Objective To investigate the effects of different magnitudes of mechanical stress on human interverte-bral disc degeneration. Methods The human intervertebral disc cells were subjected to different magnitudes of mechanical stress (0, 6%, 12%, or 18%elongation) for 24 h using a Flexercell Strain Unit. The mRNA expressions of anabolic genes (col-lagen-1A1, collagen-2A1, aggrecan and versican) and catabolic genes (MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5) were examined by real-time PCR and Western blot methods. Results The expression levels of collagen-1A1 and collagen-2A1 were increased at 12%of mechanical stress, and collagen-2A1 was decreased at 18%of mechanical stress compared with those of control. The mRNA expressions of catabolic genes, MMP-13 and ADAMTS-5, were increased at 12%and 18%of mechanical stress than those of control. The mechanical stretch induced a magnitude-dependent increase in ADAMTS-4 synthesis, which was finely tuned by stretching-triggered activation of distinct mitogen-activated protein kinase cascades. Specifically, an ERK1/2 specific inhibitor, U0126, significantly inhibited the stretching-induced ADAMTS-4 expression, whereas the inhibitors of p38 and JNK, SP6000125 and SB203580, showed only slightly effect on the stretching-induced ADAMTS-4 expression. Conclusion The different magnitudes of mechanical stretch exhibited different effects on the bio-logical behavior of intervertebral disc cells, which profoundly affects the intervertebral disc degeneration.

ObjectiveTo investigate the family history of other cancers in Chinese han women with familial or sporadic breast cancer.Methodswe analyzed the clinical date of 4 847 primary breast cancer patients cancer patients were treated at the Breast Cancer,Peking University Cancer Hospital between October 2003 and February 2011,among them,465 were familial and4 382 were sporadic breast cancer patients.The differences of family history of cancers other than breast or ovarian cancers were compared between the patients with familial breast cancer and sporadic breast cancer.Results The proportion of cancers other than breast or ovarian cancers in familial breast cancer patients was significantly higher than that in sporadic breast cancer patients(29.7％ vs 20.8％,odds ratio 1.61,P＜ 0.001).Furthermore,the proportion in pancreatic cancer,prostate cancer,and renal cancer in familial breast cancer patients was significantly higher than that of sporadic breast cancer patients ( pancreatic cancer:2.2％ vs 0.8％,P =0.002 ; prostate cancer:1.5％ vs 0.3％,P ＜ 0.001 ; renal cancer:1.1％ vs 0.4％,P =0.03,respectively).And the relative risks of pancreatic cancer,prostate cancer,and renal cancer in the familial breast cancer patients were 2.90-fold,6.07-fold,and 2.97-fold higher than that of sporadic breast cancerpatients,respectively.ConclusionsOur results suggest that the relative risk of cancer other than breast or ovarian in familial breast cancer patients is significantly higher than that in sporadic breast cancer patients,especially pancreatic cancer,prostate cancer,and renal cancer.

Objective: To investigate the correlation of MDM2 SNP309 polymorphism with breast cancer risk in Chinese women. Methods: The polymorphism of MDM2 SNP309 was detected by PCR-restriction frag-ment length polymorphisms assay (PCR-RFLP) in 698 women with primary breast cancer and 525 healthy controls. Results: Compared with the T/T genotype, the G allele (T/G or G/G) was not associated with an in-creased risk of breast cancer in the entire population studied (T/G, adjusted OR=1.2, 95% CI: 0.8-1.6, P=0.30; G/G, adjusted OR=1.0, 95% CI: 0.7 ～ 1.5, P=0.88). Among postmenopausal women, the G allele (T/G or G/G) was significantly associated with an increased risk of breast cancer (T/G, adjusted OR=1.8, 95% CI:1.2～3.0, P=0.011; G/G, adjusted OR=1.9, 95% CI: 1.2～3.3, P=0.014). But this association was not ob-served among premenopausal women. Conclusion: MDM2 SNP309 heterozygous T/G genotype and homozy-gous mutant GIG genotype increase breast cancer risk in postmenopausal Chinese women.

Objective:To investigate the associations between the hormone receptors,Ki67 expression and response to neoadjuvant anthracycline-based chemotherapy in breast cancer patients.Methods:One hundred sixty-eight primary breast cancer patients received anthracycline-based neoadjuvant chemotherapy.The expression of estrogen receptor(ER),progesterone receptor(PR),and Ki67 were determined by immunohistochemistry assay in core-needle biopsy specimens prior to the chemotherapy,and pathologic response was assessed by Miller & Payne grade(G1 to G5).Results:40%(67/168)of the patients had a good pathologic response,defined as complete pathologic response(pCR or G5)and minimal residual disease(G4).Among the patients,20%(33/168)had a complete pathologic response(G5).ER or PR status was significantly associated with pathological response.Patients with PR-negative tumors had a higher pathological response rate or pCR than those with PR-positive tumors(17/67 vs 45/90,P=0.002;6/67 vs 25/90,P=0.003,respectively),whereas patients with ER-negative tumors had a higher pathological response rate than those with ER-positive tumors.Moreover,Patients with both ER-and PR-negative tumors exhibited a remarkable pathological response as compared with those with any single factor(36/17 vs 26/86,P=0.009).No association between Ki67 expression and pathological was found in this cohort of patients.There was a linear correlation between the expression of Ki-67,ER or PR status and pathologic response.Conclusion:There is a significant association between the hormone receptors and pathological response to neoadjvant anthracycline-based chemotherapy in breast cancer patients,and patients with PR-negative tumors are more likely to respond to chemotherapy.

Objective To evaluate the clinical significance of sentinel lymph nodes biopsy (SLNB) in breast cancer patients after neoadjuvant chemotherapy. Methods SLNB was performed in sixty primary breast cancer patients after neoadjuvant chemotherapy using a combination of 99mTc- Rituximab and patent blue. SLN was examined by routine pathologic examination and immunohistochemistry. Routine axillary lymph node resection was performed after SLNB. Results The successful rate of SLNB was 95% (57/60). Twenty-three cases of SLN (40% ) were metastasis positive, including 18 positive cases detected by HE staining and 5 by immunohistochemistry. SLN was the only metastasis lymph nodes in 14 out of 23 cases. One case was of false negative metastasis by SLN. The sensitivity and accuracy of SLNB were 96% (23/24) and 98% (56/57), respectively. The specificity was 100% (33/33) , the false negative rate was 4. 3% (1/23) with the negative predictive value being 97% (36/37). The positive predictive value was 100% (24/24). Internal mammary sentinel lymph node lymphoscintigraphy were positive in 11 cases but all the cases were negative in metastases by pathologic examination. Conclusion The combination of isotope imaging agent and patent blue is suitable for primary breast carcinoma after neoadjuvant chemotherapy. Internal mammary sentinel lymph node biopsy is less clinically important.

The incidence of acute kidney injury (AKI) in Neonatal Intensive Care Unit (NICU) is about 30%.The morbidity and mortality of AKI are higher in very premature infants, very low birth weight infants and infants with long mechanical ventilation.Serum creatinine (Scr) and urine output are diagnostic indicators for AKI, which usually change within 12-48 hours after the onset of irreversible injury, and cannot be used for early diagnosis and clinical intervention.Therefore, it is necessary to search for indicators of early renal insufficiency, aiming to intervene and prevent early-stage AKI or reduce the occurrence of AKI.Near-infrared spectroscopy (NIRS) is a non-invasive, continuous, real-time monitoring method, which serves as a supplement to conventional biochemical markers.It provides evidence of early-stage renal ischemia and hypoxia, which contributes to prevent or reduce AKI.This study reviews the clinical application of neonatal renal oxygen saturation monitoring, thus providing clinical reference for renal function protection in critically ill neonates to reduce the occurrence of AKI and improve their prognosis.

Objective To study the effect of adjuvant chemotherapy on the survival of patients with ER ≥ 50％,HER2 negative,lymph node negative breast cancer.Methods 428 patients from Jan 1,2004 to Dec 31,2010 were enrolled.All patients received operation plus chemoendocrine therapy (CET,n =239) or endocrine therapy (ET,n =189).Result The median follow-up time was 76.5 months,with 8.2％ loss to follow-up.The recurrence-free survival (RFS) was 93.7％ in CET group and 95.2％ in ET group,the distant disease-free survival (DDFS) was 94.6％ and 97.4％ in CET and ET group respectively.Multivariate regression indicated that the risk of tumor size ＞ 2 cm was higher than that of tumor size ≤2 cm in recurrence (HR=2.31,95％ CI 1.07-5.29,P =0.047) and metastasis (HR=4.71,95％ CI 1.47-11.85,P =0.01).Compared with CET group,however,no statistical significance was found on RFS (HR =1.08,95 ％ CI 0.46-2.57,P =0.86) and DDFS (HR =0.72,95 ％ CI 0.17-1.37,P =0.55) in ET group.Conclusions Adjuvant chemotherapy cannot improve the RFS and DDFS of ER≥50％,HER2 negative,lymph node negative breast cancer.Tumor size ＞ 2 cm was the risk factor of recurrence and distant metastasis.

Objective: To explore the application value of pedicled thoracodorsal artery perforator flap in immediate partial breast reconstruction for breast cancer. Methods: This study is a prospective case series studies. Totally 128 cases of primary breast cancer patients who prepared to receive the breast-conserving surgery combine with immediate partial breast reconstruction of pedicled thoracodorsalartery perforator flap were enrolled in Breast Cancer Prevention and Treatment Center of Peking University Cancer Hospital from June 2013 to March 2016. Finally, the operations had been completed successfully in 33 eligible cases. All patients were female with a median age of 40 years (ranging from 22 to 52 years). The perforator vessel location, the donor area design, the post-operative complications, the influence of radiation and chemotherapy had been evaluated. Results: The average diameter of thoracic dorsal artery perforators measured by Doppler ultrasound before the operation was (1.5±0.4) mm (ranging from 0.6 to 2.7 mm). The average size of flaps was 15 cm×6 cm. The average time of operations was (271±72) minutes (ranging from 120 to 245 minutes). Drainage tube removed on (4.7±2.1) days after operation (ranging from 3 to 12 days). All patients received follow-up, and there was no local recurrence and distant metastasis during a median follow-up of 17(12) months (M(Q_R)) (ranging from 5 to 38 months). All TDAP flaps were survival, the wound complication rates was 6% (2/33). Conclusions The breast reconstruction of pedicled thoracodorsal artery perforator flap is a good choice of repairing local breast defect of breast conserving surgery.Its advantages are no-influence of latissimus dorsi function and little complications in donor area.

Objective To explore the relationship of clinicopathological features and response to neoadjuvant chemotherapy in women with BRCA1 and BRCA2 mutation-negative familial breast cancer. Mte hods A total of 6 200 women with breast cancer were treated at our hospital from October 2003 to December 2012.All subjects underwent genetic testing for BRCA1 and BRCA2 genes.Patients with BRCA1 and BRCA2 mutations were excluded.This cohort of 5 842 patients with BRCA1 and BRCA2 mutation-negative breast cancer was classified as two groups: familial breast cancer patients ( n=480) and sporadic breast cancer patients ( n=5 362) .The clinicalpathological data and response to neoadjuvant chemotherapy of the 480 patients with BRCA1 and BRCA2 mutation-negative familial breast cancer and the 5 362 patients with BRCA1and BRCA 2 mutationn-egative sporadic breast cancer were compared retrospectively .Then the influencing factors of response to neoadjuvant chemotherapy were analyzed.Resu lts Among the BRCA1 and BRCA2 mutation-negative breast cancer patients, 4.4%of the patients were diagnosed before 30 years of age in the familial breast cancer group, significantly higher than that of 2.6%in the sporadic breast cancer group ( P=0.020 ) .5.0% of the patients in the familial breast cancer group had bilateral breast cancer, significantly higher than that of 2.7%in the sporadic breast cancer group ( P=0.004 ) .Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer patients, the relative risk of early-onset breast cancer (≤30 years) and bilateral breast cancer were 1.73 and 1.91, respectively, significantly higher than that in the BRCA1 and BRCA2 mutation-negative familial breast cancer cases ( P=0.020 and P=0.004) .2 964 patients in this cohort of 5 842 case sreceived neoadjuvant chemotherapy.The pathologic complete response (pCR) rate was significantly higher in the BRCA1 and BRCA2 mutation-negative familial breast cancer group than in the BRCA1 and BRCA2 mutation-negative sporadic breast cancer group (21.7%vs.14. 0%,P=0.001) .Independent factors associated with pCR in BRCA1 and BRCA2 mutation-negative breast cancer patients were tumor size less than 2 cm ( P=0.012) , histologic gradeⅢ( P<0.001) , triple-negative breast cancers (P<00.01 ), and BRCA1 and BRCA2 mutation-negative familial breast cancer(P=0.001). Conclusions Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer, BRCA1 and BRCA2 mutation-negative familial breast cancer is more likely diagnosed before the age of 30 years and has a higher risk to develop bilateral breast cancer.BRCA1 and BRCA2 mutation-negative familial breast cancers are more likely to respond to neoadjuvant chemotherapy than BRCA1 and BRCA2 mutation-negative sporadic breast cancer.

Objective To explore the relationship of clinicopathological features and response to neoadjuvant chemotherapy in women with BRCA1 and BRCA2 mutation-negative familial breast cancer. Mte hods A total of 6 200 women with breast cancer were treated at our hospital from October 2003 to December 2012.All subjects underwent genetic testing for BRCA1 and BRCA2 genes.Patients with BRCA1 and BRCA2 mutations were excluded.This cohort of 5 842 patients with BRCA1 and BRCA2 mutation-negative breast cancer was classified as two groups: familial breast cancer patients ( n=480) and sporadic breast cancer patients ( n=5 362) .The clinicalpathological data and response to neoadjuvant chemotherapy of the 480 patients with BRCA1 and BRCA2 mutation-negative familial breast cancer and the 5 362 patients with BRCA1and BRCA 2 mutationn-egative sporadic breast cancer were compared retrospectively .Then the influencing factors of response to neoadjuvant chemotherapy were analyzed.Resu lts Among the BRCA1 and BRCA2 mutation-negative breast cancer patients, 4.4%of the patients were diagnosed before 30 years of age in the familial breast cancer group, significantly higher than that of 2.6%in the sporadic breast cancer group ( P=0.020 ) .5.0% of the patients in the familial breast cancer group had bilateral breast cancer, significantly higher than that of 2.7%in the sporadic breast cancer group ( P=0.004 ) .Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer patients, the relative risk of early-onset breast cancer (≤30 years) and bilateral breast cancer were 1.73 and 1.91, respectively, significantly higher than that in the BRCA1 and BRCA2 mutation-negative familial breast cancer cases ( P=0.020 and P=0.004) .2 964 patients in this cohort of 5 842 case sreceived neoadjuvant chemotherapy.The pathologic complete response (pCR) rate was significantly higher in the BRCA1 and BRCA2 mutation-negative familial breast cancer group than in the BRCA1 and BRCA2 mutation-negative sporadic breast cancer group (21.7%vs.14. 0%,P=0.001) .Independent factors associated with pCR in BRCA1 and BRCA2 mutation-negative breast cancer patients were tumor size less than 2 cm ( P=0.012) , histologic gradeⅢ( P<0.001) , triple-negative breast cancers (P<00.01 ), and BRCA1 and BRCA2 mutation-negative familial breast cancer(P=0.001). Conclusions Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer, BRCA1 and BRCA2 mutation-negative familial breast cancer is more likely diagnosed before the age of 30 years and has a higher risk to develop bilateral breast cancer.BRCA1 and BRCA2 mutation-negative familial breast cancers are more likely to respond to neoadjuvant chemotherapy than BRCA1 and BRCA2 mutation-negative sporadic breast cancer.