Evaluation of nocturnal apnea and airflow limitation as indicators for cognitive dysfunction in patients with chronic obstructive pulmonary disease/obstructive sleep apnea hypopnea syndrome overlap syndrome.

OBJECTIVE: The aim of this study is to investigate how much intermittent hypoxemia and airflow limitation contribute to cognitive impairment in overlap syndrome (OS), which is the coexistence of two common diseases, obstructive sleep apnea hypopnea syndrome (OSAHS) and chronic obstructive pulmonary disease (COPD). METHODS: We conducted a cross-sectional study of patients with OSAHS, COPD or OS, compared with normal controls, to determine the association between sleep apnea/pulmonary function-related indicators and cognitive dysfunction in individuals with OSAHS, COPD or OS. RESULTS: A total of 157 participants were recruited. Both OSAHS and OS presented lower adjusted Montreal cognitive assessment (MoCA) scores compared with COPD group. In addition, the MoCA score was significantly lower in COPD group compared with control group. The incidence of cognitive impairment was 57.4% in OSAHS group, and 78% in OS group, which were significantly higher than COPD group (29%) and control group (8.8%). Furthermore, a broader range of cognitive domains were affected in OS group compared with OSAHS group. Elevated levels of oxygen desaturation index (ODI) and/or apnea hypopnea index (AHI) were positively correlated with increased Epworth sleeping scale (ESS) in OSAHS and OS. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) were positively correlated with cognitive scores in OSAHS but not in OS. Serum level of hypoxia-inducible factor-1α (HIF-1α) was significantly higher in OS. Logistic regression identified ODI as an independent risk factor for cognitive impairment in OS, while severity of snoring and PEF were independent risk factors in OSAHS. DISCUSSION: This study revealed significant cognitive impairment in OS, OSAHS and COPD. Sleep-related indicators are warranted in OS patients for detection, differentiation and grading of cognitive impairment, whereas pulmonary functions are warranted in OSAHS patients for detection and early intervention of cognitive impairment.

Selective Stereoretention of Carbohydrates upon C-C Cleavage Enabling D-Glyceric Acid Production with High Optical Purity over a Ag/γ-Al2O3 Catalyst.

Chiral carboxylic acid production from renewable biomass by chemocatalysis is vitally important for reducing our carbon footprint, but remains underdeveloped. We herein establish a strategy that make use of a stereogenic center of biomass to achieve a rare example of D-glyceric acid production with the highest yield (86.8 %) reported to date as well as an excellent ee value (>99 %). Unlike traditional asymmetric catalysis, chiral catalysts/additives are not required. Ample experiments combined with quantum chemical calculations established the origins of the stereogenic center and catalyst performance. The chirality at C4 in D-xylose was proved to be retained and successfully delivered to C2 in D-glyceric acid during C-C cleavage. The remarkable cooperative-roles of Ag+ and Ag0 in the constructed Ag/γ-Al2O3 catalyst are disclosed as the crucial contributors. Ag+ was responsible for low-temperature activation of D-xylose, while Ag0 facilitated the generation of active O* from O2. Ag+ and active O* cooperatively promoted the precise cleavage of the C2-C3 bond, and more importantly O* allowed the immediate fast oxidization of the D-glyceraldehyde intermediate to stabilize D-glyceric acid, thereby inhibiting the side reaction that induced racemization. This strategy makes a significant breakthrough in overcoming the limitation of poor enantioselectivity in current chemocatalytic conversion of biomass.

Neo-peripheral adaptive immune score predicts neoadjuvant chemotherapy for locally advanced breast cancer.

PURPOSE: Whether peripheral immune cell subsets can predict pathological complete response (pCR) in breast cancer patients remains to be elucidated. We aimed to dissect the relationship between peripheral immune cell subsets and pCR. METHODS: Two hundred and twenty-six eligible patients from two prospective clinical trials (SHPD001 and SHPD002) in China were randomly divided into a training cohort and a validation cohort. The breast cancer subtypes in this study included hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 95), HER2-positive (n = 100), and triple negative (n = 31) breast cancer. We defined the "Neo-Peripheral Adaptive Immune Score" for neoadjuvant chemotherapy (neoPAI Score) based on the percentages of CD4 + T cells, CD8 + T cells, B cells, and the CD4 + /CD8 + ratio in peripheral blood. We also evaluated the ability of the neoPAI Score derived from tumor-infiltrating immune cells (TIICs) to predict survival by employing The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database. RESULTS: In the training cohort, multivariate analysis showed that HR status [odds ratio (OR) 0.325; 95% confidence interval (CI) 0.135-0.761; P = 0.010], HER2 status (OR 2.657; 95% CI 1.266-5.730; P = 0.011), Ki67 index (OR 3.191; 95% CI 1.509-6.956; P = 0.003), histological grade (OR 2.297; 95% CI 1.031-5.290; P = 0.045) and neoPAI Score (OR 4.451; 95% CI 1.608-13.068; P = 0.005) were independent predictors of pCR. In the validation cohort, histological grade (OR 3.779; 95% CI 3.793-1.136 × 103; P = 0.008) and neoPAI Score (OR 90.828; 95% CI 3.827-9.843 × 103; P = 0.019) were independent predictors of pCR. The Immune Model that integrated the neoPAI Score was more accurate in predicting pCR than the Clinical Model that exclusively contained clinicopathological parameters in both cohorts. In TCGA-BRCA database, the neoPAI Score constructed from TIICs can predict the progression-free interval (P = 0.048) of breast cancer. CONCLUSION: The neoPAI Score defined by the percentages of peripheral immune cell subsets could be used as a potential biomarker for neoadjuvant chemotherapy efficacy.

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial.

BACKGROUND: There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations. METHODS: In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored. RESULTS: Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2-60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2-30.0), with median PFS of 5.6 months (95% CI, 2.8-8.4), and median OS of 10.5 months (95% CI, 8.7-12.3). The median duration of response was 9.9 months (95% CI, 6.2-13.6). All treatment-related adverse events (TRAEs) were grade 1-3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression. CONCLUSIONS: Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1800020262.

Silencing oncogene cell division cycle associated 5 induces apoptosis and G1 phase arrest of non-small cell lung cancer cells via p53-p21 signaling pathway.

BACKGROUNDS: As a regulator of cell cycle, cell division cycle-associated 5 (CDCA5) is involved in the progression of various malignant tumors. However, the potential relationship between CDCA5 and lung cancer has not been reported. METHODS: In our study, we analyzed the expression of CDCA5 in a variety of malignant tumors, performed Kaplan-Meier survival analysis of lung adenocarcinoma (LUAD), explored the potential relationship between CDCA5 expression and clinicopathological characteristics, assessed the predictive capability of at different stages of clinicopathological characteristics, revealed the enriched functions and signaling pathways among LUAD paitents with high CDCA5 expression, and investigated the correlation between PD-1, PD-L1, and CDCA5 through bioinformatics analyses. Subsequently, we performed quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) to demonstrate that CDCA5 mediates the p53-p21 pathway and regulates the cell cycle. RESULT: CDCA5 is probably involved in the occurrence and development of NSCLC, and function as a reliable biomarker for predicting the survival outcomes of patients with early stage of patients with LUAD. Furthermore, CDCA5 may be a promising indicator of immunotherapy efficacy. In addition, silencing the expression of CDCA5 significantly increased the proportion of apoptotic NSCLC cells, and caused NSCLC cells to be arrested in the G1 phase. CONSLUSION: In conclusion, CDCA5 regulated the cell cycle of NSCLC cells by mediating the p53-p21 signaling pathway, participating in the development and progression of NSCLC patients.

Ultrasound-Guided Breast Biopsy: Improved Accuracy of 10-G Cable-Free Elite Compared With 14-G CCNB.

BACKGROUND: Imaging-guided breast biopsy is crucial for breast lesion evaluation. We aim to make the first comprehensive comparison of two different ultrasound-guided breast biopsy devices: 14-G conventional core needle biopsy (CCNB) and the newly applied cable-free, low-vacuum-assisted 10-G breast biopsy system, Elite. METHODS: We retrospectively collected patients with suspected breast cancer who underwent ultrasound-guided 14-G CCNB or 10-G Elite from October 2013 through March 2018 and compared the biopsy result with the result after operation. We analyzed the test performance of the two methods and their accuracy in immunohistochemistry assays mainly including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki67. We also analyzed the accuracy of 10-G Elite with frozen sections. RESULTS: Six hundred seventy-four patients who underwent 14-G CCNB and 592 patients who underwent 10-G Elite were finally included in the research. Negative predictive value with Elite was higher than with CCNB (Elite 86.5%, CCNB 41.7%, P < 0.001). Sensitivity (Elite 97.7%, CCNB 96.2%, P = 0.1), specificity (Elite 98.7%, CCNB 90.0%, P = 0.1), positive predictive value (Elite 99.8%, CCNB 99.7%, P = 0.7), and false negative rate (Elite 2.3%, CCNB 3.8%, P = 0.1) showed no difference between two devices. In terms of immunohistochemistry assay, Ki67 agreement of Elite was higher than that of CCNB (Elite 79.5%, CCNB 73.4%, P = 0.045). Estrogen receptor agreement (Elite 90.6%, CCNB 87.7%, P = 0.2), progesterone receptor agreement (Elite 83.9%, CCNB 80.9%, P = 0.3), and human epidermal growth factor receptor two agreement (Elite 94.2%, CCNB 93.5%, P = 0.7) showed no difference between Elite and CCNB. The rate of an inconclusive biopsy result was lower with Elite than with CCNB (Elite 1.5%, CCNB 3.3%, P = 0.045). CONCLUSIONS: 10-G Elite has higher negative predictive value, higher Ki67 agreement, and lower inconclusive results than 14-G CCNB. Elite can be a reliable substitute for 14-G CCNB.

Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy.

BACKGROUND: Zinc finger E-box binding homeobox 1 (ZEB1) is a molecule involved in the progression of epithelial-to-mesenchymal transition (EMT) in various kinds of cancers. Here, we aimed to determine whether the expression of the ZEB1 protein is related to the response of patients to neoadjuvant therapy as well as their survival outcome. METHODS: Immunohistochemistry (IHC) was performed on paraffin-embedded tumor samples from core needle biopsy before neoadjuvant therapy (NAT). Univariate and multivariate logistic regression analyses were used to analyze the associations between the protein expression of ZEB1 and the pathological complete response (pCR) outcome. Kaplan-Meier plots and log-rank tests were used to compare disease-free survival (DFS) between groups. A Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidential interval (95% CI). RESULTS: A total of 75 patients were included in the IHC test. High ZEB1 protein expression was associated with a low pCR rate in both univariate (OR = 0.260, 95% CI 0.082-0.829, p = 0.023) and multivariate (OR = 0.074, 95% CI 0.011-0.475, p = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (p = 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024-79.519, p = 0.048). In hormone receptor positive (HorR-positive) patients, high ZEB1 protein expression was also associated with a lower pCR (OR = 0.054, 95% CI 0.007-0.422, p = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171-94.435, p = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (p = 0.042). CONCLUSIONS: Our results showed that high ZEB1 protein expression was a negative predictive marker of pCR and DFS in neoadjuvant therapy in breast cancer patients and in HorR-positive and HER2-overexpressing subgroups.Trial registration NCT, NCT02199418. Registered 24 July 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02199418?term=NCT02199418&rank=1. NCT, NCT 02221999. Registered 21 August 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02221999?term=NCT02221999&rank=1.

ROS1-ADGRG6: a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib.

BACKGROUND: ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1-2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes. CASE PRESENTATION: A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1-33 of ROS1 on chr6: q22.1 to exons of 2-26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib. CONCLUSION: We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.

Association of LncRNA MEG3 polymorphisms with efficacy of neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women, and neoadjuvant chemotherapy has been recommended to the patients with locally advanced breast cancer as the initial treatments. Long non-coding RNA (lncRNA) MEG3, an identified tumor suppressor, has been implicated in the development of various cancers. However, there is no data to evaluate the effect of MEG3 polymorphisms on neoadjuvant treatment in the breast cancer. METHODS: Genotyping was performed using Nanodispenser Spectro CHIP chip spotting and Mass ARRAY Compact System. Univariate and multivariate logistic regression analyses were used to analyze the associations between the MEG3 polymorphisms and the pathological complete response (pCR). The disease-free survival (DFS) was estimated by the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to calculate the hazard ratios (HRs) with a 95% confidential interval (CI). RESULTS: A total of 144 patients with available pretreatment blood species were enrolled in the SHPD002 clinic trial of neoadjuvant chemotherapy for breast cancer. MEG3 rs10132552 were significantly associated with good response (Adjusted OR = 2.79, 95% CI 1.096-7.103, p = 0.031) in dominant model. Median follow-up time was 20 months. In multiple regression analysis, rs10132552 TC + CC (adjusted HR = 0.127, 95% CI 0.22-0.728, p = 0.02) and rs941576 AG + GG (adjusted HR = 0.183, 95% CI 0.041-0.807, p = 0.025) were significantly associated with good DFS. MEG3 rs7158663 (OR = 0.377, 95% CI 0.155-0.917, p = 0.032) were associated with a low risk of hemoglobin decrease in dominant models. CONCLUSIONS: LncRNA MEG3 polymorphisms were associated with the chemotherapy response and toxicity of paclitaxel and cisplatin. The result indicates that MEG3 polymorphisms can be considered as the predictive and prognostic markers for the breast cancer patients. TRIAL REGISTRATION: Retrospectively registered (ClinicalTrials. Gov identifier: NCT02221999 ); date of registration: Aug 20th, 2014.

Consultation and treatment behaviour of infertile couples in China: a population-based study.

RESEARCH QUESTION: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China? DESIGN: Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy. RESULTS: Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy. CONCLUSION: The prevalence of infertility in China is high, but the uptake of treatment is relatively low.

Establishing a reentry procedure for human immunodeficiency virus screening-reactive donors in China.

BACKGROUND: Screening of blood donors for antibody to human immunodeficiency virus Types 1 and 2 (anti-HIV-1/2) and/or HIV nucleic acid test (NAT) is a well-established venue to prevent HIV transfusion-transmitted disease. However, with the current available technologies, HIV testing may result in donor loss due to false-positive results. This study intended to establish a donor reentry procedure for HIV screening-reactive donors in China. STUDY DESIGN AND METHODS: From September 1, 2013, to August 31, 2014, a total of 465 donors from 14 Chinese blood centers were enrolled in this study. Enrollment criteria include all donors who were screened reactive or belonged to the "gray zone" by enzyme-linked immunosorbent assay and/or reactive by NAT when tested at the local blood centers. All donor samples were sent to a central HIV confirmation laboratory where anti-HIV-1/2 and HIV individual-donation NATs were conducted. If the results were reactive for anti-HIV-1/2, then the samples were tested with a recombinant immunoblot assay. RESULTS: Based on the repeat testing at the central HIV confirmation laboratory 8 or 16 weeks after the study, 252 donors of 465 (54.2%) who completed the study could be classified in two categories for HIV status: 45 (18%) true positive and 207 (82%) false positive. A total of 213 of 465 (45.8%) donors were lost on follow-up and, thus, their HIV status cannot be determined with certainty. Based on these data, a donor reentry procedure was proposed. CONCLUSION: Based on our proposed donor reentry procedure for HIV screening-reactive donors, a majority of screening-positive donors (82%, 207/252) can be reentered safely.

Construction and validation of a prognostic signature based on anoikis-related lncRNAs in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is characterized by a high death rate and a poor prospect for survival. Anoikis, which is a kind of programmed cell apoptosis, is an important factor in the advancement of tumors. Nonetheless, the function of anoikis-related lncRNAs (ARLRs) in LUAD is still not well understood. The TCGA database was queried for genomic and clinical information. A prognostic signature for ARLRs was established via the use of coexpression analysis and Cox regression. Validation of the model's accuracy was conducted utilizing K-M curves and receiver operating characteristic (ROC) curves, and the signature was utilized to develop a nomogram. LncRNAs were implicated in the progression of tumors, as determined by functional enrichment analysis. There was an improvement in prognosis, increased immune cell infiltration, and higher immune scores among the low-risk patients. Additionally, we found that the two groups had varied anticancer drug sensitivities, which could help guide treatment. The impact of one ARLR, AC026355.2, on migration and invasion was validated by in vitro experiments in LUAD cells. Herein, a new lncRNA signature associated with anoikis was identified and estimated, potentially serving as a prognostic indicator for LUAD patients.

Serum lipid ratios as novel prognostic biomarkers for patients with locally advanced breast cancer treated with neoadjuvant therapy.

OBJECTIVES: To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. METHOD: This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated. RESULTS: Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708). CONCLUSION: Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation. CLINICAL TRIAL REGISTRATION: NCT05621564.

Lysosome-related genes: A new prognostic marker for lung adenocarcinoma.

Currently, a reliable early prognostic marker has not been identified for lung adenocarcinoma (LUAD), the most common malignancy. Recent studies demonstrated that lysosomal rupture is involved in cancer migration, progression, and immune microenvironment formation. We performed a bioinformatics analysis of lysosomal rupture to investigate whether lysosome-related genes (LRGs) are key in LUAD. The analysis identified 23 LRGs. Cytoscape visualization identified 10 core genes (CCNA2, DLGAP5, BUB1B, KIF2C, PBK, CDC20, NCAPG, ASPM, KIF4A, ANLN). With the 23 LRGs, we established a new risk scoring rule to classify patients with LUAD into high- and low-risk groups and verified the accuracy of the risk score by receiver operating characteristic curves and established a nomogram to evaluate clinical patients. Immunotherapy effectiveness between the high- and low-risk groups was evaluated based on the tumor mutational burden and analyses of immune cell infiltration and drug sensitivity. Pathway enrichment analysis revealed that lysosomes were closely associated with glucose metabolism, amino acid metabolism, and the immune response in patients with LUAD. Lysosomes are a likely new therapeutic target and provide new directions and ideas for treating and managing patients with LUAD.

Genetic polymorphisms of GGT1 gene (rs8135987, rs5751901 and rs2017869) are associated with neoadjuvant chemotherapy efficacy and toxicities in breast cancer patients.

BACKGROUND: Our previous study illustrated the predictive value of serum gamma-glutamyl transpeptidase (GGT) for neoadjuvant chemotherapy (NAC) sensitivity in breast cancer patients. In this study we aim to determine whether single nucleotide polymorphisms (SNPs) in the gamma-glutamyltransferase 1 (GGT1) gene are related to the NAC response and adverse events and to find out a genetic marker in predicting NAC sensitivity. METHODS: Three SNP loci (rs8135987, rs5751901, rs2017869) of GGT1 gene were selected and tested among breast cancer patients reciving NAC. Four genotype models were used in SNP analysis: co-dominant model compared AA vs. Aa vs. aa; dominant model compared AA vs. Aa + aa; recessive model compared AA + Aa vs. aa; over-dominant model compared AA + aa vs. Aa. Chi-squared test and multivariable logistic regression analysis were performed between SNP genotypes, haplotypes and pathological complete response(pCR), adverse events as well as serum GGT level. RESULTS: A total of 143 patients were included in the study. For SNP rs8135987 (T > C), the TC genotype in over-dominant model was inversely related with pCR (adjusted OR = 0.30, 95% CI 0.10-0.88, p = 0.029) as well as the risk of peripheral neuropathy (adjusted OR = 0.39, 95% CI 0.15-0.96, p = 0.042). The TC genotype in dominant model was significantly associated with elevated serum GGT level (OR = 3.11, 95% CI 1.07-9.02, p = 0.036). For rs2017869 (G > C), the occurrence of grade 2 or greater neutropenia (OR = 0.39, 95% CI 0.08-0.84, p = 0.025) and leukopenia (OR = 0.24, 95% CI 0.08-0.78, p = 0.017) were both significantly reduced in patients with CC genotypes. For rs5751901(T > C), the CC genotype could significantly reduce the risk of grade 2 or greater neutropenia (OR = 0.29, 95% CI 0.09-0.96, p = 0.036) and leukopenia (OR = 0.27, 95% CI 0.09-0.84, p = 0.024) in recessive model. CONCLUSIONS: The GGT1 gene SNPs might be an independent risk factor for poor response of NAC in breast cancer patients, providng theoretical basis for further precision therapy.

IKZF3 is a novel prognostic biomarker for head and neck squamous cell carcinoma: A study based on bioinformatics analysis.

In the past few years, immunotherapy of tumors has become an extensive research hotspot, and the value of IKZF family genes in the tumor microenvironment has also been increasingly recognized. However, the expression of the IKAROS family zinc finger 3 (IKZF3) gene in human head and neck squamous cell carcinoma (HNSCC) and its prognostic value were not reported for the main subset until now. In the present study, we analyzed the relationship between IKZF3 gene expression and the survival of HNSCC patients. To evaluate the potential of IKZF3 as a prognostic biomarker for HNSCC comprehensively, multiple online analysis tools, including UALCAN, cBioPortal, GEPIA, WebGestalt, String, Genomic Data Commons, and TIMER databases were utilized in our study. We observed that the HNSCC patients with higher IKZF3 expression tended to exhibit longer overall survival. Univariate and multivariate Cox regression analyses indicated that age and grade were independent prognostic indicators in HNSCC. Moreover, Gene Ontology and KEGG function enrichment analyses showed that several pathways in HNSCC might be pivotal pathways regulated by IKZF3, which revealed that IKZF3 was probably participating in the occurrence and development of HNSCC. Furthermore, the hypomethylation of the IKZF3 gene was closely associated with genes that observed mutation in HNSCC. IKZF3 was significantly correlated with several immune cells in HNSCC (e.g., CD8+ T cell, CD4+ cell, and dendritic cell). We explored the potential prognostic values and roles of the IKZF3 in HNSCC, revealing that IKZF3 was probably a novel and reliable prognostic biomarker for patients with HNSCC.

Precise diagnosis of breast phyllodes tumors using Raman spectroscopy: Biochemical fingerprint, tumor metabolism and possible mechanism.

BACKGROUND: Breast fibroadenomas and phyllodes tumors are both fibroepithelial tumors with comparable histological characteristics. However, rapid and precise differential diagnosis is a tough point in clinical pathology. Given the tendency of phyllodes tumors to recur, the difficulty in differential diagnosis with fibroadenomas leads to the difficulty in optimal management for these patients. METHOD: In this study, we used Raman spectroscopy to differentiate phyllodes tumors from breast fibroadenomas based on the biochemical and metabolic composition and develop a classification model. The model was validated by 5-fold cross-validation in the training set and tested in an independent test set. The potential metabolic differences between the two types of tumors observed in Raman spectroscopy were confirmed by targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 204 patients with formalin-fixed paraffin-embedded (FFPE) tissue samples, including 100 fibroadenomas and 104 phyllodes tumors were recruited from April 2014 to August 2021. All patients were randomly divided into the training cohort (n = 153) and the test cohort (n = 51). The Raman classification model could differentiate phyllodes tumor versus fibroadenoma with cross-validation accuracy, sensitivity, precision, and area under curve (AUC) of 85.58 % ± 1.77 %, 83.82 % ± 1.01 %, 87.65 % ± 4.22 %, and 93.18 % ± 1.98 %, respectively. When tested in the independent test set, it performed well with the test accuracy, sensitivity, specificity, and AUC of 83.50 %, 86.54 %, 80.39 %, and 90.71 %. Furthermore, the AUC was significantly higher for the Raman model than that for ultrasound (P = 0.0017) and frozen section diagnosis (P < 0.0001). When it came to much more difficult diagnosis between fibroadenoma and benign or small-size phyllodes tumor for pathological examination, the Raman model was capable of differentiating with AUC up to 97.45 % and 95.61 %, respectively. On the other hand, targeted metabolomic analysis, based on fresh-frozen tissue samples, confirmed the differential metabolites (including thymine, dihydrothymine, trans-4-hydroxy-l-proline, etc.) identified from Raman spectra between phyllodes tumor and fibroadenoma. SIGNIFICANCE AND NOVELTY: In this study, we obtained the molecular information map of breast phyllodes tumors provided by Raman spectroscopy for the first time. We identified a novel Raman fingerprint signature with the potential to precisely characterize and distinguish phyllodes tumors from fibroadenoma as a quick and accurate diagnostic tool. Raman spectroscopy is expected to further guide the precise diagnosis and optimal treatment of breast fibroepithelial tumors in the future.

Electron donation of Fe-Mn biochar for chromium(VI) immobilization: Key roles of embedded zero-valent iron clusters within iron-manganese oxide.

The dense surface passivation layer on zero-valent iron (ZVI) restricts its efficiency for water decontamination, causing a poor economy and waste of resources. Herein, we found that the ZVI on Fe-Mn biochar could afford a high electron-donating efficiency for the Cr(VI) reduction and immobilization. Over 78.0% of Fe in the Fe-Mn biochar was used for the Cr(VI) reduction and immobilization, i.e., 56.2 - 161.7 times higher than the commercial ZVI (0.5%) and modified ZVI (0.9 -1.3%), indicating that the unique ZVI species in Fe-Mn biochar offered an outstanding Fe utilization efficiency. We proposed that oxygen atoms in the FeO in the FeMnO2 precursor were removed during pyrolysis with biochar while the MnO skeleton was preserved, forming the embedded ZVI clusters within Fe-Mn oxide. The unique structure inhibited the formation of the Fe-Cr complex on Fe(0), which would facilitate the electron transfer between core Fe(0) and Cr(VI). Moreover, the surface FeMnO2 inhibited the diffusion of Fe and facilitated its affinity with pollutants, thus supporting higher efficiency for pollutant immobilization. The preserved performance of Fe-Mn biochar was proved in industrial wastewater and after long-term oxidation process, and the economic benefit was evaluated. This work provides a new approach for developing active ZVI-based materials with high Fe utilization efficiency and economics for water pollution control.

The inhibition of p-hydroxyphenyl hydroxyl group in residual lignin on enzymatic hydrolysis of cellulose and its underlying mechanism.

The controlling factors of the inhibition on enzymatic hydrolysis caused by residual lignin were identified with molecular level understanding of the mechanism. Residual lignin samples with different properties were isolated, characterized and added into the enzymatic hydrolysis of Avicel. It was found that the phenolic hydroxyl group (OH) was the main inhibitor in residual lignin, and the p-hydroxyphenyl OH was the crucial sub-structure that exhibited the highest inhibition and non-productive adsorption, ascribing to its higher electrophilicity and lower steric hindrance. The H-bond interaction and π-π stacking between phenolic OH of lignin and phenolic OH of tyrosine on the planar face of carbohydrate binding module of cellulase were probably responsible for the non-productive adsorption. The binding sites of H-bonds may be the H in phenolic OH of lignin and the O in phenolic OH of tyrosine, respectively, and that of the π-π stacking may be the benzene rings of them.

Detection of NDM-1-Positive Aeromonas caviae from Bacteremia by Using Whole-Genome Sequencing.

Purpose: Nosocomial infections caused by New Delhi metallo-ß-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients. Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene bla NDM-1 and also have antibiotic resistance genes such as ß-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship. Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded bla NDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.