Objective To explore the clinical significance of micro-metastasis ( mM ) in the nipple-areola complex (NAC) and the regional skin of breast cancer. Methods Samples from the skin projection of the lump and the midline-transection of the nipple-areola complex were collected from 60 breast cancer patients for both routine pathological examination ( RP) and cytokeratin-19 (CK-19) monoclonal antibody immuneohistochemical examination (IHC). Results NAC invasion was identified by RP in 3 cases (5. 0% ) , and by IHC in 7 cases (11.7%) ( x2 = 2. 25, P

objectlve To investigate the efficacy of continuous low-dose fluorouracil with cetuximab for antiangiogenic effect on colon carcinoma xenograft,and test its antitumor effect and toxicity.Methods Balb/c mice bearing CT-26 colon carcinoma xenograft were randomly divided into five groups,receiving low-dose metronomic(LDM)fluorouracil,maximum tolerated dose(MTD)fluorouracil,cetuximab,LDM fluorouracil with cetuximab therapy and saline respectively.Tumor growth,weight loss,peripheral white blood cell counts and survival of mice were monitoted.At the end of experiment,tumors were resected for tumor microvascular density(MVD)by immunofluorescence staining. Results Tumor growth inhibition was found in mice receiving LDM fluorouracil therapy and combined therapy,without significant body weight loss or leukopenia,and the survival of mice was remarkably prolonged,compared with mice receiving MTD fluorouracil or cetuximab therapy,and the antitumor effects of the combined therapy was stronger than that of the fluorouracil LDM therapy.LDM treatment and combine treatment led to statistically significant(P＜0.05)55%and 71%reduction in tumor growth,as well as 73%and 77% reduction in tumor microvessel density compared with the control respectively.Additonally,tunnel staining shows no significant difference between these treatment groups. Conclusion Continuous low-dose regimen of fluorouracil with cetuximab can significantly increase the therapeutic activity with decreased toxicity and prolonged animal survival bearing implanted colon cancer.

Objective To compraison the of exposure in the endonasal transsphenoidal approach to the sellar between microscope and endoscope. Methods Ten formalin-fixed, silicone-injected adult cadveric heads were studied. A direct endonasal transsphenoidal approach was performed via the right nostril, pushing aside the nasal septum, then reach the sphenoidal sinus. The approach was performed with the operating microscope first, then with the endoscope. For each step (sellar, suprasellar, parasellar and clival), the operative region afforded by direct microscopic view was measured and then compared with that obtained by using the edndoscope. Results It was found that the endoscope provided greater view than microscope in this approach. Although the microscope provides an adequate view of the midline structures and part of the contralateral parasellar areas; under direct endoscopic vision, the lateral extension could be widened by an additional 6.5 mm on the ipsilateral and 4 mm on the contralateral side. At suprasellar region, the microscope provides could expose the posterior part of, optic nerve and optic chiasma; but could not expose the areas anterior and superior the interspace superior the optic chiasma. Compare with the microscope, the endoscope allowed extension of bone removal and dual opening for an additional 4 mm anteriorly at the sagittal axis and an additional 3.5 mm on the ipsilateral and 4 mm on the contralateral side. At the clivus region, the medial surface of the vertical segment of the ICA and the basilar artery could be partially 7 exposed by the microscope. By the endoscope, it could gain an additional 4 mm on the ipsilateral side and 2.5 mm on the contralateral side in width. Because of the anatomical boundaries of the sphenoid sinus, the anatomincal exposure by the microscope same as the endocope at the sagittal axis. Conclusion The endoscope allows for a panoramic view and permits widening of the operative exposure in all directions. The endoscope is more suitable in the the minimal and expanded endonasal transsphenoial approach.

To analyze the molecular basis of the variation of the pathogenicity of the influenza B virus, we rescued a recombinant virus with a deletion in the carboxyl terminal of the NS1 protein using reverse genetics based on the parental virus B-S9 of B/Yamagata/16/88. A mutant strain with a deletion of 171 amino acids in the carboxyl terminal of the NS1 protein was named "B-L5". BALB/c mice were inoculated with 3 X 105 EID50 of B-L5 and the parental virus B-S9, respectively. Then, weight changes, survival, and viral titers were documented. During 3 days post-inoculation (dpi) to 7 dpi, the weight of mice infected with B-S9 decreased. However, the weight of mice infected with B-L5 showed weight decreases only at 2 dpi, and quickly recovered at 3 dpi. B-S9 and B-L5 could replicate in the lungs of BALB/c mice. However, viral titers in the lungs of mice infected with B-L5 were 7900-times lower than those of mice infected with B-S9 at 3 dpi. Viral titers in the lungs of mice infected with B-L5 were not detected at 6 dpi. These results showed that, compared with the parent virus B-S9, the mutant virus B-L5 showed lower pathogenicity in BALB/c mice. Our study suggests that deletion of the carboxyl terminal of the NS1 protein decreases the pathogenicity of the influenza B virus. Establishment of a reverse-genetics system for the B influenza virus will provide a platform for studying its pathogenesis, and mechanism of transmission, and for developing live-attenuated influenza B virus vaccines.
Animals ; Body Weight ; Dogs ; Female ; HEK293 Cells ; Humans ; Influenza B virus ; genetics ; pathogenicity ; physiology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred BALB C ; Sequence Deletion ; Survival Analysis ; Viral Load ; genetics ; Viral Nonstructural Proteins ; chemistry ; genetics ; Virulence

Objective: To report the first case of lymphomatoid gastropathy in China, and to demonstrate the clinical characteristics, diagnostic approach, treatment and prognosis in this kind of patients. Methods: One patient was diagnosed as lymphomatoid gastropathy at Peking Union Medical College Hospital, and her clinical characteristics, lab data, treatment and follow-up outcomes were reviewed. Results: A case of a 51-year-old female was presented, who underwent esophagogastroduodenoscopy (EGD) due to slight epigastric discomfort. EGD revealed multiple ulcers and erosions. Biopsies showed atypical lymphocytes infiltration with CD3(+), CD56(+), CD20(-), CD8(-), TIA(+), Granzyme B(-) and Ki-67 (75%). Epstein-Barr virus-encoded RNA in situ hybridization was negative. Four months later, repeated EGD examination showed regression of the lesions without specific treatment. Conclusion Lymphomatoid gastropathy was a unique disease entity mimicking NK/T-cell lymphomas in pathology, with the quite different profile of treatment and prognosis. It’s important to consider this issue during the differential diagnosis to avoid any excessive treatment.

Objective: To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML). Methods: Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period. Results: There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ²=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively). Conclusion DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.

Objective:To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure.Methods:Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 μg/m 3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results:After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group ( P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1β, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion:UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.

OBJECTIVE：To evaluate the price and affordability of rare disease drugs in China and provide the suggestions for the improvement of rare disease drug affordability in order to provide reference for the relevant decision-making of government departments. METHODS ：According to the List of the First Batch of Rare Diseasesand Diagnosis and Treatment Guideline for Rare Diseases（2019 edition），rare disease drugs were selected. The median price ratio （MPR）was used to evaluate the drug price level ， and the ratio of the annual drug costs to the annual disposable income of urban or rural residents was used to evaluate the affordability，and the impact of price management policieson drug prices and affordability. RESULTS and CONCLUSIONS ：A total of 71 kinds of rare disease drugs were included ，and the median MPR of them was 0.83；among them ，the median MPR of the original drugs was 1.13，and the median MPR of the generic drugs was 0.37. The annual cost of 71 rare disease drugs was 0.001-178.43 times the average annual income of urban residents ，and 0.003-456.57 times the average annual income of rural residents. There were 21 and 28 drugs whose annual cost exceeded the annual income of urban and rural residents.After the implementation of national medical insurance negotiation or volume based procurement of 14 drugs，the median MPR of these drugs decreased from 1.71 to 0.46. For urban residents ，the number of unaffordable drugs had been reduced from 8 to 0；for rural residents，it had been reduced from 10 to 5. In summary ，the price level of orphan drugs in China was slightly lower than international reference price ，but the price level of original drugs was higher than the international reference price ，and the cost of some drugs far exceeded the residents ’ability to pay. It is suggested that the government should strengthen the price management of original drugs ，promote the substitution of high-quality generic drugs for original drugs ，and improve the payment system for high-value rare disease drugs.

Antineoplastic Combined Chemotherapy Protocols ; Humans ; Multiple Myeloma ; Retrospective Studies