Poly adenosine diphosphate ribose polymerase (PARP) inhibitors lead to synthetic lethality in homologous recombination repair-deficient (HRD) tumors by inhibiting DNA damage repair. Two PARP inhibitors, olaparib and talazoparib, have been approved for the salvage treatment of breast cancer susceptibility gene (BRCA) mutation, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer, and adjuvant treatment of early breast cancer. PAPR inhibitor single agent shows good antitumor activity and controllable safety. A number of clinical studies on PAPR inhibitors combined with chemotherapy, radiotherapy, antiangiogenic therapy and immunotherapy are being carried out. The indications of PARP inhibitors also extend from BRCA mutation to HRD, from ovarian cancer and breast cancer to other solid tumors, promising to benefit more patients in the future.

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/drug therapy* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Receptor, ErbB-2

The increasing atmospheric carbon dioxide levels have been correlated with global warming. Carbonic anhydrases (CA) are the fastest among the known enzymes to improve carbon capture. The capture of carbon dioxide needs high temperature and alkaline condition, which is necessary for CaCO₃ precipitation in the mineralization process. In order to use CAs for biomimetic carbon sequestration, thermo-alkali-stable CAs are, therefore, essential, and polyextremophilic microbes are one of the important sources of these enzymes. The current review focuses on both those isolated by thermophilic organisms from the extreme environments and those obtained by protein engineering techniques, and the industrial application of the immobilized CAs is also briefly addressed. To reduce the greenhouse effect and delay global warming, we think further research efforts should be devoted to broadening the scope of searching for carbonic anhydrase, modifying the technology of protein engineering and developing highly efficient immobilization strategies.
Biomimetics ; Carbon Dioxide ; Carbon Sequestration ; Carbonic Anhydrases ; Protein Engineering

Objective To optimize the HT22 cell oxygen-glucose deprivation/re-oxygenation models in hippocampal neurons of mice,discuss the basis of model establishment and test the related parameters.Methods HT22 cell growth curve was plotted by cell counting and cell doubling time was calculated,and then,the oxygen-glucose deprivation time and re-oxygenation time were determined by LDH assay.The CCK-8 assay,cell counting,cell morphology and flow cytometry were performed to further optimize the parameters of the models.Results The HT22 cell doubling time was 17 h 18 min.The oxygen-glucose deprivation time was 18 h and the re-oxygenation was 20 h.CCK-8 assay indicated that absorbance in cells of oxygen-glucose deprivation 18 h/re-oxygenation 20 h (OGD 18 h/R20 h) group was 0.334±0.138,which was significantly lower than that in the control group (0.756±0.026,P＜0.05);cells in the OGD18 b./R20 h group were shrank obviously.Flow cytometry indicated that the percentage of cells in terminal apoptosis or non-viable non-apoptotic cells was 24.56％±5.76％ and that of viable apoptotic cells was 2.63％±0.55％ in the OGD18 h/R20 h group,which were significantly higher than those in the control group,respectively (8.13％±0.87％ and 0.80％±0.10％,/P＜0.05).Conclusion The HT22 cell oxygen-glucose deprivation/re-oxygenation models are successfully established;both oxygen-glucose deprivation time and re-oxygenation time are related to the cell doubling time,and OGD18 h/R20 h can preferably help the establishment;.

Objective To explore the change of proportion of peripheral blood dendritic cells (DCs) in patients with stroke. Methods 56 patients (30 cases of cerebral infarction and 26 cases of cerebral hemorrhage) in Beijing Bo'ai hospital from June to September, 2014 and 14 healthy controls were investigated. The severity of stroke was assessed with the National Institutes of Health Stroke Scale (NIHSS). Flow cy-tometry analysis was employed to detect the proportion of DCs subtypes in the peripheral blood. Results No obvious difference was found in DCs between the stroke patients and the controls. Compared to the control group, the percentages of peripheral blood myeloid dendritic cells (mDCs) decreased in the cerebral hemorrhage and the cerebral infarction subgroups (P<0.001). The percentages of plasmacytoid den-dritic cells (pDCs) reduced significantly in the cerebral hemorrhage and the cerebral infarction subgroups (P<0.05). The stroke patients were divided into NIHSS≤7 subgroup and NIHSS>7 subgroup. The percentages of pDCs in the cerebral hemorrhage and the cerebral infarction patients were significantly lower in the NIHSS>7 subgroup than in the NIHSS≤7 subgroup (P<0.05). While there was no statistical differ-ence between NIHSS≤7 subgroups and NIHSS>7 subgroups in the percentages of mDCs in the cerebral hemorrhage and cerebral infarction patients. Conclusion The proportion of DCs subtypes in the peripheral blood in stroke patients changed significantly, indicating inflamma-tion responds play a role in stroke.

Objective To investigate types of knee joint injury among island garrison force and the effect of arthroscopy,and also to recommend related preventive measures.Methods Forty-two cases of knee joint injury were collected from the medical data registered from March,2012 to April,2013,and diagnosis and treatment were performed by arthroscopy.Results Of the 42 cases of knee joint injury,there were 31 cases of anterior cruciate ligament injury,14 cases of internal meniscus injury combined with external meniscus injury,2 cases of simple meniscus injury,1 case of external discoid cartilage injury,2 cases of chondromalacia patellae,3 cases of traumatic synovitis,1 case of posterior cruciate ligament injury,and 1 case of traumatic knee joint arthritis.Following treatment by arthroscopy,all the patients returned to duty.Conclusion In the knee joint injury that occurred among island garrison military per-sonnel,the highest incidence was anterior cruciate ligament injury,with complete rupture of ligament in most cases.There was a rela-tively high rate of misdiagnosis and treatment delay.For this reason,attention should be paid to knee joint injury occurred among mili-tary personnel,and early arthroscopy should be performed as early as possible,so as to improve cure rate.

Objective To investigate types of knee joint injury among island garrison force and the effect of arthroscopy,and also to recommend related preventive measures.Methods Forty-two cases of knee joint injury were collected from the medical data registered from March,2012 to April,2013,and diagnosis and treatment were performed by arthroscopy.Results Of the 42 cases of knee joint injury,there were 31 cases of anterior cruciate ligament injury,14 cases of internal meniscus injury combined with external meniscus injury,2 cases of simple meniscus injury,1 case of external discoid cartilage injury,2 cases of chondromalacia patellae,3 cases of traumatic synovitis,1 case of posterior cruciate ligament injury,and 1 case of traumatic knee joint arthritis.Following treatment by arthroscopy,all the patients returned to duty.Conclusion In the knee joint injury that occurred among island garrison military per-sonnel,the highest incidence was anterior cruciate ligament injury,with complete rupture of ligament in most cases.There was a rela-tively high rate of misdiagnosis and treatment delay.For this reason,attention should be paid to knee joint injury occurred among mili-tary personnel,and early arthroscopy should be performed as early as possible,so as to improve cure rate.

Objective To investigate the clinicopathological characteristics and prognostic factors of hepatolithiasis associated with intrahepatic cholangiocarcinoma (HLAIHCC).Method A ret rospective study was conducted on 36 patients who suffered from histopathologically confirmed HLAIHCC.These patients received surgical resection of the tumor from June 2006 to September 2009.Results The overall 1,3,5 year survival rates for patients with HLAIHCC were not significantly better than those patients with ICC (63.6％,36.4％,and 30.3i％ vs.65.4％,34.3％,and 28.6％,P=0.57).For the patients who received curative resection,the 1-,3-,and 5-year survival rates (81.4 ％,61.7 ％,and 58.6 ％) were significantly better than those who received palliative resections (x2 =20.426,P＜0.001).The white blood cell count was significantly higher in the HLAIHCC group than in the ICC group (x2 =19.70,P＜0.001) and tumor size was significantly smaller in the ICC group than in the HLAIHCC group (P=0.04).Serum CA19-9 level (P=0.049) and resection margin (P=0.019) were independent risk factors of prognosis.Conclusions This study showed HLAIHCC to have different clinicopathological characteristics from ICC.Curative resection was the optimal surgical treatment for HLAIHCC.Serum CA19-9 level and resection margin were independent risk factors of prognosis.

Objective To investigate the role and mechanism of low-dose aspirin concurrent with IFN-a in inducing hepatocellular carcinoma apoptosis in BEL-7402 cells. Methods BEL-7402 cells were cultured and treated with IFN-α,or low dose aspirin or both.MTT and flow cytometry were used to measure the cell proliferation and apoptosis after treatment with a singular drug or the combined regiment.The expressions of the apoptosis-related proteins were detected by Western blot.Results MTT assay revealed after IFN α administration alone or combined with aspirin treatment for 48 h,the proliferation ratio of the IFN-α or aspirin group were 82.45％ ± 1.71％ and 83.22％ ±2.26 ％,compared with the control group.The group which received the combined therapy had a proliferation ratio of 69.84 ％ ±1.18 ％,which was significantly lower than the single groups (P＜0.05).The flow cytometry revealed that the apoptosis ratio in IFN-α group and aspirin group were 14.78 ％ ±1.93％ and 14.00％±0.61％,respectively,while the IFN-α + aspirin group was 21.68％±1.28％,which was also significantly higher than that of the single groups (P＜0.05).Western blot detected that IFN-α and aspirin (1 mmol/L) could promote caspase-3 and caspase-9 protein expressions,and when the two drugs were combined,caspase-3 and caspase-9 were also significantly activated.IFN-α alone or combined with aspirin can promote the expression of pro-apoptotic protein Bax (P＜0.05),while the anti-apoptotic proteins expression of Bcl-2 and Bcl-xl did not change significantly (P＞0.05).Conclusions Low-dose aspirin can cooperate with IFN-α in inhibiting the BEL-7402 cell growth and inducing the cell apoptosis by activating and increasing caspase-3 and caspase-9 levels,which may be related to the increased expression of pro-apoptotic protein Bax.

Objective To evaluate the efficacy of early intervention of tendon technique combined with physical therapy on patients afterlumbar disc herniation (LDH) surgery in functional recovery. Methods 44 patients after LDH surgery were randomly divided into interventiongroup (n=20) and control group (n=24). They were accessed by Japanese Orthopaedic Association score (JOA score), Oswestry DisabilityIndex (ODI) and electromyogram (EMG) before surgery, 2 weeks and 3 months after surgery. Results The scores of JOA and ODIwere better in intervention group than in the control group (P<0.05) 2 weeks and 3 months after surgery. There was no significant differencebetween 2 groups in latency, amplitude, nerve conduction velocity during the same period (P>0.05). The absolute value added of motornerve conduction velocity 3 months after surgery was higher in the intervention group than in the control group. Conclusion Early interventionof tendon technique combined with physical therapy on patients after LDH surgery has positive effect in functional recovery, and wasuseful in promoting recovery of neurological function.