UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1.

The transition of oxidized 5-methylcytosine (5mC) intermediates into the base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that fails to rescue Uhrf1-/- phenotype, is physically and functionally associated with BER complex. We show that UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1. This nonproteolytic action stimulates XRCC1's interaction with the ubiquitin binding domain-bearing RAD23B, leading to the incorporation of TDG into BER complex. Integrative epigenomic analysis in mouse embryonic stem cells reveals that Uhrf2-fostered TDG-RAD23B-BER complex is functionally linked to the completion of DNA demethylation at active promoters and that Uhrf2 ablation impedes DNA demethylation on latent enhancers that undergo poised-to-active transition during neuronal commitment. Together, these observations highlight an essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

Exosomal transfer of miR-195-5p restrains lung adenocarcinoma progression.

Exosome is an important way for tumor cells to communicate with other cells and plays an important role in tumor progression. Previous studies revealed that miR-195-5p acts as a tumor suppressor in lung cancer. However, the role and molecular mechanism of exosomal transferred miR-195-5p in lung adenocarcinoma (LAC) remains unknown. Here, we found that miR-195-5p expression in circulating exosomes of LAC patients was lower than that of healthy controls. Meanwhile, the expression of exosomal miR-195-5p from normal bronchial epithelial cell line BEAS-2B cells was significantly higher than that of lung cancer cell lines. The exosome labeling assay confirmed that BEAS-2B cells-derived exosomes could be captured by lung cancer cells. Furthermore, exosomal miR-195-5p derived from BEAS-2B cells remarkably inhibited the proliferation, migration, invasion of lung cancer cells, and tumor growth in vivo. In addition, exosomal miR-195-5p from BEAS-2B cells also suppressed the tube-forming ability of vascular endothelial cells. Moreover, we verified that miR-195-5p decreased apelin (APLN) expression to inactivate the Wnt signaling pathway, thereby inhibiting tumor invasiveness and angiogenesis. In conclusion, our research shows that exosomal miR-195-5p from normal bronchial epithelial cells hinders the progression of LAC, suggesting that regulation of exosomal miR-195-5p provides a novel strategy for LAC treatment.

circRNA-CPA4 Regulates Cell Proliferation and Apoptosis of Non-small Cell Lung Cancer via the miR-1183/PDPK1 Axis.

Non-small-cell lung cancer (NSCLC) stands as a prevalent subtype of lung cancer, with circular RNAs emerging as key players in cancer development. This study elucidates the role of circRNA-CPA4 in NSCLC. Elevated circRNA-CPA4 expression in NSCLC lines was confirmed through qRT-PCR. Silencing circRNA-CPA4 with shRNA revealed, through CCK-8, colony formation, and flow cytometry assays, a notable constraint on proliferation and promotion of apoptosis in NSCLC cells. Subcellular localization analysis, RNA immunoprecipitation, and expression level assessments were employed to decipher the intricate interplay among miR-1183, circRNA-CPA4, and PDPK1. Results demonstrated heightened circRNA-CPA4 levels in NSCLC, and its knockdown curtailed NSCLC growth in vivo. Acting as a molecular sponge for miR-1183, circRNA-CPA4 regulated PDPK1 expression. Conversely, inhibiting miR-1183 counteracted the impact of circRNA-CPA4 silencing, reinstating NSCLC cell proliferation, and impeding apoptosis. Overall, this study unveils a novel mechanism: circRNA-CPA4 promotes PDPK1 expression by sequestering miR-1183, fostering NSCLC cell proliferation, and hindering apoptosis.

Exposure to smoky coal combustion emissions and leukocyte Alu retroelement copy number.

Household air pollution (HAP) from indoor combustion of solid fuel is a global health burden that has been linked to multiple diseases including lung cancer. In Xuanwei, China, lung cancer rate for non-smoking women is among the highest in the world and largely attributed to high levels of polycyclic aromatic hydrocarbons (PAHs) that are produced from combustion of smoky (bituminous) coal. Alu retroelements, repetitive mobile DNA sequences that can somatically multiply and promote genomic instability have been associated with risk of lung cancer and diesel engine exhaust exposure. We conducted analyses for 160 non-smoking women in an exposure assessment study in Xuanwei, China with a repeat sample from 49 subjects. Quantitative PCR was used to measure Alu repeat copy number relative to albumin gene copy number (Alu/ALB ratio). Associations between clusters derived from predicted levels of 43 HAP constituents, 5-methylchrysene (5-MC), a PAH previously associated with lung cancer in Xuanwei and was selected a priori for analysis, and Alu repeats were analyzed using generalized estimating equations. A cluster of 31 PAHs reflecting current exposure was associated with increased Alu copy number (ß:0.03 per standard deviation change; 95% confidence interval (CI):0.01,0.04; P-value = 2E-04). One compound within this cluster, 5-MC, was also associated with increased Alu copy number (P-value = 0.02). Our findings suggest that exposure to PAHs due to indoor smoky coal combustion may contribute to genomic instability. Additionally, our study provides further support for 5-MC as a prominent carcinogenic component of smoky coal emissions. Further studies are needed to replicate our findings.

Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma.

OBJECTIVE: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response. METHODS: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases. In addition, the model-building genes were identified from 1441 LICMGs by Cox-regression analysis, and a LA immune difference score (LIDscore) was developed to quantify individual differences in each patient, thereby predicting prognosis and susceptibility to immunotherapy and chemotherapy of LA patients. RESULTS: Patients of the GSE72094 cohort were divided into two distinct molecular subtypes based on LICMGs: immune activating subtype (Cluster-C1) and metabolically activating subtype (cluster-C2). The two molecular subtypes have distinct characteristics regarding prognosis, clinicopathology, genomics, immune microenvironment, and response to immunotherapy. Among the LICMGs, LGR4, GOLM1, CYP24A1, SFTPB, COL1A1, HLA-DQA1, MS4A7, PPARG, and IL7R were enrolled to construct a LIDscore model. Low-LIDscore patients had a higher survival rate due to abundant immune cell infiltration, activated immunity, and lower genetic variation, but probably the higher levels of Treg cells in the immune microenvironment lead to immune cell dysfunction and promote tumor immune escape, thus decreasing the responsiveness to immunotherapy compared with that of the high-LIDscore patients. Overall, high-LIDscore patients had a higher responsiveness to immunotherapy and a higher sensitivity to chemotherapy than the low-LIDscore group. CONCLUSIONS: Molecular subtypes based on LICMGs provided a promising strategy for predicting patient prognosis, biological characteristics, and immune microenvironment features. In addition, they helped identify the patients most likely to benefit from immunotherapy and chemotherapy.

Temporal trends and projections of gynecological cancers in China, 2007-2030.

BACKGROUND: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China. METHODS: We extracted age-specific rate of cancer cases and deaths during 2007-2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007-2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1). RESULTS: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7-4.3%) during 2007-2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3-4.9%), 3.3% (95% CI: 2.6-4.1%), 2.4% (95% CI: 1.4-3.5%), 4.4% (95% CI: 2.5-6.4%), and 3.6% (95% CI: 1.4-5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007-2030, except that uterine cancer deaths and mortality were declined. CONCLUSIONS: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned.

Evaluation of surgical outcomes and prognostic factors of second primary lung cancer based on a systematic review and meta-analysis.

BACKGROUND: Although surgery has been widely applied for SPLC therapy, there is still no uniform treatment approach. Whether SPLC and primary lung cancer have similar prognostic characteristics remains controversial. Herein, based on a systematic review and meta-analysis, we aimed to enucleate the influences of diverse surgical strategies and underlying prognostic factors on the prognosis of patients with both the first primary lung cancer and SPLC underwent surgical resection. METHODS: A comprehensive and systematic literature search was implemented in three databases (MEDLINE, EMBASE, and Cochrane), and eligible studies were screened following inclusion and exclusion criteria. Meanwhile, we extracted the hazard ratios (HR) together with 95% confidence intervals (CI) for each prognostic factor, either directly or indirectly, from the enrolled literature. RESULTS: Eleven studies (published between 2000 and 2022) were included in this study, including 1,131 SPLC patients. The overall survival (OS) exhibited no difference between patients with lobectomy and sublobar resection after SPLC (HR: 0.87, 95%CI: 0.62-1.21, P = 0.41). The patients after completion pneumonectomy had a poor prognosis (HR: 1.85, 95% CI: 1.34-2.55, P < 0.01). Poor prognostic factors after SPLC surgery included synchronous SPLC (HR: 3.38, 95%CI: 1.53-7.46, P < 0.01), tumor diameter > 2 cm (HR: 2.44, 95%CI: 1.73-3.44, P < 0.01), solid predominant in CT morphology (HR: 3.08, 95% CI: 1.14-8.33, P = 0.03), lymph node metastasis (HR: 2.79, 95%CI: 1.40-5.56), and smoking (HR: 2.37, 95%CI: 1.08-26.82, P < 0.01). Tumor disease-free interval (DFI), tumor histological type, and gender had no impact on the prognosis of patients received SPLC surgery. CONCLUSIONS: Patients with SPLC, especially those with poor cardiopulmonary function reserve, should be prioritized for sublobar resection for treatment. These patients should also try to avoid completion pneumonectomy. Patients with synchronous SPLC, tumor diameter > 2 cm, solid predominant in CT morphology, lymph node metastasis, and smoking had a poor prognosis. Meanwhile, SPLC has similar prognostic characteristics with single primary lung cancer. However, the study has some limitations and more evidence is warranted to verify the findings.

Biodegradable Nanofibrillated Cellulose/Poly-(butylene adipate-co-terephthalate) Composite Film with Enhanced Barrier Properties for Food Packaging.

Biodegradable composites consisting of Poly-(butylene adipate-co-terephthalate) (PBAT), thermoplastic starch, hydrophobically modified nanofibrillated cellulose (HMNC), and green surfactant (sucrose fatty acid ester) were prepared via the melt-mixing and film-blowing process (PBAT-HMNC). The composites were characterized using the Fourier transform infrared spectroscope (FT-IR), scanning electron microscope (SEM), and thermogravimetric analyzer (TGA). The mechanical and barrier properties were systematically studied. The results indicated that PBAT-HMNC composites exhibited excellent mechanical and barrier properties. The tensile strength reached the maximum value (over 13 MPa) when the HMNC content was 0.6% and the thermal decomposition temperature decreased by 1 to 2 °C. The lowest values of the water vapor transmission rate (WVTR) and the oxygen transmission rate (OTR) were obtained from the composite with 0.6 wt% HMNC, prepared via the film-bowing process with the values of 389 g/(m2·day) and 782 cc/(m2·day), which decreased by 51.3% and 42.1%, respectively. The Agaricus mushrooms still had a commodity value after 11 days of preservation using the film with 0.6 wt% HMNC. PBAT-HMNC composites have been proven to be promising nanocomposite materials for packaging.

On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial.

BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. METHODS: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. RESULTS: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. CONCLUSION: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03668496.

Serum cholinesterase may independently predict prognosis in non-small-cell lung cancer.

BACKGROUND: Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients. METHODS: A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients. RESULTS: The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67-0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR < 2.95, HR: 0.71, 95% CI: 0.56-0.89, p = 0.003), of adenocarcinoma (HR: 0.66, 95% CI: 0.54-0.80, p < 0.001), in advanced stage (HR: 0.77, 95% CI: 0.66-0.92, p < 0.01), and received chemotherapy (HR: 0.75, 95% CI: 0.59-0.96, p < 0.02). CONCLUSION: Baseline ChE may have independent prognostic value for NSCLC patients. Longitudinal studies should be performed to corroborate this finding.

The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma.

N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.

AFF4 facilitates melanoma cell progression by regulating c-Jun activity.

Melanoma is characterized by high mortality and poor prognosis due to metastasis. AFF4 (AF4/FMR2 family member 4), as a scaffold protein, is a component of the super elongation complex (SEC), and is involved in the progression of tumors, e.g., leukemia, head and neck squamous cell carcinoma (HNSCC). However, few studies on AFF4 have focused on melanoma. Here, AFF4 expression levels and clinicopathological features were evaluated in melanoma tissue samples. Then, we performed cell proliferation, migration and invasion assays in A375 and A2058 cells lines in vitro to evaluate the role of AFF4 in melanoma. The effects of AFF4 knockdown in vivo were characterized via a xenograft mouse model. Finally, the correlation between c-Jun and AFF4 protein levels in melanoma was analyzed by rescue assay and immunohistochemistry (IHC). We found that AFF4 expression was upregulated in melanoma tumor tissues and that AFF4 protein expression was also closely related to the prognosis of patients with cutaneous melanoma. Moreover, AFF4 could promote the invasion and migration of melanoma cells by mediating epithelial to mesenchymal transition (EMT). AFF4 might regulate c-Jun activity to promote the invasion and migration of melanoma cells. Importantly, c-Jun was regulated by the AFF4 promoted melanoma tumorigenesis in vivo. Taken together, AFF4 may be a novel oncogene that promotes melanoma progression through regulation of c-Jun activity.

Regulation of circular RNAs act as ceRNA in a hypoxic pulmonary hypertension rat model.

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH.

Dysregulation of ferroptosis may involve in the development of non-small-cell lung cancer in Xuanwei area.

The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non-small-cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para-carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up-regulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Research on the effect of TiO2 nanotubes coated by gallium nitrate on Staphylococcus aureus-Escherichia coli biofilm formation.

BACKGROUND: In clinical practice, the cases with bacterial infection caused by titanium implants and bacterial biofilm formation on the surface of titanium materials implanted into human body can often be observed. Thus, this study aimed to demonstrate whether the mixed biofilm of Staphylococcus aureus/Escherichia coli can be formed on the surface of titanium material through in vitro experiments and its formation rules. METHODS: The titanium plates were put into the well containing S aureus or/and E coli. Bacterial adhesion and biofilm formation were analyzed by crystal violet, XTT method, confocal laser scanning microscopy, and scanning electron microscopy. RESULTS: The results of bacterial adhesion in each group at 6-72 hours showed that the number of bacterial adhesion in each group was increased with the extension of time and reached to the highest level at 72 hours. Moreover, the biofilm structure in the S aureus-E coli group was significantly more complex than that of the simple S aureus group or E coli group, and the number of bacteria was also significantly increased in the S aureus-E coli group. CONCLUSION: Those data provide a laboratory basis for the prevention and treatment of mixed infection of subsequent biological materials.

Study on the Effects of Estradiol in Staphylococcus epidermidis Device-Related Capsule Formation.

BACKGROUND: Capsular contracture, mainly caused by Staphylococcus epidermidis (S. epidermidis) biofilm formation, is a complex problem for breast cancer patients who undergo surgical prosthetic breast reconstruction. Estradiol has been reported to be involved in the formation of bacterial biofilms. Thus, the underlying mechanism of estradiol in capsular contracture needs to be investigated. METHODS: Biofilm-related gene expressions were measured by qRT-PCR after sterilizing the silicone with bacterial suspension and E2 treatment in vitro. Rat models were established with bilateral ovariectomy operations and estradiol subcutaneous injections. The effects of estradiol on capsular contracture were detected by monitoring serum estradiol levels, bacterial infection rate in organs, biofilm formation and capsular contracture in vivo; inflammatory factors in vivo were examined as well. Biofilm on the silicone implants was observed under a scanning electron microscope. RESULTS: Both positive regulatory genes and negative regulatory genes were increased by the high concentration of estradiol, suggesting that estradiol can promote the formation of biofilm by not only positive but also negative regulations. High estradiol levels increased bacterial infection rate in organs, biofilm formation and capsular contracture. Further, high estradiol caused a large number of inflammatory cells to infiltrate and caused serious inflammatory reactions that aggravate the immune imbalances of the host. CONCLUSION: High estradiol levels contribute to increasing capsular contracture caused by S. epidermidis biofilm formation. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Gene polymorphisms of SFTPB rs7316, rs9752 and PAOX rs1046175 affect the diagnostic value of plasma Pro-SFTPB and DAS in Chinese Han non-small-cell lung cancer patients.

Plasma pro-surfactant protein B (pro-SFTPB) and N1,N12-diacetylspermine (DAS) can be used as markers for the diagnosis of non-small-cell lung carcinoma (NSCLC). Whether the genetic diversity affects the application value of Pro-SFTPB and DAS as a diagnostic marker for NSCLC is still unknown. This study aims to explore the relationship between SFTPB rs7316, rs9752 and PAOX rs1046175 gene polymorphisms and the diagnostic value of plasma Pro-SFTPB and DAS in patients with Chinese Han lung cancer. SFTPB rs7316, rs9752 and PAOX rs1046175 genotypes were analyzed by direct sequencing in 425 patients with NSCLC and 425 controls, and the levels of Pro-SFTPB and DAS in plasma were determined by enzyme-linked immunosorbent assay (ELISA). The area under the curve (AUC) of the SFTPB rs7316 locus TT genotype for the diagnosis of NSCLC was 0.758, and the AUC of the TC/CC genotype for the diagnosis of NSCLC was 0.872. The AUC of the SFTPB rs9752 locus GG genotype for the diagnosis of NSCLC was 0.935, and the AUC of the GC/CC genotype for the diagnosis of NSCLC was 0.648. The AUC of the PAOX rs1046175 locus GG for the diagnosis of NSCLC was 0.669, and the AUC of the GC/CC genotype for the diagnosis of NSCLC was 0.749. In conclusion, SFTPB rs7316, rs9752, and PAOX rs1046175 gene polymorphisms affect the diagnostic value of plasma Pro-SFTPB and DAS in patients with Chinese Han NSCLC.

Lung cancer risk by geologic coal deposits: A case-control study of female never-smokers from Xuanwei and Fuyuan, China.

Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never-smokers due to use of bituminous ("smoky") coal for heating and cooking. We conducted a population-based case-control study of 1031 lung cancer cases and 493 controls among never-smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit (p = 7.8E-05). Compared to non-smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43-16.38) to OR = 33.40 (95% CI: 13.07-85.34). Further, women born into homes that used smoky coal and subsequently changed to non-smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61-25.46)) than women born into homes that used non-smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03-11.04, pdifference = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early-life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.