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Background Microwave ablation (MWA) and radiofrequency ablation (RFA) have recently attracted interest as minimally invasive treatment modalities for papillary thyroid carcinoma (PTC). However, the ablation outcomes of T1N0M0 PTC are not well characterized. Purpose To evaluate the efficacy and safety of thermal ablation (MWA or RFA) of solitary T1N0M0 PTC in patients who were ineligible for (due to presence of comorbid cardiovascular disease, renal failure, other malignancy, etc) or who refused surgery. Materials and Methods This was a retrospective multicenter study of 847 patients (660 women) who underwent thermal ablation for PTC (673 T1a, 174 T1b) between March 2015 and March 2020; of these patients, 645 underwent MWA and 202 underwent RFA. The mean age of patients was 46 years ± 11 (standard deviation) (age range, 18-81 years); the mean follow-up time was 22 months ± 13 (range, 6-60 months). Changes in tumor size and volume and the rates of technical success, tumor disappearance, disease progression, and complications were assessed. Results The technical success rate was 100%. Relative to preablation measurements, the maximum diameter and volume of the ablation zone increased during the 1st month after ablation (P < .001), whereas there was no difference by the 3rd month; subsequently, the tumors showed reduction in size at 6, 9, and 12 months (all P < .001). Complete disappearance of tumors occurred in 68% of patients (577 of 847; 69% [466 of 673] in the T1a group vs 64% [111 of 174] in the T1b group; P < .001). The postablation disease progression rate was 1.1% (nine of 847 patients; 0.9% [six of 673 patients] in the T1a group vs 1.7% [three of 174 patients] in the T1b group; P = .54). The overall complication rate was 3.4% (29 of 847 patients; 2.7% [18 of 673 patients] in the T1a group vs 6.3% [11 of 174 patients] in the T1b group; P = .02). Conclusion This multicenter study provided evidence that thermal ablation is an effective and safe treatment option in selected -patients with solitary T1N0M0 papillary thyroid carcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Baek and Cho in this issue.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer., Chinese breast cancer patients have not been well represented in clinical sequencing studies. Here the authors analyse the mutational landscape of 1,134 Chinese breast cancer patients, finding actionable targets and a higher prevalence of p53 and Hippo pathway mutations compared to Western cohorts.

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day −21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) , high density lipoprotein cholesterol (HDL C) , very low density lipoprotein (VLDL), glucose, insulin, β-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDL C, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows.

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, and molecular subtyping may result in improved diagnostic precision and targeted therapies. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we conducted the FUTURE trial (ClinicalTrials.gov identifier: NCT03805399), a phase Ib/II subtyping-based and genomic biomarker-guided umbrella trial, to evaluate the efficacy of these targets. Patients with refractory metastatic TNBC were enrolled and stratified by TNBC subtypes and genomic biomarkers, and assigned to one of these seven arms: (A) pyrotinib with capecitabine, (B) androgen receptor inhibitor with CDK4/6 inhibitor, (C) anti PD-1 with nab-paclitaxel, (D) PARP inhibitor included, (E) and (F) anti-VEGFR included, or (G) mTOR inhibitor with nab-paclitaxel. The primary end point was the objective response rate (ORR). We enrolled 69 refractory metastatic TNBC patients with a median of three previous lines of therapy (range, 1–8). Objective response was achieved in 20 (29.0%, 95% confidence interval (CI): 18.7%–41.2%) of the 69 intention-to-treat (ITT) patients. Our results showed that immunotherapy (arm C), in particular, achieved the highest ORR (52.6%, 95% CI: 28.9%–75.6%) in the ITT population. Arm E demonstrated favorable ORR (26.1%, 95% CI: 10.2%–48.4% in the ITT population) but with more high grade (≥ 3) adverse events. Somatic mutations of TOP2A and CD8 immunohistochemical score may have the potential to predict immunotherapy response in the immunomodulatory subtype of TNBC. In conclusion, the phase Ib/II FUTURE trial suggested a new concept for TNBC treatment, demonstrating the clinical benefit of subtyping-based targeted therapy for refractory metastatic TNBC.

To investigate the accuracy and safety of pedicle screw placement assisted by orthopedic robot and C-arm fluoroscopy.The clinical data of 36 patients with spinal diseases underwent surgical treatment from January 2019 to August 2020 was retrospectively analyzed. Among them, 18 cases were implanted pedicle screws assisted by orthopaedic robot(observation group), including 12 males and 6 females, aged from 16 to 61 years with an average of (38.44±3.60) years;there were 1 case of adolescent scoliosis, 1 case of spinal tuberculosis, 7 cases of lumbar spondylolisthesis, 4 cases of thoracic fracture and 5 cases of lumbar fracture. Another 18 cases were implanted pedicle screws assisted by C-arm fluoroscopy(control group), including 10 males and 8 females, aged from 18 to 58 years with an average of (43.22±2.53) years;there were 1 case of adolescent scoliosis, 6 cases of lumbar spondylolisthesis, 6 cases of thoracic fracture and 5 cases of lumbar fracture. The intraoperative fluoroscopy times, nail placement time and postoperative complications were recorded in two groups. CT scan was performed after operation. The Gertzbein-Robbins standard was used to evaluate the accuracy of pedicle screw placement which was calculated.The number of intraoperative fluoroscopy in observation group was(6.89±0.20) times, which was significantly higher than that in control group(14.00±0.18)times(Orthopaedic robot assisted pedicle screw placement has the advantages of less fluoroscopy times, shorter screw placement time and higher accuracy, which can further improve the surgical safety and has a broad application prospect in the orthopaedic.

To explore the clinical application of Orthopedic Tianji Robot in the treatment of thoracolumbar fractures with minimally invasive percutaneous pedicle screw internal fixation.The clinical data of 46 patients with thoracolumbar fractures treated by minimally invasive percutaneous pedicle screw internal fixation from June 2018 to January 2020 in Gansu Provincial People's Hospital was retrospectively analyzed. According to the different aided equipments, the patients were divided into a C-arm X-ray plus robot assisted nail placement group (observation group) and simple C-arm X-ray assisted nail placement group (control group). Twenty-two patients in observation group, including 12males and 10 females, aged from 24 to 61 years old, with a mean of(40.23±12.19) years, 3 cases were TAll patients were followed up for 5 to 12 months with an average of (7.07±0.83) months. There was no significant differences in intraoperative blood loss, operation time and hospitalization days between two groups (P0.05). The number of intraoperative fluoroscopy was (5.62±0.51) times in observation group and (12.54±0.52) in control group, the difference between two groups was statistically significant (P0.05). The VAS, the percentage of the height of the injured vertebra anterior edge and the Cobb angle of the injured vertebral plane at each time point after operation were improved(P0.05), but the difference between two groups was not statistically significant (P0.05). One case of postoperative incision infection occurred in the control group, which was cured after active dressing changes. There were no serious complications such as screw loosening and breakage in all patients, and there was no statistically significant difference in the incidence of complications between two groups(P0.05). The postoperative nail placement accuracy ratesof the observation group and the control group were 98.4% (126/128) and 90.3% (121/134), respectively, and the difference was statistically significant (P0.05).In the surgical treatment of thoracolumbar fractures, compared with simple C-arm fluoroscopy, the pedicle screw placement assisted by Orthopedic Tianji Robot overcomes the shortcomings of surgeon's physiological tremor, fatigue and multiple intraoperative fluoroscopy, improves the accuracy of screw placement, and is a more accurate and safer way of pedicle screw placement for thoracolumbar fractures.

Background Endocrine therapy is the preferred treatment for patients with hormone receptor ‐positive metastatic breast cancer (MBC). While visceral metastasis is a negative prognostic factor, few studies have distinguished between the prognoses of patients with metastases at different visceral sites. Patients and methods In total, 398 patients receiving fulvestrant 500 mg at a single center over a 6‐year period were analyzed. Logistic regression models were used to identify the prognostic factors associated with progression‐free survival (PFS). Kaplan‐Meier analysis was used to compare the PFS of patients with lung and liver metastases. Results Baseline visceral metastases were present in 233 patients, including 138 with lungw/o liver metastases (lung metastases without liver involvement), 51 with liverw/o lung metastases (liver metastases without lung involvement) and 41 with lung and liver metastases. The median PFS was 6.8 months (5.6 and 9.2 months for visceral and nonvisceral metastases, respectively, P = .028). PFS was longer in patients with lungw/o liver metastases than in those with liverw/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P, Our results demonstrated that patients with liver metastases respond poorly to fulvestrant, while in contrast, the efficacy of fulvestrant treatment in patients with lung metastases but no liver involvement was comparative to that of patients with non‐visceral metastases. Therefore, we suggest that categorizing MBC into “liver” and “non‐liver” metastases may better reflect patient prognosis compared to “visceral” and “non‐visceral” metastasis.

High on-treatment platelet reactivity (HTPR) after clopidogrel administration in patients with acute coronary syndrome (ACS) has been associated with an increased risk of adverse events. Our previous studies reported that half-dose ticagrelor provides a similar inhibitory effect on adenosine diphosphate (ADP)–induced platelet aggregation as standard-dose ticagrelor, but half-dose of ticagrelor has not been studied in Chinese ACS patients with HTPR. This study aimed to compare the antiplatelet action of half-dose ticagrelor with high-dose clopidogrel in ACS patients with HTPR. In this single-center randomized controlled trial, 80 (of 418 screened, 19.13%) ACS patients with HTPR while on clopidogrel were randomized to either half-dose ticagrelor (90 mg LD, then 45 mg twice daily) or high-dose clopidogrel (150 mg once daily). Platelet function was assessed by thromboelastography (TEG) and light transmission aggregometry (LTA), and adverse events were monitored throughout the study for 30 days. The ADP-induced platelet inhibition rate (IR) as measured by TEG was significantly higher for half-dose ticagrelor compared with high-dose clopidogrel (70.40% [61.10%–91.70%] vs. 44.25% [34.67%–79.07%], p = 0.001). The repeated HTPR rate was dramatically higher for high-dose clopidogrel compared with half-dose ticagrelor (6 of 32, 18.75% vs. 1 of 35, 2.85%; p = 0.04). No patients in either treatment group exhibited a major bleeding event or other adverse events. In ACS patients with HTPR, half-dose ticagrelor is more effective than high-dose clopidogrel in reducing platelet reactivity (NCT03062462).

To investigate the clinical efficacy and advantage of minimally invasive transforaminal lumbar interbody fusion under microscope-assisted Zista channel in the treatment of degreeⅠandⅡdegenerative lumbar spondylolisthesis.The clinical data of 18 patients with degenerative lumbar spondylolisthesis treated by microscope-assisted Zista channel MIS-TLIF operation from January 2017 to March 2018 were analyzed retrospectively. There were 10 males and 8 females with an average age of 59 years (48 to 70). The course of spondylolisthesis ranged from 6 months to 5 years with an average of 33 months. The segment of spondylolisthesis was LAll the patients completed the operation successfully and were followed up more than 12 months after operation. Operation time was(160.45±34.98) min, intraoperative blood loss was (88.32±21.12) ml, postoperative drainage volume was (50.34 ±18.22)ml, and walking time after operation was (20.65±6.25) h. Preoperative and postoperative at 7 days, 3 months, 12 months, VAS score of low back pain was 7.81±2.16, 4.19±1.17, 2.25±0.62 and 1.53±0.58 respectively, VAS score of leg pain was 8.47± 2.21, 3.45±0.86, 2.31±0.73 and 1.43±0.47, JOA score was 12.01±2.33, 18.56±3.12, 23.54±3.31 and 26.34±2.65. There were significant differences in VAS and JOA scores between preoperative and postoperative (MIS-TLIF under microscope-assisted Zista channel has obvious minimally invasive advantages in the treatment of degreeⅠandⅡdegenerative lumbar spondylolisthesis, and it is a safe and effective method.

circRNAs play important roles in regulating gene expression at both transcriptional and post transcriptional levels and involve in a variety of human diseases. But up to now, it is still unclear whether circRNAs are involved in the occurrence and development of sepsis induced acute respiratory distress syndrome (ARDS). In the present research, we collected lung tissues of sepsis induced ARDS patients (n = 3) and brain dead patients without ARDS (n = 3). From the results of genome-wide sequencing, a total of 272 significantly up-regulated and 231 significantly down-regulated circRNAs were obtained. Combining the previous sequencing results in the plasma of ARDS patients, 11 up-regulated and 3 down-regulated circRNAs simultaneously in plasma and lung tissues were identified. Pathway enrichment analysis showed that the co differentially expressed circRNAs might be involved in the regulation of ECM-receptor interaction and adherens junction etc. In conclusion, these data indicates that circRNAs may involve in the progression of sepsis induced ARDS.

Background Could nutritional status serve as prognostic factors for coronavirus disease 2019 (COVID-19)? The present study evaluated the clinical and nutritional characteristics of COVID-19 patients and explored the relationship between risk for malnutrition at admission and in-hospital mortality. Methods A retrospective, observational study was conducted in two hospitals in Hubei, China. Confirmed cases of COVID-19 were typed as mild/moderate, severe, or critically ill. Clinical data and in-hospital death were collected. The risk for malnutrition was assessed using the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the Controlling Nutritional Status (CONUT) via objective parameters at admission. Results Two hundred ninety-five patients were enrolled, including 66 severe patients and 41 critically ill patients. Twenty-five deaths were observed, making 8.47% in the whole population and 37.88% in the critically ill subgroup. Patients had significant differences in nutrition-related parameters and inflammatory biomarkers among three types of disease severity. Patients with lower GNRI and PNI, as well as higher CONUT scores, had a higher risk of in-hospital mortality. The receiver operating characteristic curves demonstrated the good prognostic implication of GNRI and CONUT score. The multivariate logistic regression showed that baseline nutritional status, assessed by GNRI, PNI, or CONUT score, was a prognostic indicator for in-hospital mortality. Conclusions Despite variant screening tools, poor nutritional status was associated with in-hospital death in patients infected with COVID-19. This study highlighted the importance of nutritional screening at admission and the new insight of nutritional monitoring or therapy.

Background: Bloodstream infection (BSI) are prone to circulation disorders, which portend poor outcome. The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for circulation disorders, but the prognostic value of Pcv-aCO2 in BSI patients remains unclear. This study was to investigate the association of Pcv-aCO2 with adverse events in BSI patients. Methods: The patients with BSI between August 2014 and August 2017 were prospectively enrolled. Clinical characteristic and laboratory results were collected. We analyzed the association of the level of Pcv-aCO2 with clinical variables and 28-day mortality. Results: A total of 152 patients were enrolled. The Pcv-aCO2 was positively correlated with white blood cell count (r=0.241, p=0.003), procalcitonin (r=0.471, p6mmHg had a worse prognosis than those without (log rank=32.10, p6 mmHg had 81.1% sensitivity and 78.8% specificity for predicting 28-day mortality. Conclusion: Pcv-aCO2 may be a simple and valuable biomarker to assessment of 28-day mortality in patients with BSI.

To investigate the clinical efficacy and advantages of the full endoscopic I See technique for the single-segment degenerative lumbar spinal stenosis.The clinical data of 38 patients with the single-segment degenerative lumbar spinal stenosis treated by full endoscopic I See technique from January 2017 to March 2018 were analyzed retrospectively. There were 16 males and 22 females, aged from 35 to 79 years with an average of(53.45±12.56) years. Five cases were LAll the patients were followed up for more than 12 months after operation. The length of operation was from 55 to130 (86.0± 17.5) min. Intraoperative blood loss was ranging from 10 to 50 (17±6) ml, and the hospitalization length was from 3 to 7 days with an average of 4.6 days. The VAS scores of low back pain assessed before operation, and 3 d, 3 months, 12 months post operation were 6.67 ±1.25, 3.87 ±1.35, 2.55 ±1.21, 2.05 ±0.97, respectively, and the differences were statistically significant (P0.05);VAS scores of leg pain at these time points were 7.85±2.62, 3.31±1.42, 2.02±1.13, 1.85±0.86, respectively, and the differences were statistically significant (Full endoscopic I See technique is effective in the treatment of single-segment degenerative lumbar spinal stenosis, with the advantages of less trauma, shorter hospital stay, and faster recovery.

Ameloblastoma is the most common odontogenic tumor of epithelial origin. These tumors are benign in nature but have a high rate of recurrence and possible malignant development when treated inadequately. However, recurrent ameloblastomas in bone grafts are rare. This article presents a rare case of a multiple recurrent ameloblastoma, with the last recurrence in a nonvascularized free iliac bone graft of the mandible, reconstructed with vascularized deep circumflex iliac artery free flap for the surgical defect. Furthermore, an updated review of the literature on recurrent ameloblastomas affecting the bone graft is provided.

To investigate the clinical effects of the Halo-pelvic traction combined with posterior instrumentation correction and internal fixation for the treatment of severe and rigid scoliosis.From January 2015 to 2019 May, 16 patients with severe and rigid scoliosis were treated by the Halo-pelvic traction combined with posterior instrumentation correction. There were 7 males and 9 females, aged 14 to 28 years with an average of 17.6 years, Cobb angle was 90° to 140° with an average of (108.84±17.93) °. Including congenital scoliosis in 10 cases (6 cases of dyssegmented scoliosis, 3 cases of dysplasia, 1 case of mixed scoliosis), idiopathic scoliosis in 4 cases and neurofibromatosis in 2 cases. All patients in group had scoliosis corrected by Halo-pelvic distraction combined with posterior instrumentation correction and internal fixation. Among them, 7 cases were treated with self-made guide device for iliac bone puncture, and the other cases with traditional bare hands. The height, scoliosis Cobb angle, kyphosis Cobb angle and correction rate of 16 patients before and after surgery were observed.The body height was corrected from (144.88±6.32) cm to (154.56±7.87) cm ; Cobb angle of scoliosis was corrected from (108.84±17.93) ° to (42.12±7.29) °, Cobb angle of kyphosis was corrected from (64.18±16.39) ° to (33.81±6.06) °. After the Halo pelvic traction, the body height increase, Cobb angle of scoliosis and kyphosis were changed with the mean of (7.06± 5.65) cm, (41.50±9.09)%, (30.52±9.66)%, respectively. After the stage Ⅱ surgical correction, the body height increase, Cobb angle of scoliosis and kyphosis were changed with the mean of (2.63±1.78) cm, (32.47±10.80)%, (15.55±9.47)% (The baseline Cobb angle referenced by the correction rate was the Cobb angle of the previous treatment). The body height increase and correction rate of Cobb angle of scoliosis and kyphosis with staged traction combined with surgery was (9.69±5.42) cm, (61.09 ± 5.03)%, (46.07±8.60)%. There was significant difference in body height increase, correction rate of Cobb angle of scoliosis and kyphosis between before and after each period of treatment (Treatment of severe and rigid scoliosis with Halo-pelvic traction combined with stage Ⅱ surgical correction can significantly correct deformities and improve appearance, and has fewer surgical complications and strong clinical operability.

Background CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46–9.00] months for GP arm and 6.07 (95% CI 5.32–6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration ClinicalTrials.gov, NCT01287624.

Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; p non-inferiority superiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [ vs one [ vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1–4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.

We sought to investigate the impact of hormone receptor (HR) status and distant recurrence-free interval (DRFI) on the degree of overall survival (OS) benefit from palliative trastuzumab-containing treatment in HER2-positive metastatic breast cancer (MBC). Here, we retrospectively identified 588 eligible HER2-positive patients with postoperative distant recurrence. DRFI of HR+HER2+ MBC patients (median: 30.7 months, IQR: 18.5–45.9, P 24 months is an independent favourable prognostic factor for both HR−HER2+ patients (Hazard Ratio (HzR) = 0.55, 95% CI: 0.39–0.76, P P < 0.001). Upon further analysis of the interaction between trastuzumab and DRFI, the degree of trastuzumab benefits in HR−HER2+ MBC patients remained basically unchanged regardless of DRFI length. Unlikely, the degree in HR+HER2+ MBC patients decreased gradually along with DRFI extending, indicating that trastuzumab failed to translate into an OS benefit for late recurrent (DRFI > 5years) HR+HER2+ MBC patients.

The objective of this study was to investigate correlations between oxidative stress, metabolism of mineral elements, and lameness in dairy cows. Forty multiparous Chinese Holstein dairy cows were selected and divided into two groups (healthy vs lame, n = 20) by gait score. The experiment lasted for 60 days and samples of hair, blood, and hoof were collected at days 0, 30, and 60 of experiment period, individually. Compared with healthy cows, elevation of MDA, CTX-II, COMP levels, and GSSG/GSH ratio together with depletion of SOD and MT levels in the serum were revealed in lame cows. Simultaneously, significant decreased contents of Zn, Cu, and Mn in the serum, hair, and hoof samples were shown in lame cows, but there was no obvious difference in contents of P, Mg, and Ca (except hoof Ca) in the serum, hair, and hoof between healthy and lame cows. In addition, histological examination and the hardness test demonstrated a poor hoof quality in lame cows. In summary, oxidative stress is implicated in the pathogenesis of lameness caused by imbalance of nutrients (especially selective minerals promoting healthy hoof growth) in dairy cows.

Background The aim of this study was to assess curative effect of hysteroscopic and laparoscopic myomectomy for type II submucous myomas between 3 and 5 cm in diameter and explore the optimal surgical indications. Methods A retrospective analysis was performed of those who underwent hysteroscopic or laparoscopic myomectomy from January 2008 to January 2013. The patients were divided into three subgroups according to the myomas diameter (namely, 30 mm ≤ myomas diameter

In this article, inconsistency of the association of polymorphisms of fibroblast growth factor receptor 2 (FGFR2) with breast cancer is noted. Three commonly studied FGFR2 polymorphisms including rs1219648 (AG), rs2420946 (CT), and rs2981582 (CT) were selected to explore their association with risk of development of breast cancer by meta-analysis of published case-control studies. The results showed that all these three polymorphisms were significantly associated with altered breast cancer risk in any model (co-dominant, dominant, or recessive model) and in stratification based on ethnicity and study design. In the subgroup analyses for postmenopausal women, significantly increased risks were found for rs1219648 and rs2420946 in any model. This meta-analysis suggests that FGFR2 is likely an important genetic marker contributing to susceptibility of breast cancer. We recommend that these single nucleotide polymorphisms to be included in future association studies and functional assays.

The human chemokine receptor CCRL2 is a member of the atypical chemokine receptor family. CCRL2 is unable to couple with G-proteins and fails to induce classical chemokine signaling for the highly conserved DRYLAIV motif essential for signaling has been changed to QRYLVFL. We investigated whether CCRL2 is involved in the chemotaxis, invasion, and proliferation of human breast cancer cells. Firstly, expression of CCRL2 was determined in six breast cancer cell lines by real-time RT-PCR and Western blot. Then, we established stable cell lines overexpressing CCRL2 to explore the function of CCRL2 in chemotaxis and invasion by transwell assays, and the signaling downstream was further investigated. The effect of CCRL2 on proliferation was detected by colony formation assays and tumor xenograft study. We found that stable overexpression of CCRL2 in MDA-MB-231 and BT-549 cells attenuated the chemotaxis and invasion stimulated by its ligand CCL2. CCRL2 inhibits p38 MAPK (p38) phosphorylation and up-regulates the expression of E-cadherin. This effect was eliminated by the inhibitor of p38 MAPK. CCRL2 inhibited the growth of breast cancer cells in vitro and in vivo. Our results suggest that CCRL2 functions as a tumor suppressor in human breast cancer cells.

Purpose Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa–mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC. Methods Eligibility criteria included human epidermal growth factor receptor 2–negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m2 orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival. Results A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0–4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7–9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5–3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting. Conclusion Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA–related adverse events. Trial Registration ClinicalTrials.gov NCT01380808

To evaluate the effects of chelated Zn/Cu/Mn on redox status, immune responses and hoof health in lactating Holstein cows, 48 head in early lactation were divided into healthy or lame groups according to their gait score. Cows were fed the same amount of Zn/Cu/Mn as sulfate salts or in chelated forms for 180 days, and foot-and-mouth disease (FMD) vaccine was injected at day 90. The results showed that lame cows had lower antioxidant function, serum Zn/Mn levels, hair Cu levels, and hoof hardness. Moreover, increased antioxidant status, FMD antibody titers, serum and hair levels of Zn/Cu/Mn, and hoof hardness and decreased milk fat percent and arthritis biomarkers were observed in cows fed chelated Zn/Cu/Mn. In summary, supplementation with chelated Zn/Cu/Mn improved antioxidant status and immune responses, reduced arthritis biomarkers, and increased accumulation of Zn/Cu/Mn in the body and hoof hardness in dairy cows.

AIM: The objectives of this study were to determine if the baseline SUVmax measured by F-FDG PET/CT correlates with molecular subtype and to explore the impact of baseline SUVmax on the survival of patients with metastatic breast cancer (MBC). METHODS: Patients with MBC were screened with PET/CT from February 2007 until December 2010. Multivariate linear regression analysis was performed to identify independent variable correlation with SUVmax. Prognostic variables identified by univariate analysis, with P < 0.1, were analyzed in the multivariate Cox model. RESULTS: A total of 244 MBC patients were eligible for this study. Multivariate linear regression analysis showed that molecular subtype, visceral metastasis, and number of metastatic organs could be used to predict the logarithmic values of SUVmax (lgSUVmax) for previous untreated MBC patients, whereas for those with 1 or more line previous treatment, the number of metastatic organs was identified as the only independent variable correlating with lgSUVmax. Cox regression analysis indicated that only in patients with previously untreated MBC did baseline SUVmax (continuous variable) act as an independent prognostic factor (hazard ratio = 1.049 for progression-free survival, 1.124 for overall survival). CONCLUSIONS: Baseline SUVmax correlates with molecular subtypes only in previously untreated MBC patients. PET/CT imaging can be used as a potential prognostic tool for patients with newly diagnosed MBC.

Cardiac arrest is one of the most serious complications of acute myocardial infarction (AMI), especially in the out-of-hospital patients. There is no general consensus as to whether percutaneous coronary intervention (PCI) is effective in treating ST-segment elevation myocardial infarction (STEMI) patients complicated by out-of-hospital cardiac arrest (OHCA). In our study, we evaluated the efficacy of PCI in treating STEMI patients complicated by OHCA through observing their clinical conditions in hospital; including total mortality, adverse cardiac events, stroke, acute renal failure, and gastrointestinal bleeding events.A total of 1827 STEMI patients were enrolled in this study, where 81 were STEMI with OHCA. Between the patients with and without OHCA, and the OHCA patients with and without PCI, we compared the clinical characteristics during hospitalization, including total mortality and incidences of adverse cardiac events, and stroke.Compared to the patients without OHCA, the OHCA patients had significantly lower systolic blood pressure (P0.05) and a faster heart rate (P0.05), and a higher percentage of Killip class IV or Glasgow coma scale (GCS) ≤ 7 on admission (P0.001). And the in-hospital mortality was higher in the OHCA patients (55.6% vs. 2.4%, P0.001). Comparing the OHCA patients without PCI to the patients with PCI, there was no obvious difference of heart rate, blood pressure or the percentage of Killip class IV and GCS ≤ 7 on admission, but the incidences of cardiogenic shock, stroke were significantly lower in the with-PCI group during hospitalization (P0.001, P0.05). And the in-hospital mortality of the OHCA patients receiving PCI was significantly lower (36.7% vs. 84.3%, P0.001).During hospitalization, the incidence of adverse events and mortality are higher in the STEMI with OHCA patients, comparing with the STEMI without OHCA. Emergency PCI reduces the incidence of adverse events and decreases mortality during hospitalization, which is effective for treating STEMI with OHCA patients.

The aim of this study was to evaluate the efficacy and tolerability of combination chemotherapy with epirubicin, cisplatin, 5-fluorouracil (ECF regimen), and Chloroxoquinoline in patients with metastatic gastric cancer.Twenty-two patients with histologically confirmed metastatic gastric adenocarcinoma were treated with a combination of epirubicin 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 1), 5-fluorouracil 500 mg/m2 (days 1 to 5), and Chloroxoquinoline 400 mg (days 1 to 21), with the cycle repeated every three weeks.Twenty patients were evaluable for response. One case of (5%) complete response, seven of (35%) partial response, nine (45%) of stable disease, and three (15%) of progressive disease were observed, giving an overall treatment response rate of 40%. Median survival time was 9.4 months, median progression-free survival was 6.1 months, and the 1-year survival rate was 25%. Both hematologic and non-hemotologic toxicities were well tolerated and no treatment-related deaths occurred. In patients who received Chloroxoquinoline maintenance monotherapy after six cycles of the combination regimen, progression-free survival was nine months.The combination regimen demonstrated comparable efficacy and acceptable safety profiles in patients with metastatic gastric cancer. Chloroxoquinoline maintenance monotherapy has a tendency to increase progression-free survival.

To analyze the injuries after the earthquake with otorhinolaryngology symptoms and the characteristics of with injuries and to provide some information when dealing with similar disasters in the future.The basic information of earthquake-related injuries with otorhinolaryngology symptoms was collected in 11 large and medium-sized hospitals (including foreign medical teams) in Mianyang City and the surrounding four hard-hit counties. Their characteristics were analyzed together.There were 289 patients that have otorhinolaryngology symptoms in the 11 included hospitals, among them there were 217 cases have definite records that could be analyzed. The data showed that damage to ear and head and neck injuries as the main symptoms was large proportion of injuries suffer multiple fractures and soft tissue injuries such as skin abrasions . Nose injury and facial fractures were also common. Orbital fracture and eye damage could be combined occurred. Brain injury and skull fractures often occurred while trachea and throat injury was rare happened.Different disaster cause different damage. After the establishment of disaster-related injuries in professional spectrum more active and effective could be behaved in life rescue and the arrangement of personnel and material when dealing with similar situations.

To study the microbiology, clinical features and treatment outcomes of hospital-acquired pneumonia (HAP) caused by Acinetobacter baumannii.Six cases of HAP, caused by Acinetobacter baumannii producing PER-1 type extended-spectrum beta-lactamase verified by molecular biological methods, were studied in Bethune International Peace Hospital, from January to August 2005. Clinical data were collected and analyzed. Pulsed-field gel electrophoresis (PFGE) were used to analyze the homology of these strains. The genes of beta-lactamase (BLA), aminoglycoside-modifying enzymes (AME), resistant to disinfectant-sulfanilamide (qacEDelta1-sul1), and class 1 integrase (intl1) were analyzed using PCR and verified by DNA sequencing.Among these 6 strains of Acinetobacter baumannii, five were susceptible only to imipenem, and 4 were susceptible to meropenem. The PFGE types identified from these isolates were A1 (n=2) and A2-A5 (n=1, respectively). They all were positive for PER-1, TEM-1, and genes of qacEDelta1-sull and intl1. Three of them harbored genes of aac (3)-I and aac (6')-I. Two had aac (3)-I and ant (3'')-I. One had aac (3)-I. All the patients had severe underlying diseases, and had received mechanical ventilation. They all had received broad spectrum antibiotics within 15 days before Acinetobacter baumannii were identified. Although carbapenem and/or cefoperazone/sulbactam had been used, only 3 patients survived.The 6 PER-1 type extended-spectrum beta-lactamase-producing Acinetobacter baumannii isolates were closely related and had complex mechanisms of drug resistance. The prognosis of patients infected by them was poor.

DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.

It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro--Arg and p73 exon 2 G4C14--A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided.The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.

DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. This study was to examine the correlations of polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer (NSCLC) to platinum-based chemotherapy.Treatment outcomes of 200 advanced NSCLC patients, treated with platinum-based chemotherapy, were evaluated. XPC-PAT, XPD Lys751Gln (rs1052559), and ERCC1 C8092A (rs1052559) were genotyped by polymerase chain reaction-amplified fragment length polymorphism (PCR-AFLP) or PCR-restrictive fragment length polymorphism (PCR-RFLP) methods in the 200 patients. Unconditional logistic regression model was used to analyze the correlation of genetic polymorphisms to clinical response.The distributions of XPC-PAT genotypes differed significantly between response group (complete response + partial response) and un-response group (stable disease + progressive disease)(P=0.023). The XPC LL genotype carriers had higher response rate than the SS genotype carriers (OR=3.04; 95% CI=1.25-7.41, P= 0.015). The XPD Lys751Gln and ERCC1 C8092A polymorphisms were not found to be associated with platinum-based chemotherapy. However, these 3 genetic polymorphisms in nucleotide excision repair system had interaction in the drug sensitivity (P=0.021).The genetic polymorphisms of XPC-PAT, XPD Lys751Gln, and ERCC1 C8092A in nucleotide excision repair system may be associated with sensitivity of NSCLC patients to platinum-based chemotherapy.

To observe the histological changes in the fibrotic and inflammatory tissues in response to interferon alpha treatment in patients with chronic viral hepatitis B.Sixteen patients with chronic viral hepatitis B in S3-S4 stages established by pathological examination were treated with interferon alpha for 6-9 months, and the degree of liver fibrosis and inflammation were examined 3 times during the treatment. The expression of Fas, transforming growth factor beta1 (TGFbeta1) and HBcAg in the liver tissues were detected by immunohistochemistry, and DNA fragmentation was examined by TUNEL assay. The levels of the serum markers for liver fibrosis and liver function were also measured.Patients with liver fibrosis in S3-S4 stages had high pathological expression of Fas and TGFbeta1 with severe DNA damage in the liver tissues. After 3 months of interferon therapy, the expression of Fas and TGFbeta1 were lowered (P0.05), and further treatment till 3-9 months resulted in gradual decrease in the degree of hepatic fibrosis and cell apoptosis (P0.05), with improved serum liver fibrosis indices and liver function.Interferon alpha may alleviate liver fibrosis and suppress cell apoptosis in patients in S3-S4 stages after a 6- to 9-month continuous treatment.

Nucleotide excision repair has been shown to have great impact on the sensitivity of tumors to platinum-based chemotherapy. This study was to examine the association between genetic polymorphisms in XPC and XPD, two important components in nucleotide excision repair system, and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer.Patients (n = 151) treated with platinum-based chemotherapy were genotyped for the AT dinucleotide insertion or deletion in intron 9 of XPC or Lys751Gln polymorphism in XPD. Clinical response to chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model and adjusted for sex, age, clinical stage, and regime of chemotherapy.The overall response rate to the chemotherapy (CR + PR) was 35.1%, with 1 CR, 52 PR, 75 SD, and 23 PD. It was found that patients with the XPC LL genotype had significantly higher response rate than patients with the XPC SS genotype (adjusted OR = 3.19, 95% CI = 1.11 - 9.17; P = 0.031). However, no association was found between the XPD Lys751Gln polymorphism and response to the chemotherapy. In addition, these two polymorphisms seemed to have synergic effect, with the OR being 2.90 (95% CI = 1.07 - 7.86) for patients carrying the XPC LL and XPD Lys/Lys genotypes compared with those carrying the XPC SS or SL and XPD Lys/Lys genotypes.These results suggest that genetic polymorphisms in nucleotide excision repair might be associated with clinical response to platinum-based chemotherapy.

To analyze the clinical characteristics, survival and prognosis of breast cancer patients under 30 years of age.129 breast cancer patients under 30 years treated from Jan 1980 to May 2000 were retrospectively reviewed. Clinical features, survival and prognostic factors were analyzed by SPSS 10.0 statistic software.Breast cancer patients under 30 years accounted for 2.6% of all breast cancers in our hospital. The overall 5- and 10-year survival rates were 61.5% and 46.7%, respectively. For patients with tumoror = 3 cm or3 cm, the 10-year survival rates were 65.5% and 27.4% (P0.01). For those with number of positive axillary lymph nodes 0, 1-3, oror = 4, the 10-year survival rates were 79.5%, 40.9% or 31.4% (P0.01). For patients who had been treated with or without tamoxifen, the 10-year survival rates were 63.7% and 45% (P0.01). For those complicated with pregnancy and lactation which was found in 24.8% of such patients, the 10-year survival rate was 44.3%. In the multivariate analysis, independent prognostic factors that might improve the overall survival were tumor size, axillary metastatic status and tamoxifen treatment.Breast cancer patients aged 30 years and younger may have good prognosis if multimodality treatment is given. Tumor size, axillary metastatic status and tamoxifen treatment are independent prognostic factors. Prognosis of patients, either complicated with pregnancy and lactation or not, is quite similar if the clinical stage is the same and if being treated by the combined therapy.

DNA repair capacity correlated with sensitivity of cancer cells towards platin-based chemotherapy. This study examined the association between genetic polymorphisms of DNA repair gene XRCC1 and response to cisplatin- or carboplatin-based chemotherapy of advanced non-small cell lung cancer (NSCLC).Totally 105 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XRCC1 genotypes were determined by PCR-RFLP methods using DNA samples isolated from peripheral blood collected before treatment. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression.The response rate to the chemotherapy in patients with the 194Arg/Trp or Trp/Trp genotype significantly higher than that in patients with the Arg/Arg genotype (43.1% vs. 20.3%;OR=2.97,95% CI=1.15-7.72;P0.05). The response rate to chemotherapy was also significantly higher in patients with the 399Arg/Arg genotype than that in patient with the Arg/Gln or Gln/Gln genotype (41.5% vs. 21.2%;OR=2.65,95% CI=1.03-6.87;P0.05).Furthermore, it appeared that 194Arg/Trp and 399Arg/Arg genotypes had synergic effect on the chemotherapy efficacy. Patients with both of these two polymorphisms had a response rate of 66.7% which was significantly greater than that in patients with other genotypes (response rate ranging from 20.0% to 23.1%, P0.001).Polymorphisms in the XRCC1 gene may have significant impact on the response of NSCLC patients to platin-based chemotherapy.

To investigate the expression of microRNA-155 (miRNA-155) in the livers of mice with lipopolysaccharide (LPS)-induced sepsis and to determine the role of dexamethasone (DXM) in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. Moreover, DXM alone inhibited the expression of miRNA-155 to below the baseline level, but did not impact the expression of inflammatory factors, suggesting that the down-regulation of miRNA-155 by DXM may partially, but not completely, depend on the suppression of pro-inflammatory cytokines by DXM. Our data indicate that the overexpression of miRNA-155 in the livers of mice with LPS-induced sepsis may play an important role in the pathological processes of sepsis and that the down-regulation of miRNA-155 by DXM may be a novel mechanism regulating inflammation and immunity.

Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human tumor cells and tumors to cytotoxic molecules. The aim of this pilot study was to investigate the efficacy of PPI in improving the clinical outcome of docetaxel + cisplatin regimen in patients with metastatic breast cancer (MBC).Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2) on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate.Ninety-four patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, B and C were 46.9, 71.0, and 64.5 %, respectively. Median TTP for arm A (n = 32), B (n = 31), C (n = 31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was observed between patients who had taken PPI and who not with ORR (67.7 % vs. 46.9 %, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p = 0.045) [corrected]. Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively (p = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity was observed with PPI.The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial.Clinicaltrials.gov identifier: NCT01069081 .

Background Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. Methods 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. Results In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. Conclusions SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype.