miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma.

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

[Mechanism of traditional Chinese medicine in treating ulcerative colitis-related colorectal cancer by regulating NF-κB-related signaling pathways: a review].

Ulcerative colitis is a chronic, recurrent, and nonspecific intestinal inflammatory disease, which is difficult to cure and has the risk of deterioration into related tumors. Long-term chronic inflammatory stimulation can increase the risk of cancerization. With the signaling pathway as a key link in the regulation of tumor microenvironments, nuclear factor-kappa B(NF-κB) is an important regulator of intestinal inflammation. It can also be co-regulated as downstream factors of other signaling pathways, such as TLR4, MAPK, STAT, PI3K, and so on. At present, a large number of animal experiments have proved that traditional Chinese medicine(TCM) can reduce inflammation by interfering with NF-κB-related signaling pathways, improve intestinal inflammation, and inhibit the progression of inflammation to tumors. This article reviewed the relationship between NF-κB-related signaling pathways and the intervention mechanism of TCM, so as to provide a reference for the clinical treatment of ulcerative colitis and the optimization of related cancer prevention strategies.

Transarterial chemoembolization plus camrelizumab is an effective and tolerable bridging therapy for patients with intermediate­stage hepatocellular carcinoma: A pilot study.

Transarterial chemoembolization (TACE) has been reported to synergize with camrelizumab in the treatment of hepatocellular carcinoma (HCC). The present study aimed to explore the potential of TACE and camrelizumab as a bridging therapy prior to surgery for patients with HCC. For this purpose, 11 patients with HCC with intermediate stage disease [classified by China Liver Cancer (CNLC) staging] who received TACE combined with camrelizumab as a bridging therapy prior to surgery were enrolled in this study. The treatment response was evaluated at 2 weeks following TACE therapy and following camrelizumab treatment. The relapse-free survival (RFS) and overall survival (OS) of the patients were calculated. The objective response and disease control rates were 72.7 and 100.0% following TACE treatment, and were 100.0 and 100.0% following camrelizumab treatment, respectively. The α-fetoprotein levels gradually decreased following TACE, camrelizumab treatment and surgical resection (all P<0.05). Of note, the CNLC stage decreased following treatment (P=0.007) and the downstaging success rate was 63.6%. In terms of survival profiles, the mean RFS (95% CI) was 14.1 (11.7-16.5) months and the 1-year RFS rate was 77.9±14.1%. Furthermore, the mean OS (95% CI) was 15.0 (13.2-16.8) months and the 1-year OS rate was 80.0±17.9%. Successful downstaging was associated with RFS (P=0.041), but not OS (P=0.221). With regard to safety, 6 (54.5%) patients experienced reactive cutaneous capillary endothelial proliferation, 5 (45.5%) patients reported pain and 4 (36.4%) patients had a fever. On the whole, the present study demonstrated that TACE plus camrelizumab may be an effective and safe strategy that has potential for use as a bridging strategy prior to surgery in patients with intermediate-stage HCC.

Inhibition of TMEM16A improves cisplatin-induced acute kidney injury via preventing DRP1-mediated mitochondrial fission.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca2+-activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown. In this study, we established cisplatin AKI mice model and found that TMEM16A expression was upregulated in the injured kidney. In vivo knockdown of TMEM16A effectively prevented cisplatin-induced tubular cell apoptosis, inflammation and kidney function loss. Western blot and transmission electron microscopy (TEM) revealed that TMEM16A knockdown inhibited Drp1 translocation from the cytoplasm to mitochondria and prevented mitochondrial fission in tubular cells. Consistently, in cultured HK2 cells, knockdown or inhibition of TMEM16A by shRNA or its specific inhibitor suppressed cisplatin-induced mitochondrial fission and its associated energy dysfunction, ROS accumulation, and cell apoptosis via inhibiting Drp1 activation. Further investigation showed that genetic knockdown or pharmacological inhibition of TMEM16A inhibited cisplatin-induced Drp1 Ser-616 site phosphorylation through ERK1/2 signaling pathway, whereas overexpression of TMEM16A promoted this effect. Treatment with Drp1 or ERK1/2 inhibitor could efficiently prevent cisplatin-induced mitochondrial fission. Collectively, our data suggest that TMEM16A inhibition alleviated cisplatin-induced AKI by preventing tubular cell mitochondrial fission through the ERK1/2 / Drp1 pathway. Inhibition of TMEM16A may be a novel therapeutic strategy for AKI.

Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity.

Sex is known to be an important factor in the incidence, progression, and outcome of cancer. A better understanding of the underlying mechanisms could help improve cancer prevention and treatment. Here, we demonstrated a crucial role of antitumor immunity in the sex differences in cancer. Consistent with observations in human cancers, male mice showed accelerated tumor progression compared with females, but these differences were not observed in immunodeficient mice. Androgen signaling suppressed T-cell immunity against cancer in males. Mechanistically, androgen-activated androgen receptor upregulated expression of USP18, which inhibited TAK1 phosphorylation and the subsequent activation of NF-κB in antitumor T cells. Reduction of testosterone synthesis by surgical castration or using the small-molecular inhibitor abiraterone significantly enhanced the antitumor activity of T cells in male mice and improved the efficacy of anti-PD-1 immunotherapy. Together, this study revealed a novel mechanism contributing to sex differences in cancer. These results indicate that inhibition of androgen signaling is a promising approach to improve the efficacy of immunotherapy in males. SIGNIFICANCE: Androgen signaling induces immunosuppression in cancer by blocking T-cell activity through upregulation of USP18 and subsequent inhibition of NF-κB activity, providing a targetable axis to improve antitumor immunity in males.

TSA-SCC: Text Semantic-Aware Screen Content Coding With Ultra Low Bitrate.

Due to the rapid growth of web conferences, remote screen sharing, and online games, screen content has become an important type of internet media information and over 90% of online media interactions are screen based. Meanwhile, as the main component in the screen content, textual information averagely takes up over 40% of the whole image on various commonly used screen content datasets. However, it is difficult to compress the textual information by using the traditional coding schemes as HEVC, which assumes strong spatial and temporal correlations within the image/video. State-of-the-art screen content coding (SCC) standard as HEVC-SCC still adopts a block-based coding framework and does not consider the text semantics for compression, thus inevitably blurring texts at a lower bitrate. In this paper, we propose a general text semantic-aware screen content coding scheme (TSA-SCC) for ultra low bitrate setting. This method detects the abrupt picture in a screen content video (or image), recognizes textual information (including word, position, font type, font size and font color) in the abrupt picture based on neural networks, and encodes texts with text coding tools. The other pictures as well as the background image after removing texts from the abrupt picture via inpainting, are encoded with HEVC-SCC. Compared with HEVC-SCC, the proposed method TSA-SCC reduces bitrate by up to 3× at a similar compression quality. Moreover, TSA-SCC achieves much better visual quality with less bitrate consumption when encoding the screen content video/image at ultra low bitrates.

Blockade of TMEM16A protects against renal fibrosis by reducing intracellular Cl- concentration.

BACKGROUND AND PURPOSE: Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a Ca2+ -activated chloride channel, contributes to the progression of renal fibrosis. EXPERIMENTAL APPROACH: Masson staining, western blot and immunohistochemistry were used to measure renal fibrosis and related proteins expression. MQAE was used to evaluate the intracellular Cl- concentration. KEY RESULTS: TMEM16A expression was significantly up-regulated in fibrotic kidneys of unilateral ureteral obstruction (UUO) and high-fat diet murine models and in renal samples of IgA nephropathy patients. In vivo knockdown of TMEM16A with adenovirus harbouring TMEM16A-shRNA or inhibition of TMEM16A channel activity with inhibitors CaCCinh-A01 or T16Ainh-A01 effectively prevented UUO-induced renal fibrosis and decreased protein expression of fibronectin, α-SMA and collagen in the obstructed kidneys. In cultured HK2 cells, knockdown or inhibition of TMEM16A suppressed TGF-ß1-induced epithelial-mesenchymal transition, reduced snail1 expression and phosphorylation of Smad2/3 and ERK1/2, whereas overexpression of TMEM16A showed the opposite effects. TGF-ß1 increased [Cl- ]i in HK2 cells, which was inhibited by knockdown or inhibition of TMEM16A. Reducing [Cl- ]i significantly blunted TGF-ß1-induced Smad2/3 phosphorylation and profibrotic factors expression. The profibrotic effects of TGF-ß1 were also reduced by inhibition of serum- and glucocorticoid-inducible protein kinase 1 (SGK1). SGK1 was also suppressed by reducing [Cl- ]i. CONCLUSION AND IMPLICATIONS: Blockade of TMEM16A prevented the progression of kidney fibrosis, likely by suppressing [Cl- ]i/SGK1/TGF-ß1 signalling pathway. TMEM16A may be a potential new therapeutic target against renal fibrosis.

[Designment and application of a novel device for microcirculation viviperception].

The key technology of the device for the viviperception of the animal mesenteric microcirculation is to simulate the celiac environment in the device. The technical requirements of the device for microcirculation viviperception are that the observation box should be able to "keep warm, preserve moisture, continually perfuse, and fix the sample"; and the lighting should be "intense", "convergence", and "cool". After actual application, it was found that the newly designed and developed the device by research personnel of Wannan Medical College for the viviperception of the animal mesenteric microcirculation can meet the technical requirements, which is able to "keep warm, preserve moisture, continually perfuse, and fix the sample", and using LED lamp as the microscope light source is "intense", "convergence", and "cool". This device is ingenious and reasonable in design, stable in technology, convenient in operation, and competent in microcirculation viviperception. It solves the technical problem to simulate the celiac environment for mesenteric microcirculation viviperception. The device provides convenience to observe and study the microcirculation, which is worth to be applicated widely.

Prediction of Risk Factors for the Evolution of Traumatic Subdural Effusion into Chronic Subdural Hematoma.

PURPOSE: To explore the risk factors of the evolution of traumatic subdural effusion (TSE) into chronic subdural hematoma (CSDH). MATERIALS AND METHODS: The 70 patients' gender, age, location of effusion, unilateral and bilateral, Glasgow coma score (GCS) at admission, presence or absence of brain contusion, the time of effusion appeared, daily amount of mannitol, mannitol number of days used, with or without atorvastatin calcium tablets, with or without antiplatelet aggregation drugs, with or without anticoagulant drugs, with or without abnormalities in blood coagulation routines, computed tomography (CT) layer height, the thickness, and CT value of the first effusion were analyzed by single factor. Logistic multivariate regression analysis was performed on the statistically significant indicators. Power of the regression model was evaluated using receiver operating characteristic (ROC) curve. RESULTS: Univariate analysis showed that the presence or absence of brain contusion, the time of effusion appeared, atorvastatin calcium tablets use or not, the CT value of the effusion, and TSE into CSDH evolution varied significantly compared to the non-evolved group (P<0.05). Logistic multivariate regression analysis showed that combined brain contusion (odds ratio (OR)=16.247, 95% confidence interval (CI), 1.831-144.157, P = 0.012), early onset of effusion (OR = 0.573, 95% CI: 0.349-0.941, P = 0.028), atorvastatin calcium tablets not used after effusion (OR = 60.028, 95% CI: 6.103-590.399, P = 0.0001), and high CT value (OR = 1.285, 95% CI: 1.067-1.547, P = 0.008) were risk factors for the evolution of TSE into CSDH. The ROC model suggested that the prediction of these risk factors had high diagnostic accuracy. CONCLUSION: TSE patients with brain contusion, early onset of effusion, without the usage of atorvastatin calcium tablets after effusion, and high CT value of the first effusion are at a risk of evolving into CSDH.

Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis.

BACKGROUND: Glioma is the most common primary malignant tumor with poor prognosis due to the lack of understanding the mechanism underlying the disease and the early diagnosis indexs. It is necessary to identify molecular signatures for predicting the overall prognosis of glioma. Adipocyte enhancer binding protein1 (AEBP1) acts as a transcriptional repressor and plays a role in adipogenesis and smooth muscle cell differentiation. However, its role in glioma remains unclear. MATERIALS AND METHODS: AEBP1 expression was analyzed by bioinformatics using the public database and by qPCR and western blotting in human glioma tissues. AEBP1 downregulation was performed by lipofectamine3000-mediated siRNA transfection. Cell proliferation and invasion were determined by cell counting kit-8 and transwell assays, while early cell apoptosis was determined by flow cytometry. The proteins of downstream NF-κB signaling pathway were determined by western blotting. RESULTS: AEBP1 is highly expressed in human gliomas. Lipofectamine 3000-mediated siRNA transfection stably and efficiently suppressed AEBP1 mRNA and protein expression in human glioma cells. AEBP1 downregulation inhibited cell proliferation and invasion, but promoted early cell apoptosis. Also, AEBP1 knockdown in glioma cells decreased the expression of NF-κB1. Furthermore, the downstream of NF-κB signaling pathway, Bax, caspase-3 are increased, while MMP2 and Bcl-2 are decreased in glioma cells. CONCLUSION: Elevated AEBP1 is positively associated with poor prognosis of glioma. AEBP1 downregulation suppressed cell proliferation and invasion, but promoted early cell apoptosis. AEBP1 downregulation suppressed the cell proliferation and invasion may by inhibiting the NF-κB signaling pathway.

ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling.

BACKGROUND: Endothelial progenitor cell (EPC) therapy has been suggested as a major breakthrough in the treatment of ischemic diseases. However, the molecular mechanism that underlies EPC functional regulation is still unclear. METHODS: We examined the angiogenic capacity of EPCs in a hindlimb ischemia model of wild-type and ClC-3 knockout mice. RESULTS: Mice lacking of ClC-3 exhibited reduced blood flow recovery and neovascularization in ischemic muscles 7 and 14 days after hind limb ischemia. Moreover, compared with wild-type EPCs, the hindlimb blood reperfusion in mice receiving ClC-3 knockout EPCs was significantly impaired, accompanied by reduced EPC homing and retention. In vitro, EPCs derived from ClC-3 knockout mice displayed impaired migratory, adhesive, and angiogenic activity. CXC chemokine receptor 4 (CXCR4) expression was significantly reduced in EPC from ClC-3 knockout mice compared with wild-type. Moreover, the expression and phosphorylation of Janus kinase 2 (JAK-2), a downstream signalling of CXCR4, was also reduced in ClC-3 knockout EPC, indicating that CXCR4/JAK-2 signalling is dysregulated by ClC-3 deficiency. Consistent with this assumption, the migratory capacity of wild-type EPCs was attenuated by either CXCR4 antagonist AMD3100 or JAK-2 inhibitor AG490. More importantly, the impaired migratory capacity of ClC-3 knockout EPCs was rescued by overexpression of CXCR4. CONCLUSIONS: ClC-3 plays a critical role in the angiogenic capacity of EPCs and EPC-mediated neovascularization of ischemic tissues. Disturbance of CXCR4/JAK-2 signalling may contribute to the functional impairment of ClC-3 deficient EPCs. Thus, ClC-3 may be a potential therapeutic target for modulating neovascularization in ischemic diseases.

Lentivirus mediated γ-interferon-inducible lysosomal thiol reductase (GILT) knockdown suppresses human glioma U373MG cell proliferation.

BACKGROUND: Glioma is the most common malignancy in brain carcinoma with poor prognosis due to the lack of understanding of the mechanism underlying the disease. γ-interferon-inducible lysosomal thiol reductase (GILT) plays a critical role in the process of antigen processing. However, the role of GILT in the tumorigenesis of glioma remains unknown. MATERIALS AND METHODS: The expression of GILT was analyzed by bioinformatics using the public database and by qPCR in three human glioma cell lines. Cell growth and viability were determined by Celigo and MTT assays, while cell cycle arrest and apoptosis were determined using flow cytometry. Giemsa staining was used to analyze the colony formation, while cell motility was assessed using transwell migration and invasion assays, as well as, using tumor growth in nude mice. RESULTS: GILT was highly expressed as observed in the public database on human gliomas and two human glioma cell lines, U373MG and U87MG cells. The downregulation of GILT by lentiviral-mediated silencing inhibits the cell growth, colony formation, and migration but promotes apoptosis and results in cell cycle arrest at the G0/G1 phase in the U373MG cells. Also, the knockdown of GILT inhibits tumor growth in vivo. CONCLUSION: Elevated GILT is positively associated with glioma progression. GILT silencing suppresses cell proliferation, colony formation, migration, and tumor growth, and induces apoptosis and cell cycle arrest. GILT may serve as a potential target for the treatment of glioma.

Lycopene attenuates LPS-induced liver injury by inactivation of NF-κB/COX-2 signaling.

AIM: This study aimed to investigate the effect of lycopene on LPS-induced liver injury in mice and its mechanisms. METHODS: Male C57bl/6 mice were randomly assigned to three groups: sham control group (S-C), LPS control group (L-C), lycopene treatment group (L-T). The mice from the L-T were treated with lycopene for 2 weeks, and the remaining mice with solvent. Afterwards, the mice from the L-C and the L-T received an intraperitoneal injection of LPS (20 mg/kg, dissolved in sterile saline), and the S-C mice were injected with sterile saline. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were determined for analysis of liver function. Levels of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-6, malondialdehyde (MDA) content, and the activity of superoxide dismutase (SOD), were detected in serum. Liver tissues were operated for morphologic analysis and determination of protein by western blot. RESULTS: Pretreatment with lycopene significantly decreased levels of ALT, AST, and TNF-α and IL-6, reduced MDA content, and increased activity of SOD in serum compared with the L-C mice. Lycopene increased expression of nuclear factor-erythroid 2 related factor 2 (Nrf2), and reduced expression of cyclooxygenase (COX)-2, and phosphorylation of nuclear factor-kappa B (NF-κB) and extracellular regulated protein kinases 1/2 (ERK1/2). CONCLUSION: The results showed that lycopene attenuates LPS-induced liver injury by reducing NF-κB/COX-2 signaling by upregulation of Nrf2/HO-1 activation.

ClC-3 promotes angiotensin II-induced reactive oxygen species production in endothelial cells by facilitating Nox2 NADPH oxidase complex formation.

Recent evidence suggests that ClC-3, a member of the ClC family of Cl- channels or Cl-/H+ antiporters, plays a critical role in NADPH oxidase-derived reactive oxygen species (ROS) generation. However, the underling mechanisms remain unclear. In this study we investigated the effects and mechanisms of ClC-3 on NADPH oxidase activation and ROS generation in endothelial cells. Treatment with angiotensin II (Ang II, 1 µmol/L) significantly elevated ClC-3 expression in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, Ang II treatment increased ROS production and NADPH oxidase activity, an effect that could be significantly inhibited by knockdown of ClC-3, and further enhanced by overexpression of ClC-3. SA-ß-galactosidase staining showed that ClC-3 silencing abolished Ang II-induced HUVEC senescence, whereas ClC-3 overexpression caused the opposite effects. We further showed that Ang II treatment increased the translocation of p47phox and p67phox from the cytosol to membrane, accompanied by elevated Nox2 and p22phox expression, which was significantly attenuated by knockdown of ClC-3 and potentiated by overexpression of ClC-3. Moreover, overexpression of ClC-3 increased Ang II-induced phosphorylation of p47phox and p38 MAPK in HUVECs. Pretreatment with a p38 inhibitor SB203580 abolished ClC-3 overexpression-induced increase in p47phox phosphorylation, as well as NADPH oxidase activity and ROS generation. Our results demonstrate that ClC-3 acts as a positive regulator of Ang II-induced NADPH oxidase activation and ROS production in endothelial cells, possibly via promoting both Nox2/p22phox expression and p38 MAPK-dependent p47phox/p67phox membrane translocation, then increasing Nox2 NADPH oxidase complex formation.

Behavior of Zein in Aqueous Ethanol under Atmospheric Pressure Cold Plasma Treatment.

The effects of atmospheric cold plasma (ACP) on zein in aqueous ethanol (80%, v/v) were investigated including particle size distribution, molecular structure, and content of free sulfhydryl (free-SH) group and disulfide bond, etc. The film-forming properties of zein films were also characterized. After ACP treatment, the particle size of zein aggregates showed a remarkable decrease and uniform particle distribution. There was a downward trend both in pH value and viscosity with the increasing ACP treatment intensity. Moreover, the increase of disulfide bonds concentration was suggested to be correlated to the compact structure strengthened by cross-linking between zein molecules. It was proved from SEM micrographs that plasma could significantly decrease the aggregation degree of zein micelles. There was a slight decrease of the peak intensity in UV and fluorescence spectra compared with native zein, indicating the bulk structure of zein solution had not been disrupted. The reinforced flexibility and tensile strength of zein films had been observed after treatment on film-forming solution. This study provided an experimental basis for the investigation on behavior of plasma-treated protein in solution.

A Two-Stage Protocol With Vacuum Sealing Drainage for the Treatment of Type C Pilon Fractures.

Management of type C pilon fractures remains controversial and challenging. The aim of the present study was to provide a 2-stage protocol with vacuum sealing drainage for the treatment of type C pilon fractures. From March 2009 to March 2012, 16 patients (mean age 42.3 years) were admitted to our department with type C pilon fractures and treated with single-stage external fixation and second-stage internal fixation (anteromedial incision) combined with vacuum sealing drainage. The American Orthopaedic Foot and Ankle Society scale score averaged 86.5 for this group of patients. The range of motion was 30° ± 8.9°. An excellent or good American Orthopaedic Foot and Ankle Society scale score was obtained for all patients. None of the 16 patients developed skin necrosis, nonunion, or fixation failure during the follow-up period. Moreover, the visual analog scale pain scores were 0.7 ± 0.8, 0.9 ± 0.7, and 1.4 ± 1.0 during rest, active movement, and weightbearing, respectively. The postoperative radiographs showed excellent treatment effects. A 2-stage protocol, combined with vacuum sealing drainage, for the treatment of type C pilon fractures can eliminate deep infection and complex surgery and is a simple and effective treatment method. In addition, full exposure of the anteromedial incision, the avoidance of the anterior tibial muscle tendon sheath, and the avoidance of soft tissue injuries are generally recommended in this operation.

The relationship between seven common polymorphisms from five DNA repair genes and the risk for breast cancer in northern Chinese women.

BACKGROUND: Converging evidence supports the central role of DNA damage in progression to breast cancer. We therefore in this study aimed to assess the potential interactions of seven common polymorphisms from five DNA repair genes (XRCC1, XRCC2, XRCC3, XPA and APEX1) in association with breast cancer among Han Chinese women. METHODOLOGY/PRINCIPAL FINDINGS: This was a case-control study involving 606 patients diagnosed with sporadic breast cancer and 633 age- and ethnicity-matched cancer-free controls. The polymerase chain reaction-ligase detection reaction method was used to determine genotypes. All seven polymorphisms were in accordance with Hardy-Weinberg equilibrium in controls. Differences in the genotypes and alleles of XRCC1 gene rs25487 and XPA gene rs1800975 were statistically significant between patients and controls, even after the Bonferroni correction (P<0.05/7). Accordingly, the risk for breast cancer was remarkably increased for rs25487 (OR = 1.28; 95% CI: 1.07-1.51; P = 0.006), but decreased for rs1800975 (OR = 0.77; 95% CI: 0.67-0.90; P = 0.001) under an additive model at a Bonferroni corrected alpha of 0.05/7. Allele combination analysis showed higher frequencies of the most common combination C-G-G-C-G-G-G (alleles in order of rs1799782, rs25487, rs3218536, rs861539, rs1800975, rs1760944 and rs1130409) in controls than in patients (PSim = 0.002). In further interaction analysis, two-locus model including rs1800975 and rs25487 was deemed as the overall best model with the maximal testing accuracy of 0.654 and the cross-validation consistency of 10 out of 10 (P = 0.001). CONCLUSION: Our findings provide clear evidence that XRCC1 gene rs25487 and XPA gene rs1800975 might exert both independent and interactive effects on the development of breast cancer among northern Chinese women.