invasive clinical pathway in patients after car-diac interventional therapy. Methods One hundred and twenty patients who received cardiac interventional therapy from June 2005 to October 2006 were divided into the control group and the observation group.The control group received routine nursing while the observation group adopted minimally invasive clinical pathway of nursing.The nursing effect in the two groups was compared. Results The mean hospitalized duration, sat-isfaction degree and health knowledge level in the observation group were superior to those of the control group (P ＜ 0.05). Conclusions The adoption of minimally invasive clinical pathway in patients after cardiac inter-ventional therapy could increase working efficiency nd ensure the nusing quality.

Objective To analyse the suspected hereditary non-polyposis colorectal cancer (HNPCC) in mismatch repair protein (MMR) expression of hMLH1 and hMSH2. Methods Immunohistochemical staining method was used for the detection of hMLH1 and hMSH2 protein expression in 193 cases suspected HNPCC patients, the deletion of MMR proteins was identified as highly suspected HNPCC cases. Results Of the 193 patients with suspected HNPCC hMLH1/hMSH2 abnormal expression rate was 29.02%; ≤30 years old was 40%, 31 ~ 40 years old was 28.05%, 41 ~ 50 years old was 28.71%,3 suspected HNPCC showed the deletion of hMLH1/hMSH2 protein expression at the same time ,; In the right colon , the left half colon and rectal anomaly detection rates were 40.74%, 32.65%and 18.89%; hMLH1/hMSH2 deletion was 46.15%with family history. Conclusions The deletion of MMR protein is closely related to age,site and family history in suspected HNPCC, and the deletion of hMLH1 is an important factor to induce early-set colorectal cancer. The deletion of hMLH1/hMSH2 at the same time indicates that hMLH1/hMSH2 genes may play important role in the incidence of HNPCC.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Pneumoconiosis ; diagnostic imaging ; Radiography, Thoracic ; methods ; Tomography, X-Ray Computed

Teachers should have a good understanding of characteristic of Pathology Practical Training and enhance language communication competence,especially the expression ability in medical English.Meanwhile,it is essential for teachers to establish harmonious relationship with international students.

Objective: To investigate the effects of culture medium osmolarity on the proliferation of human hepatoma cell line HHCC. Methods:Cell proliferation was analyzed by MTT assay and cell cycle analysis was carried out by flow cytometry. Results:Hyperosmolarity decreased significantly the absorbance (A) of HHCC cells and cell number, and hyposmolarity have counter effects. Compared with control, hyperosmolarity blocked cell cycle progression at the G 1 phase, while hyposmolarity accelerated cells into S phase from G 1 phase, and the effect of hyposmolarity was weakened by chloride channel blocker NFA. Conclusion:Culture medium osmolarity influenced the proliferation of HHCC cells by mediating cell cycle.

Abstract?AIM:To study the Influence and outcomes of eye healthcare information teaching for the visual development of children under“combination of medicine and education” in kindergartens.?METHODS:The children(5-6 years old) were randomly selected from 6 kindergartens in Nanjing, 3 in Yuhua District as the experimental group, and the other 3 in Jianye District as the control group.A one-year follow-up was conducted to evaluate the difference of visual development, including the rate of low vision, rate of referral caused by refractive abnormality, rate of astigmatism, the average of the equivalent spherical lens and the rate of lacking physiological hypermetropia, between the experimental group and the control group children.?RESULTS:One school year later,the rate of low vision, rate of referral caused by refractive abnormality and the rate of astigmatism, were significantly lower (P<0.05)in the experimental group under the mode of“combination of medicine and education”, which were also lower than those before experiment(P<0.05).The average of the equivalent spherical lens of experimental group increased and the rate of lacking physiological hypermetropia decreased significantly, compared with the control group ( P <0.05 ) and with those before experiment(P<0.05).?CONCLUSION:Using “combination of medicine and education” eye health care model,is good for children's visual development,so as to reduce the rate of low vision and delay the occurrence of myopia.

OBJECTIVETo assess the outcome of orthodontic treatment with upper jaw or upper and lower jaw extraction for Class II division 1 malocclusion using the peer assessment rating (PAR) index.

METHODS28 patients with Class II division 1 were extracted two first premolars or second premolars of upper jaw, and 24 patients were extracted four premolars of upper and lower jaw N. The PAR was applied on pre-and post-orthodontic treatment dental casts for the fifty-two cases.

RESULTSThe upper and lower jaw extraction groups had significantly higher initial PAR scores and the weighted PAR total scores (P<0.05). Although significantly different before treatment, both groups were not statistically different after treatment (P>0.05).

CONCLUSIONThe upper and lower jaw extraction cases showed more severe dental displacement. Both treatment can acquire successful results.

Bicuspid ; Female ; Humans ; Male ; Malocclusion ; Malocclusion, Angle Class II ; Mandible ; Maxilla ; Orthodontics, Corrective ; Tooth Extraction