Breast cancer is the principal cause of death in malig-nancy women , usually treated with the combination of surgery , chemotherapy , radiotherapy and endocrinotherapy .With the de-velopment of cell biology , molecular biology , immunology, im-munotherapy becomes a new field of breast cancer treatment .In this review, we discuss new findings in breast cancer immuno-therapy , including recent successes with bispecific antibodies and immune checkpoint blockade .We also discuss therapeutic cancer vaccines and highlight several additional immunotherapy modalities in early stages of development .

Objective To study the role and clinical significance of chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF) in the occurrence and development of renal cell carcinoma. Methods Expression of CXCR4 and VEGF were detected by SP immunohistochemical technique in 56 cases of kidney carcinoma tissues (including 20 cases of lymph node metastasis), 10 normal tissues nearby kidney cancer. Results The positive rates of CXCR4 and VEGF were 66. 1% (37/56) and 73. 2% (41/56),which were significantly higher than those in normal tissues( 20. 0% (2/10) and 30. 0% (3/10), respectively) (P ＜ 0. 05 ＝. The expression of CXCR4 protein was significantly positively correlated with that of VEGF protein (r = 0. 315 ,P ＜ 0.05 ＝ in renal cell carcinoma. The expression of CXCR4 and VEGF was closely related to stages of tumor ( χ2 = 9. 520, P = 0. 023; χ2 = 9. 072, P = 0. 027 ), lymphatic metastasis, degree of invasion ( χ2 =4. 972, P = 0. 026; χ2 = 3.910, P = 0. 034 ), and microvessel density ( MVD) ( P ＜ 0. 05 ＝. However, they were not related to sex ( χ2 = 0. 020, P= 0. 887; χ2 = 0. 001, P = 0. 716 ), tumor size ( χ2 = 0. 003, P = 0. 995; χ2 =0. 108, P = 0. 990) and pathologic types ( χ2 = 1. 960, P = 0. 900; χ2 = 0. 112, P = 0. 994). Conclusion There is a significant positive correlation between high expressions of CXCR4 and VEGF proteins in renal cell carcinoma,the high expressions of CXCR4 and VEGF proteins may be related to the metastasis and prognosis of renal cell carcinoma,thus they could be used as important indicators in judging the metastasis prognosis of renal cell carcinoma,and offer prospects for the treatment of renal cell carcinona.

OBJECTIVE:To investigate the effects of Astragalus injection combined with Salmeterol propionate powder inhala-tion on pulmonary function,cytokines and blood rheology indexes of Chronic obsrnctine pulmonary disease (COPD) patients. METHODS:104 COPD patients were divided into observation group and control group according to the randorn number table meth-od,with 52 cases in each group. Control group was given routine symptomatic treatment+Salmeterol propionate powder inhalation 1 dose,bid;observation group was additionally given Astragalus injection 30 ml added into 5% Glucose injection 250 ml,ivgtt, qd,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Clinical efficacy,pulmonary function indexes [forced expiratory volume in one second(FEV1),forced vital capacity(FVC),FEV1/FVC],CRP,cytokine [IL-6,IL-8,TNF-α] levels,blood rheology indexes (whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,hematokrit and plasma viscosity),and the occurrence of ADR were observed in 2 groups. RESULTS:The total effective rate of observation group (94.23%)was significantly higher than that of control group(75.00%);compared with before treatment,FEV1,FVC and FEV1/FVC of 2 groups were significantly increased after treatment,and those of observation group were significantly higher than those of control group;CRP,IL-6,IL-8 and TNF-α of 2 groups were significantly decreased,and those of observation group were signifi-cantly lower than those of control group. The whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,hema-tocrit and plasma viscosity of observation group were decreased significantly after treatment,and the observation group was signifi-cantly lower than the control group,with statistical significance(P<0.05). No significant ADR was found in 2 groups. CONCLU-SIONS:Astragalus injection combined with Salmeterol propionate powder inhalation is significantly effective for COPD,improves pulmonary function of patients,improves micro inflammatory state and decreases blood rheology indexes with good safety.

Objective To investigate the effects of intrathecal injection of α-cyano-4-hydroxy-cinnamate (4-CIN) in rats with neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI).Methods Eighteen male SD rats were divided randomly into 3 groups(n=6):sham group (group S),CCI model group (group C0) and 4-CIN group (group C1).Group C0 and C1 were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve ; and group S were treated as sham operated rats.Two days after operation,group C1 received intrathecal injection of 100 μmol 4-CIN dissolved in 10％ DMSO 10 μl,while group C0 received intrathecal injection of 10％ DMSO 10 μl only.The paw withdrawal thermal latency(PWTL) and paw withdrawal mechanical threshold(PWMT) were tested 1 d before operation and 1 d,3 d,7 d,10 d,14 d after operation(T0-5).Results The basic values of PWMT and PWTL before operation showed no statistically significant differences among the three groups.On T1-5,the PWMT((11.71 ±2.81) g,(9.76± 1.00) g,(8.22± 1.33) g,(6.50± 1.48) g,(4.67± 1.03) g) and PWTL((11.36±2.18) s,(11.60±2.54) s,(8.54± 1.42) s,(7.59± 1.00) s,(6.88± 0.42) s) in group C0 were significantly lower than those in group S (P＜0.05).However,there were no significant differences between group S and C1 on T2-5(P＞0.05).Conclusion Intrathecal administration of 4-CIN can attenuate neuropathic pain in rats induced by CCI.

Objective: To explore the effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury of rats caused by excessive fluoride intake. Methods: All 40 Wistar rats were randomly divided into four groups, control group, low fluoride group, medium fluoride group and high fluoride group. The rats in control group were fed with tap water (fluoride concentration=0.344 mg/L) and the experimental rats were fed with the water contaminated fluoride with the dose of 5, 10 and 20 mg/L. 10 rats (female: male=1∶1) in each group were sacrificed after 8 months of exposure through drinking water. The contents of urine fluoride were detected by fluorine ion selective electrode method. Morphology of thyroid was observed through light microscope and apoptosis in thyroid were detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were analyzed by RT-PCR and immunohistochemistry respectively, and results were compared among groups. Results: The contents of urine fluoride in all fluoride treated groups were separately (4.74±1.88), (7.70±2.82) and (10.50±2.92) mg/L, which were gradually higher than that of control group (2.23±0.54) mg/L (P<0.05). Morphological changes were found in thyroid tissues of fluoride treated groups, thyroid follicular hyperplasia or even no cavity cell clusters were observed. Apoptosis in thyroid were notably increased in fluoride treated groups. The mRNA expression levels of GRP78 in all fluoride treated groups were separately 1.30±0.42, 1.39±0.29 and 1.50±0.27, which were significantly higher than that of control group (0.93±0.24) (P<0.05). And the mRNA expression levels of CHOP in medium and high fluoride groups were separately 1.17±0.29 and 1.30±0.26, which were significantly higher than that of control group (0.91±0.20) (P<0.05). The protein expression levels of GRP78 and CHOP in medium and high fluoride groups were respectively 29.68±4.04, 29.90±3.74 and 4.05±1.62, 4.44±1.81, which were significantly higher than those in the control group (separately 23.80±6.36, 2.27±0.89) (P<0.05). Conclusion Excessive-fluoride intake can induce thyroid injury, and endoplasmic reticulum stress-induced apoptosis might be involved in the injury.

Objective To evaluate the role of neuron-restrictive silencer factor (NRSF) in the spinal cord in remifentanil-induced hyperalgesia in a mouse model of incisional pain (IP) .Methods Fifty-six male Kunming mice were randomly divided into 7 groups (n=8 each):control group (group C) ,IP group (group I) ,IP +remifentanil group (group IR ) , NRSF antisense oligonucleotide group (NAS group ) , IP + NRSF antisense oligonucleotide group (I+NAS group ) ,IP + remifentanil + NRSF mismatch oligonucleotide group (IR+NMS group) , and IP + remifentanil + NRSF antisense oligonucleotide group (IR + NAS group ) . Artificial cerebrospinal fluid 5 μl was injected intrathecally once a day for 3 consecutive days in C ,I and IR groups .NRSF antisense oligonucleotide NAS 10μg was injected intrathecally once a day for 3 consecutive days in NAS ,I+NAS and IR + NAS groups . NRSF mismatch oligonucleotide 10 μg was injected intrathecally once a day for 3 consecutive days in IR+NMS group .A 1-cm longitudinal incision was made through skin ,fascia and muscle of the plantar aspect of the right hindpaw to establish the model of incisional pain in sevoflurane-anesthetized rats .At 30 min after the last injection ,normal saline 0.4 ml was infused subcutaneously in C and NAS groups ,the model was established and normal saline 0.4 ml was subcutaneously infused simultaneously in I and I+NAS groups ,and the model was established and remifentanil 0.04 mg/kg was subcutaneously infused simultaneously in IR ,IR+NMS and IR+NAS groups .At 3 days before operation (T0 ) ,4 h before operation (T1 ) and 4 ,12 ,24 and 48 h after operation (T1-5 ) ,mechanical paw withdrawal threshold to von Frey stimuli (PMWT ) and paw withdrawal latency to thermal nociceptive stimulus (PTWL ) were measured .Results Compared with C group ,the PWMT and PWTL were significantly decreased at T2-5 in I ,IR ,I+NAS ,IR+NMS and IR+NAS groups ( P<0.05) ,and no significant change was found in the PWMT and PWTL at each time point in NAS group ( P>0.05 ) .Compared with I group ,the PWMT and PWTL were significantly decreased at T2-5 in IR and IR+NMS groups ( P<0.05) , and no significant change was found in the PWMT and PWTL at each time point in I +NAS group ( P>0.05) . Compared with IR group ,no significant change was found in the PWMT and PWTL at each time point in IR+NMS group ( P>0.05) ,and the PWMT and PWTL were significantly increased at T2-5 in IR+NAS group ( P<0.05) . Conclusion NRSF in the spinal cord is involved in the development and maintenance of hyperalgesia induced by remifentanil in a mouse model of IP .

Objective To study the utility of fibrin glue on prevention of bleeding after endoscopic submucosal dissection ( ESD).Methods Consecutive patients with gastrointestinal tumors who underwent ESD between July 2015 and June 2016 in the First Affiliated Hospital of Nanjing Medical University were enrolled in the study. The patients receiving ESD before December 31, 2015 were assigned into the fibrin glue group, and patients receiving ESD after December 31, 2015 were assigned into the control group. The fibrin glue group was sprayed with fibrin glue on wound followed by routine hemostasis method, and the control group was given routine hemostasis method only. The bleeding rate after ESD, mean hospital stays and cost were compared between the two groups.Results The bleeding rate after ESD in the fibrin glue group was significantly lower than that in the control group[7. 45%(12/161) VS 14. 79%(25/169), P＝0. 035]. There was no significantly difference in the mean hospital stays (9. 09±2. 65 days VS 9. 20±2. 99 days, P＝0. 744) and mean cost (24 246±5 519 yuan VS 25 214±6 258 yuan, P＝0. 138) between the two groups.Multivariate analysis revealed that the use of fibrin glue was a protective factor for bleeding after ESD. Conclusion Fibrin glue is safe, effective and economical in prevention of bleeding after ESD.

Objective:To evaluate the efficacy and prognosis of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (EGC).Methods:Data of 393 patients with 400 EGC lesions who underwent ESD between January 2010 and April 2019 in the First Affiliated Hospital of Nanjing Medical University were collected in the retrospective study. Patients were divided into undifferentiated-type group (50 cases with 50 lesions) and differentiated-type group (343 cases with 350 lesions) according to postoperative pathology. Their data including age, gender, size and location of the resected lesion, general classification, depth of infiltration, presence or absence of ulcers, and follow-up were compared.Results:Logistic regression analysis showed that age ≤60 years ( OR=2.02, 95% CI: 1.04-3.95, P=0.011), female ( OR=2.83, 95% CI: 1.41-5.68, P=0.003), gastric antrum lesions ( OR=3.92, 95% CI: 1.65-9.30, P=0.002), endoscopic depressed type ( OR=5.37, 95% CI: 2.16-13.38, P<0.001), and submucosa invasive depth ( OR=5.09, 95% CI: 2.40-10.80, P<0.001) were independent risk factors for undifferentiated EGC. The undifferentiated-type group showed a significantly higher non-curative resection rate [90.0% (45/50) VS 19.8% (68/343), χ2=104.902, P<0.001]. Of the 393 patients, 5(4.4%) died in the 113 patients with non-curative resection, while 2 (0.7%) died in the 280 patients with curative resection. Patients with non-curative resection had a higher mortality ( χ2=5.558, P=0.023). There were 27 and 51 patients undergoing additional surgery in the undifferentiated-type group and the differentiated-type group, respectively. None of them had recurrence. Among the 315 patients who did not undergo surgery, the recurrence rate of the undifferentiated-type group was significantly higher than that of the differentiated-type group [26.1% (6/23) VS 4.1% (12/292), χ2=5.560, P<0.001]. Conclusion:Young age (≤60 years), female, gastric antrum lesions, endoscopic depressed type, and submucosa invasive depth are predictors of undifferentiated EGC. Patients with undifferentiated EGC have a higher non-curative resection rate and higher possibility of recurrence after ESD, and additional operation are suggested.

OBJECTIVE: To determine the changes of Mu-opioid receptor (Mor) and neuron-restrictive silencer factor (NRSF) in periaquductal gray (PAG) in mouse models of remifentanil-induced postoperative hyperalgesia. METHODS: Thirty-two Kun-Ming mice were randomly divided into 4 groups (8 mice in each group): Group C (mice underwent a sham procedure and saline was infused subcutaneously over a period of 30 min), Group I (mice underwent a surgical incision and the same volume of saline), Group R (mice underwent a sham procedure and remifentanil was infused subcutaneously at the moment of surgical incision over a period of 30 min), and group IR (mice underwent a surgical incision and remifentanil). Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) tests were performed 24 h before the operation and 2, 6, 24, and 48 h after the operation. The specimens were collected after behavioral testings at 48 h. The expressions of Mor and NRSF in mice's PAG neurons were determined by Western blot. RESULTS: Mechanical allodynia and thermal hyperalgesia developed in Group I, R and IR (P<0.01). Intraoperative infusion of remifentanil enhanced mechanical allodynia and thermal hyperalgesia in mice with planta incision (P<0.01). In Group R and Group IR, the expression of Mor was significantly lower (P<0.01) and NRSF was significantly higher (P<0.01) when compared with Group C and Group I. CONCLUSION Intraoperative infusion of remifentanil induces postoperative hyperalgesia in mouse models, accompanied with decreased expressions of Mor and increased of NRSF level in PAG neurons, which may be involved in remifentanil induced hyperalgesia.
Animals ; Disease Models, Animal ; Hyperalgesia ; chemically induced ; Mice ; Pain, Postoperative ; Periaqueductal Gray ; drug effects ; metabolism ; Piperidines ; administration & dosage ; Receptors, Opioid, mu ; metabolism ; Remifentanil ; Repressor Proteins ; metabolism

【Objective】 To analyze and mine the prescription rules of traditional Chinese medicine enema treatment of chronic kidney disease （CKD） in CNKI platform journals based on data mining and network pharmacology so as to find high-frequency core Chinese medicines and predict the potential targets of core Chinese medicines and explore the mechanism of action of core Chinese medicines in the treatment of CKD. 【Methods】 Taking CNKI as the data source， we retrieved the clinical literature of traditional Chinese medicine enema in the treatment of CKD. SPSS modeler 18.0 statistical software was used for statistical processing and association rule analysis. IBM SPSS statistics 21 statistical software was used for cluster analysis. BATMAN-TCM and TCMSP were used to retrieve the effective components and related targets of drugs. Genecards， OMIN， Drugbank， DisGenet， TTD， and PharmGkb databases were used to retrieve disease-related targets， and Venny platform was used to screen disease and drug intersection targets. We used STRING database to obtain relevant documents， Cytoscape 3.8.2 software for visual analysis， Metascape database for enrichment analysis， Wechat website to draw bubble diagram， and AutoDockTools-1.5.6 software for molecular docking prediction. 【Results】 We selected 276 effective prescriptions involving 120 traditional Chinese medicines. The frequency of 19 traditional Chinese medicines was more than 10. Totally 18 core drug combinations were obtained. Cluster analysis could be divided into four categories. The visual net-work analysis shows that “rhubarb， dandelion， oyster， Salvia miltiorrhiza and aconite” are highly correlated and occupy the core position. Through the prediction of the potential targets of five core drugs， 659 “drug disease” intersection targets and 173 core targets were obtained， of which “MAPK1， AKT1 and STAT3” are the key targets， “progesterone， neocryptotanshinone Ⅱ and emodin”. It is predicted that it may play a role in “PI3K Akt signal pathway， MAPK signal pathway， JAK-STAT signal pathway”. Molecular docking showed that the key components have good binding activity with key targets. 【Conclusion】 Based on data mining and network pharmacology， traditional Chinese medicine enema treatment of CKD mainly uses rhubarb as the main drug， assisting warming yang to remove blood stasis and turbidity relief drugs. The key components of its core drug can act on PI3K-Akt by regulating key targets such as PIK3R1. Signal pathways and other pathways play a role in providing new ideas for the treatment of this disease with traditional Chinese medicine enema， medication strategies for clinical prescriptions， and a basis for follow-up further research.