Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

With the development of more and more multi-center and cross-field cooperative medical research,the establishment of high-quality and efficient ethical collaborative review and mutual recognition systems is an inevitable demand for multi-institutional research,and an inevitable move to implement relevant national policies.Based on the work practice of ethical collaborative review and mutual recognition in Shenzhen,by analyzing the practical challenges of ethical collaborative review and mutual recognition in China,this paper proposed that to ensure the homogeneity and efficiency of review.Government departments need to take the lead,establish an ethical review alliance,and clarify responsibilities and rights.Based on actual needs,system first,and effective communication,ethical collaborative review and mutual recognition of results could be jointly promoted,aiming to provide a reference for our counterparts in China to promote ethical collaborative review and mutual recognition of cross-institutional research.

OBJECTIVES: To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats. METHODS: Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues. RESULTS: Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05). CONCLUSIONS Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.
Rats ; Male ; Animals ; NF-kappa B/metabolism* ; Rats, Sprague-Dawley ; Glucose ; Lipid Metabolism ; Toll-Like Receptor 4 ; Cholesterol, LDL/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Medicine, Chinese Traditional ; Signal Transduction ; Triglycerides ; Transcription Factors/metabolism* ; Obesity ; RNA, Messenger

Objective To investigate the relation between the characteristics of CD8+T lymphocyte infiltration and the prognosis of triple-negative breast cancer patients. Methods We retrospectively analyzed the clinicopathological data of 126 patients with triple-negative breast cancer undergoing preoperative neoadjuvant chemotherapy. Immunohistochemical staining was used to analyze the relation between CD8+T lymphocyte infiltration and clinicopathological characteristics. Kaplan-Meier method was used to draw the survival curve, and Cox risk ratio regression model was used to analyze the prognostic factors affecting disease-free survival time (DFS). Results High-density CD8+Tils was associated with age < 60 years old, high pathological grade and high clinical stage (P < 0.05). The pCR rate of high-density CD8+Tils group was higher than that of the low-density group (66.7% vs. 19.8%, P=0.000). The median DFS of the high-density group was significantly longer than that of the low-density group (49 vs. 25 months, P < 0.05). Multivariate analysis showed that high pathological grade, tumor diameter > 2 cm, lymph node metastasis, vascular invasion and CD8+Tils low-density infiltration were factors for poor prognosis (P < 0.05), and CD8+Tils was an independent prognostic factor. Conclusion CD8+Tils may be an independent prognostic indicator for triple-negative breast cancer. The patients with high-density infiltration have high postoperative pCR rate, long DFS and better long-term efficacy.

Objective To explore the clinical significance of the ratio of descending aorta diameter to ascending aorta diameter (rDA) in rapid diagnosis of Stanford B aortic dissection (AD). Methods A total of 118 patients with chest pain admitted to the emergency department from January 2013 to June 2018 in the People′s Hospital of Longhua were selected,and 42 patients with Stanford B type AD (group A) and 76 patients without AD (group B) were diagnosed by CT angiography.Eighty healthy people in the same period were selected as control group (group C). The descending aorta diameter and ascending aorta diameter were measured and rDA was calculated. The receiver operating characteristic curves were made. The sensitivity and specificity of descending aorta diameter and rDA for predicting Stanford B-type AD were analyzed. Results The descending aorta diameter, ascending aorta diameter and rDA in group A (male and female) were significantly higher than those in group C (male and female), while the descending aorta diameter and rDA in group A (male and female) were significantly higher than those in group B (male and female) (P<0.05). The sensitivity and specificity of descending aorta diameter with 30.0 mm as the cut-off point for the diagnosis of Stanford B-type AD were 92.9%(39/42),82.9%(63/76), and those of rDA with 0.8 as the cut-off point for Stanford B-type AD were 95.2%(40/42),90.8%(69/76). Conclusions The descending aorta diameter and rDA can be used as indicators for rapid diagnosis of Stanford B-type AD, and rDA is better than the diameter of descending aorta.

Objective To analyze the existence of zero cited papers in Chinese Journal of Endemiology,find problems,and to improve the citation frequency and academic influence of the journal.Methods In Wanfang Data Knowledge Service Platform,the papers published in Chinese Journal of Endemiology from 2013 to 2015 were accurately retrieved.The papers were sorted according to the frequency of citations from high to low,and zero cited papers were selected.Publication time,publication column,download frequency and other information of the paper were recorded,and statistical analysis was performed.Search time was up to October 24,2018.Results From 2013 to 2015,a total of 680 papers were published,147 papers were zero cited papers,and the rate of zero cited papers was 21.62％.Among them,28,33 and 86 papers were zero cited papers in 2013,2014 and 2015,and the rates of zero cited papers were 13.33％ (28/210),15.64％ (33/211) and 33.20％ (86/259),respectively,the difference was statistically significant (x2 =33.477,P ＜ 0.01).The rates of zero cited papers in the columns of Editorial,Health Education,and Experts Forum were lower,which were 5.56％ (1/18),7.14％ (1/14) and 9.52％ (2/21),respectively;and the rates of zero cited papers in the column of Method and Brief Report were higher,which were 36.36％ (8/22) and 32.93％ (27/82),respectively.The average download frequency of 147 zero cited papers was 36,ranging from 0 to 151 times.Conclusions The citation frequency of a paper is related to the time of publication.The longer the time is,the lower rate of zero cited paper is.The journal can appropriately increase the proportion of commentary articles;publish more practical methods,and brief reports to enhance the citation frequency and academic quality.

Objective To primarily explore the efficacy,onset time and safety of low frequency repetitive transcranial magnetic stimulation (rTMS) over the left orbitofrontal cortex (LOFC) on obsessive-compulsive disorder(OCD).Methods Twenty-four OCD patients were randomly assigned into 2 groups,one group (n＝12) with sertraline and rTMS,the other group (n＝12) with sertraline and sham rTMS.The stimulus parameter was 80～-110～ motor threshold,1 Hz,5 sessions per week.The efficacy was assessed by using Y-BOCS,HAMD and HAMA at base line,2,4 and 6th week after treatment,and the safety by recording Adverse Event and Severe Adverse Event.Results The scores of Y-BOCS(F＝23.401,P＜0.01),obsession(F＝23.516,P＜0.01),compulsion (F＝15.025,P＜0.01),HAMD (F＝7.23,P＜0.01) and HAMA (F＝8.389,P＝0.002) of 2 groups all significantly decreased after 6 week treatment,but there was no significant differences between 2 groups.The effective rate of the two groups was statictically different (Fisher test,P＝0.030),and the remission rate was not statistically different (Fisher test,P＝0.183).The Y-BOCS scores in the sertraline + rTMS group at 2 week treatment (23.0 ± 5.1 vs.18.1 ± 5.7) were statistically different from the baseline(LSD test,P＝0.005),but the sertraline + sham rTMS group did not show a statistically significant difference(LSD test,P＝0.025) until 4 weeks after treatment (24.4±4.3 vs.17.6±7.3).The occurrence rates of adverse events were not statistically different among 2 group (all P＞0.05).No severe adverse events happened.Conclusions Low frequency rTMS over the LOFC combined drug may have potential advantages in OCD with faster effect than drug.But the finding needs to be verified in large sample with randomized controlled trials.

Objective To primarily explore the efficacy,onset time and safety of low frequency repetitive transcranial magnetic stimulation (rTMS) over the left orbitofrontal cortex (LOFC) on obsessive-compulsive disorder(OCD).Methods Twenty-four OCD patients were randomly assigned into 2 groups,one group (n＝12) with sertraline and rTMS,the other group (n＝12) with sertraline and sham rTMS.The stimulus parameter was 80～-110～ motor threshold,1 Hz,5 sessions per week.The efficacy was assessed by using Y-BOCS,HAMD and HAMA at base line,2,4 and 6th week after treatment,and the safety by recording Adverse Event and Severe Adverse Event.Results The scores of Y-BOCS(F＝23.401,P＜0.01),obsession(F＝23.516,P＜0.01),compulsion (F＝15.025,P＜0.01),HAMD (F＝7.23,P＜0.01) and HAMA (F＝8.389,P＝0.002) of 2 groups all significantly decreased after 6 week treatment,but there was no significant differences between 2 groups.The effective rate of the two groups was statictically different (Fisher test,P＝0.030),and the remission rate was not statistically different (Fisher test,P＝0.183).The Y-BOCS scores in the sertraline + rTMS group at 2 week treatment (23.0 ± 5.1 vs.18.1 ± 5.7) were statistically different from the baseline(LSD test,P＝0.005),but the sertraline + sham rTMS group did not show a statistically significant difference(LSD test,P＝0.025) until 4 weeks after treatment (24.4±4.3 vs.17.6±7.3).The occurrence rates of adverse events were not statistically different among 2 group (all P＞0.05).No severe adverse events happened.Conclusions Low frequency rTMS over the LOFC combined drug may have potential advantages in OCD with faster effect than drug.But the finding needs to be verified in large sample with randomized controlled trials.

Objective To understand the academic influence of medical statistics source journals in Heilongjiang Province from 2010 to 2015,and to provide reference for the development of periodicals.Methods Medical journals in Heilongjiang Province were selected from the "Chinese S&T Journal Citation Reports" (2011-2016),the source of literature,immediacy index,ratio of international papers,ratio of fund papers,total cited frequency,influencing factor,and he cited rate were calculated.Dynamic evaluation model was used to evaluate the academic influence,and impact assessment score (Ⅰ),relative Ⅰ (Ⅰr) and growth rate were calculated.Results A total of 11 categories of medical journals were collected,which were included in the "Chinese S&T Journal Citation Reports" from 2010-2015.There were 6 kinds of medical statistics source journals with an average annual influencing factor of ＞ 0.500:"Journal of Clinical Acupuncture and Moxibustion","Chinese Journal of Critical Care Medicine","Chinese Hospital Management","Chinese Journal of Endemiology","Information on Traditional Chinese Medicine",and "Acta Chinese Medicine and Pharmacology".The total cited frequency and the influencing factors of the six journals increased with each year.I values were 307 545.34,370 462.56,813 917.36,374 782.62,490 714.05,and 407 342.07,respectively;Irvalues were 0.67,0.80,1.77,0.81,1.06,and 0.88,respectively;growth rates were 0.87,0.41,0.14,0.63,0.06,and 0.12,respectively.Conclusion Six kinds of influential medical journals in Heilongjiang Province are in good condition,and academic influence is on the rise.

Objective To investigate the correlations among OCT4, Notch1 and DLL4 and their association with the clinicopathological features of patients with epithelial ovarian cancer (EOC). Methods A total of 207 specimens of EOC and 65 specimens of benign ovarian epithelial tumor tissues were examined for expressions of OCT4, Notch1 and DLL4 proteins using immunohistochemistry. Results The positivity rates of OCT4, Notch1 and DLL4 in EOC tissues were 60.0%, 61.8%and 60.9%, respectively, significantly higher than the rates in benign epithelial tumor tissues (9.2%, 6.2%, and 0, respectively; P<0.05). The expressions of OCT4, Notch1 and DLL4 in EOC were significantly correlated with tumor differentiation, FIGO stage, and lymph node metastasis (P<0.05). DLL4 was positively correlated with OCT4 and Notch1 expressions (r=0.758 and 0.704, respectively, P<0.001), and the latter two were also positively correlated (r=0.645, P<0.001). Overexpressions of OCT4, Notch1 and DLL4 were associated with a poor prognosis, and the survival rate was significantly lower in patients positive for OCT4, Notch1, and DLL4 than in the negative patients (P<0.05). FIGO stage and expressions of OCT4 and DLL4 were independent prognostic factors of EOC (P<0.05). Conclusion The expressions of OCT4, Notch1 and DLL4 are correlated with the differentiation, lymph node metastasis, clinical stage and prognosis of EOC. Combined detection of the 3 proteins has an important value in predicting the progression and prognosis of EOC.