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

Objective:To explore the relationship between mild cognition impairment(MCI) and components of metabolic syndrome in the elderly.Methods:A total of 293 patients aged 65 years and older with an average age of (78.8 ± 7.5) years who met the inclusion criteria were included.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate cognitive function.The components of the metabolic syndrome were compared between the MCI and the normal cognitive function(NC) groups.Binary Logistic regression analysis was used to analyze the relationship between cognitive function and components of the metabolic syndrome.Results:The levels of body mass index(BMI)and tryglicerides(TG)were lower in the MCI group than in the NC group[BMI, (22.9±3.7)kg/m 2vs.(25.3±3.3)kg/m 2, t=3.124, P=0.002; TG, 1.2±0.6 mmol/L vs. 1.4±0.7 mmol/L, t=2.615, P=0.009]. The differences in proportions of hypertension and diabetes and in levels of fasting blood glucose and high-density lipoprotein cholesterol had no statistically significance between the MCI group and the NC group(all P>0.05). Binary multivariate Logistic regression analysis showed that after adjusting for age and education, BMI was independently associated with MCI, and as BMI increased, the risk of MCI decreased( OR=0.901, 95% CI: 0.838-0.968, P=0.004). In elderly men, after adjusting for age, education level and smoking history, TG was independently associated with MCI, and as TG increased, the risk of MCI decreased( OR=0.446, 95% CI: 0.249-0.874, P=0.017). While in elderly women, no independent correlation between TG and MCI was observed. Conclusions:BMI is independently associated with MCI.Screening for cognitive function among low-level BMI elderly is helpful to identify MCI.The relationship between TG and MCI is different between different genders, and different standards might be adopted for the management of TG in elderly MCI patients with different genders.

Bone graft is an important basic condition for repairing skull defect caused by various reasons,but whether autologous bone graft or allograft bone transplantation,the clinical limitations was increasingly significant.With the development of bone tissue engineering,the introduction of bone progenitor cells and growth factors into composite scaffolds made from natural or synthetic materials,and as a substitute for bone graft has become a hot spot of research.It will review the research progress on bone graft substitute and bone biomimetic scaffold material,so as to provides reference on the further investigations.

Objective Parkinson's disease (PD) is a common degenerative disease of the central nervous system.The main pathological feature is the reduction of dopaminergic neurons,which induces motion symptoms such as resting tremor,muscle rigidity,bradykinesia,and postural disorder.The etiology and pathogenesis of PD are complex and related to a variety of factors.The current pathogenesis is related to mitochondrial dysfunction,oxidative stress,neuroinflammatory response,apoptosis,and autophagy.The early onset of PD is occult and the rate of misdiagnosis is high.It requires a new simple,safe,and effective early diagnosis method.The current methods of early diagnosis mainly include clinical non-motor symptoms,biomarkers,and imaging examination methods.

Objective To study the effects of abiotic elicitors methyl jasmonate (MeJA) and salicylic acid (SA) on the alkaloids accumulation and related enzymes metabolism inPinellia ternata suspension cell cultures. Methods Using the leaf petioles-derived suspension cell cultures as the study object, the culture duration, concentrations of MeJA and SA were determined to get the optimal alkaloids accumulation, and the activities of metabolic enzymes IMP dehydrogenase and sAMP synthase were also measured.Results A 9-fold of dried biomass and a 3-fold of alkaloids accumulation were observed inP. ternata suspension cell cultures after culture for 21 d. Both MeJA and SA could significantly promote the accumulation of alkaloids inP. ternata suspension cells. 150 μmol/L MeJA enhanced alkaloids content (4.7 mg/gDW) by 3.6 folds in comparison with control group, whereas 50 μmol/L SA showed a 2.5-fold increase. Meanwhile, 100 μmol/L MeJA and 50 μmol/L SA promoted the increase in IMP dehydrogenase activity by 3.0 and 3.7 fold respectively, and 150 μmol/L MeJA and 100 μmol/L SA showed the increase by 2.6 and 4.4 fold respectively.Conclusion Proper adding exogenous MeJA and SA can promote the accumulation of alkaloids inPinellia ternata suspension cell cultures.

Objective To investigate dynamic regulation of quantifying fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in rotational brain injury models of rabbit using diffusion tensor imaging (DTI), and its correlation with β?amyloid precursor protein (β-APP). Methods Forty-two 6-month-old New Zealand rabbits were randomly divided into three groups, including control group (n=6), mild injured group (n=18) and severe injured group (n=18), and preformed on autonomous rapidly rotational brain injury device. The rotational angles of 45° for mild injured group and 90° for severe injured group were condemned, and MRI and pathology were conducted at 6 h, 12 h, 24 h, 48 h, 72 h and 1 week after injury (3 rabbits per subgroup). Routine sequences and DTI technique were performed on 3.0 T MRI. FA and ADC values in subcortical white matter, corpus callosum and brain stem were measured. Independent t?test was performed to evaluate the significance of the intergroup difference in FA and ADC values in mild and severe injured groups of verious brain regions by timing, one?way ANOVA was performed to evaluate its timing variation and its correlation with the number of the β-APP positive axons was analyzed by Pearson correlation analysis. Results FA and ADC values of the severe injured group were lower than that of the mild in most brain regions(P<0.05), and the difference in mild injured group was smaller than that in severe injured group. Both FA and ADC values in brain stem of the severe injured group were lower at 6 h after injury compared to mild injured group, which were sensitive to injury. Furthermore, FA and ADC values in each brain regions of mild and severe injured groups showed similar dynamic trends, namely gradually decreasing by time, and FA values were more sensitive to injury than ADC values. FA values in subcortical white matter and brain stem reduced in severe injured group at 6 h after injury compared with that before injury(P<0.05), and decreased in various brain area of both injured groups at 12 h after injury(P<0.05). Meanwhile, ADC values in all regions were declined in the severe injured group at 12 h after injury(P<0.05), and decreased in various regions in both injured groups at 24—48 h after injury(P<0.05)except for subcortical white matter in mild injured group. There were statistically negative correlations between FA and ADC values and the number of β-APP positive axons in 12—48 h after injury in most regions(P<0.05). Conclusions DTI can quantitatively detect and assess the pathological process in white matter and axons of TBI in earlier stage of the brain injury, and can be applied in evaluation and quantitative diagnose in these patients.

Objective To explore the change of venous blood phase values detected by enhanced gradient echo T2 star weighted angiography(ESWAN)sequence in mild and severe traumatic brain injury (TBI) models of rabbits in diverse phases and investigate their association with neurological severity scale (NSS) scores. Methods Fifty-one New Zealand rabbits, which were randomly divided into control group (n=3) ,mild injured group (n=24) , and severe injured group (n=24) by random digital table method, underwent routine MRI and ESWAN sequence at the time points of baseline, 1 h, 6 h, 12 h, 24 h, 48 h, 72 h, 1 week, and 2 weeks after injury(3 rabbits per subgroup)respectively. Blood phase values in veins of interest were recorded. Observation of behavior characteristics and abnormalities, followed by NSS, was executed post injury, and the correlation between venous blood phase values and NSS scores was statistically analyzed. Two independent-samples t-test was applied to compare venous blood phase values of diverse measured veins in each group separately at every time ponits. One-way ANOVA was used to analyze venous blood phase values varying over time of measured vessels in each injured group. Least significant difference t-test was applied to compare blood phase values within the subgroups with each other at each time point. NSS scores of mild and severe injured groups were compared by two independent-samples t-test. Correlations between venous blood phase values and NSS scores in each vein and group was analyzed with Spearman correlation analysis. Results Blood phase values in veins of interest presented an inclination of descending, which was more obvious in severe injured groups than in the mild. Change of venous blood phase values over time featured continuing reduction in earlier phases which reached to the minimum in 24-48h, and then increased gradually, especially in VMV, VLV, DSS, and MDVB (P<0.05). ICV and DCV also showed similar trend. Values of NSS scores in the two group were (15.5 ± 3.1) and (33.2 ± 6.5) respectively (t=3.543,P=0.001). Blood phase values in most of the measured veins correlated with NSS scores (P<0.05) after 6h post injury, especially significant during 24-72h among all the measured veins(P<0.05). Higher accuracy and sensitivity were presented in the supratentorial or superficial veins compared with subtentorial or profound veins. Conclusions It is feasible to evaluate oxygen saturation of veins after TBI by measuring venous blood phase values on ESWAN images. The method is effective in the assessment of the degree of injury and clinical status, indicating a favorable application prospect.

Objective To explore the current status of job satisfaction of clinical medical staff and factors that influence the job satisfaction,and to put forward coping strategies and suggestions for improving the job satisfaction of clinical medical staff,so as to maintain workforce stability.Methods The paper will investigate the job satisfaction of clinical medical staff by sending questionnaires to all doctors and nurses working in a hospital,and use descriptive analysis and T test statistic method to analyze the current status of job satisfaction of questionnaire receivers as well as different dimensions of job satisfaction among different population groups.Results More than 85％ of questionnaire receivers think that the job they are doing is at higher risk.Over 80％ feel stressed out by their jobs.Less than 35％ are satisfied with their occupations,social status,working status,job security,and promotion opportunities.Less than 15％ feel respected by their jobs.Conclusions Generally,questionnaire receivers' job satisfaction is low.Heavy workload and poor quality of life are leading factors that contribute to their low job satisfaction.In this sense,we should adopt various measures to give attention to these key population groups.

Objective To explore the effect of QizhiJiangtang Capsule on the insulin resistance (IR)in the diabetic rats,and to clarify the action mechanism.Methods The diabetes rat models were induced by high fat diet combined with STZ injection.The successful models of the rats were randomly divided into diabetes group (DM), ShenqiJiangtang Granule group (SQ)and high (QJH),middle-(QJM),low (QJL)doses of QizhiJiangtang Capsule groups;at the same time control group (NC)was established. The drug concentrations in high, middle and low-doses of QizhiJiangtang Capsules groups were 1.35, 0.68, and 0.34 g · kg-1 respectively;and the concentration of ShenqiJiangtang Granule was 0.27 g·kg-1.After the diabetic model was established successfully, the rats were treated for 8 weeks on the basis of drug dose.Then the levels of fasting blood glucose (FBG),fasting insulin (FINS),insulin resistance index (IRI)and biochemical indexes related to lipid metabolism of the rats were measured using blood glucose detector and automatic biochemistry analyser.The gene expression of insulin receptor substrate-1 (IRS-1),phosphatidyl inositol 3-kinase (PI3K),and glucose transporter 4 (GLUT4)in liver tissue were examined by Real Time PCR.The levels of tumor necrosis factorα(TNF-α)and adiponectin (ADPN)in serum were detected using ELISA.Results Compared with control group,the levels of FBG,FINS and IRI of the rats in diabetes group were significantly increased (P<0.05 or P<0.01 );the serum total cholesterol (TC), triglyceride (TG)and low density lipoprotein (LDL)levels were significantly increased (P<0.05 ), while the serum high-density lipoprotein (HDL)level was significantly decreased (P<0.05);the mRNA expression levels of IRS-1,PI3K and GLUT4 in liver tissue were decreased (P<0.05);the level of serum TNF-αwas increased (P<0.05),but the ADPN level was decreased (P<0.05).Compared with diabetes group,the FBG level and IRI of the rats in QizhiJiangtang Capsule and ShenqiJiangtang Granule groups were significantly decreased (P<0.01);the levels of FINS of the rats middle and high doses of in QizhiJiangtang Capsule groups and ShenqiJiangtang Granule group were significantly decreased (P<0.05);the levels of serum TC,TG and LDL of the rats in middle dose of QizhiJiangtang Capsule group and ShenqiJiangtang Granule group were significantly decreased (P<0.05 or P<0.01),but the HDL level was increased (P<0.05);the mRBA expression lvels of IRS-1,PI3K and GLUT4 inliver tissue were increased (P<0.05);the levels of serum TNF-αof the rats in middle dose of QizhiJiangtang Capsule group and Shenqijiangtang Granule group were significantly decreased (P<0.05),but the serum ADPN levels were increased (P<0.05 ). Conclusion QizhiJiangtang Capsule can significantly improve the IR in the diabetic rats,and the pharmacological mechanisms are related to adapting the blood lipid component and insulin signal transduction pathways.

Objective To promote professional training aid on healthcare talents in western China,this paper aims to explore methods and to evaluate the effectiveness of a new training system for underprivileged medical professionals from hospitals of western China.Methods Questionnaires and interviews were conducted to 115 trainees and their employers took part in the Counterpart Support Project.A retrospective analysis was done to evaluate key indicators of the trainees' professional competence.Results More than 90％ of the trainees have seen great improvement on basic healthcare knowledge,clinical skills,and diagnosis and treatment practice.About 80％ the participating hospitals have enjoyed varied degrees of growth in outpatient visits,surgical volume,number of inpatient and operational efficiency.(Increase level from 0％ to 50％) Conclusions Within the frist 3 years of implementation,this new model has been proven effective to enhance participants' overall professional competence,and by tapping into the significant resource of first class hospitals,this model will help greatly promoting the development of healthcare talents in Western China.