High-density genetic map construction and QTL mapping of a zigzag-shaped stem trait in tea plant (Camellia sinensis).

The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.

A key mutation in magnesium chelatase I subunit leads to a chlorophyll-deficient mutant of tea (Camellia sinensis).

Tea (Camellia sinensis) is a highly important beverage crop renowned for its unique flavour and health benefits. Chlorotic mutants of tea, known worldwide for their umami taste and economic value, have gained global popularity. However, the genetic basis of this chlorosis trait remains unclear. In this study, we identified a major-effect quantitative trait locus (QTL), qChl-3, responsible for the chlorosis trait in tea leaves, linked to a non-synonymous polymorphism (G1199A) in the magnesium chelatase I subunit (CsCHLI). Homozygous CsCHLIA plants exhibited an albino phenotype due to defects in magnesium protoporphyrin IX and chlorophylls in the leaves. Biochemical assays revealed that CsCHLI mutations did not affect subcellular localization or interactions with CsCHLIG and CsCHLD. However, combining CsCHLIA with CsCHLIG significantly reduced ATPase activity. RNA-seq analysis tentatively indicated that CsCHLI inhibited photosynthesis and enhanced photoinhibition, which in turn promoted protein degradation and increased the amino acid levels in chlorotic leaves. RT-qPCR and enzyme activity assays confirmed the crucial role of asparagine synthetase and arginase in asparagine and arginine accumulation, with levels increasing over 90-fold in chlorotic leaves. Therefore, this study provides insights into the genetic mechanism underlying tea chlorosis and the relationship between chlorophyll biosynthesis and amino acid metabolism.

Assessment of cognitive dysfunction and its influencing factors after acute ischemic stroke.

OBJECTIVE: In order to provide a more accurate and effective basis for clinical diagnosis and treatment, patients with cognitive dysfunction after acute ischemic stroke (AIS) were evaluated and their influencing factors were analyzed. METHODS: A rigorous and systematic logistic regression analysis was conducted to comprehensively investigate the various influencing factors that contribute to cognitive dysfunction. RESULTS: Among them, the sex granulocyte/lymphocyte ratio (NLR), low-density lipoprotein cholesterol (LDL-C) level, and C-reactive protein (CRP) were also higher than those in the control group (p < 0.05). The scores of memory, orientation, visual and spatial function, abstract thinking and language in the control group were higher than those in the experimental group (p < 0.05). The results of multivariate logistic regression analysis showed that history of diabetes mellitus, high NLR, high LDL-C, high CRP, smoking and temporal lobe infarction were risk factors for cognitive dysfunction after AIS, while elevated BMI and love of exercise were protective factors for cognitive dysfunction after AIS. CONCLUSION: Patients with cognitive dysfunction had the highest incidence of temporal lobe infarction, and they scored lower than the control group on memory, orientation, visual and spatial function, abstract thinking, and language function. Multivariate logistic regression analysis showed that a history of diabetes mellitus, high NLR, high LDL-C, high CRP, smoking, and temporal lobe infarction were independent risk factors for cognitive dysfunction after acute ischemic stroke, while elevated BMI and a love of exercise were protective factors for cognitive dysfunction after acute ischemic stroke.

Bulked Segregant RNA-Seq Reveals Different Gene Expression Patterns and Mutant Genes Associated with the Zigzag Pattern of Tea Plants (Camellia sinensis).

The unique zigzag-patterned tea plant is a rare germplasm resource. However, the molecular mechanism behind the formation of zigzag stems remains unclear. To address this, a BC1 genetic population of tea plants with zigzag stems was studied using histological observation and bulked segregant RNA-seq. The analysis revealed 1494 differentially expressed genes (DEGs) between the upright and zigzag stem groups. These DEGs may regulate the transduction and biosynthesis of plant hormones, and the effects on the phenylpropane biosynthesis pathways may cause the accumulation of lignin. Tissue sections further supported this finding, showing differences in cell wall thickness between upright and curved stems, potentially due to lignin accumulation. Additionally, 262 single-nucleotide polymorphisms (SNPs) across 38 genes were identified as key SNPs, and 5 genes related to zigzag stems were identified through homologous gene function annotation. Mutations in these genes may impact auxin distribution and content, resulting in the asymmetric development of vascular bundles in curved stems. In summary, we identified the key genes associated with the tortuous phenotype by using BSR-seq on a BC1 population to minimize genetic background noise.

Effect of sequential versus single-step culture medium on IVF treatments, including embryo and clinical outcomes: a prospective randomized study.

PURPOSE: Sequential media G5 series (Vitrolife) and single-step medium Continuous Single Culture Complete (CSC-C) (Irvine Scientific) are two different culture media. We want to examine difference between culturing effects of the two media. METHODS: To compare the fertilization and early embryo development, a prospective randomized controlled trial with sibling oocytes in infertile patients, aged ≤ 45 years with ≥ 8 oocytes (226 cycles) was conducted. Each half of the retrieved oocytes from the same patient were randomly allocated to two culture media separately. The remaining fresh cycles were randomly assigned to two culture media during the same period (179 cycles). We compared the clinical outcomes based on the total fresh ET cycles in this periods, in which the transferred embryos were only from one culture medium. RESULTS: Embryo outcomes: 226 cycles, included 176 IVF and 50 ICSI cycles, were analyzed, which correspond to 3518 inseminated or micro-injected oocytes. CLINICAL OUTCOMES: 71 (CSC-C) and 71 (G5 series) fresh ET cycles were compared. There were no significant differences in clinical outcomes and general fertilization rate. However, the fertilization rate was superior in the CSC-C when compared with G5 in ICSI cycles (76.51% vs. 67.25%, P = 0.008). In addition, the compacted embryo development rate was significantly higher in CSC-C on day 3. The cycles that had compacted embryos on day 3 demonstrated better outcomes both in embryos as well as clinically. CONCLUSIONS: CSC-C had higher fertilization rates than G5 series in ICSI cycles. In addition, the compaction rates of day 3 embryos were significantly higher in CSC-C.

Precise theoretical model for quantum-dot color conversion.

Quantum-dot color conversion (QDCC) is a promising technique for next-generation full-color displays, such as QD converted organic light-emitting diodes and micro light-emitting diodes. Although present QDCC research has made some progress on the experimental aspect, the optical model and corresponding mathematical expression that can lay an indispensable foundation for QDCC have not been reported yet. In this paper, we present a theoretical model for precisely describing the complete optical behavior of QDCC, including optical transmission, scattering, absorption, and conversion process. A key parameter of QDCC, called dosage factor (DoF), is defined to quantitatively express the total consumption of QDs that can be calculated as the product of film thickness and QD concentration. Theoretical relations are established between DoF and three key performance indicators of QDCC, namely the light conversion efficiency (LCE), blue light transmittance (BLT), and optical density (OD). The maximum LCE value can be predicted based on this theoretical model, as well as the relationship between the slope of the OD curve and the molar absorption coefficient of blue light. This theoretical model is verified by both simulation and experiment. Results show that the simulation and experimental data highly match the theoretical model, and the goodness of fit reaches higher than 96% for LCE, BLT, and OD. Based on this, the optimal interval of DoF is recommended that provides key guiding significance to the QDCC related experiment.

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA-328-3p-mediated inhibition of COL1A1.

Circular RNAs (circRNAs) are a group of non-coding RNAs implicated in the pathogenesis of cancer progression, which exert their functions via regulation of microRNAs (miRNAs) and genes. The present study uses gain- and loss-of-function approaches to evaluate the functions of hsa_circRNA_002178 in angiogenesis along with energy metabolism and underlying downstream signals. The expression pattern of hsa_circRNA_002178 in clinical breast cancer tissues and its association with prognosis were characterized at first. Next, the energy metabolism and angiogenesis as well as cell viability were evaluated when the expression of hsa_circRNA_002178 in breast cancer cells was knocked down by siRNA. The interaction between hsa_circRNA_002178 and its downstream miR-328-3p was identified, followed by the analysis of their functions in regulation of breast cancer cellular behaviours. The target gene of miR-328-3p was predicted and verified, followed by identifying its role in the breast cancer progression. Higher expression of hsa_circRNA_002178 shared an association with worse prognosis in breast cancer. The inhibition of hsa_circRNA_002178 resulted in reductions in cell viability, energy metabolism and tube formation ability. Hsa_circRNA_002178 could competitively bind to miR-328-3p and down-regulated its expression. Restoration of miR-328-3p eliminated the tumour-promoting effects of hsa_circRNA_002178. COL1A1, as a target of miR-328-3p, could be up-regulated by overexpression of hsa_circRNA_002178. In vivo experiments further confirmed the inhibition of tumour growth and inflammation by silencing hsa_circRNA_002178 or up-regulating miR-328-3p. Taken together, hsa_circRNA_002178 is highlighted as a promising target for breast cancer due to the anti-tumour effects achieved by silencing hsa_circRNA_002178.

Genetic analysis of embryo in a human case of spontaneous oocyte activation: a case report.

Parthenogenesis, a unique form of reproduction, is normally inhibited in mammals and a human embryo with parthenogenetic origin is not considered capable of producing offspring. The aim of this report is to analyze a parthenogenetic oocyte retrieved from a patient so as to have a better understanding on parthenogenesis and causes of infertility. A 38-year-old woman presented at our center with a history of primary infertility for 10 years and underwent an IVF-ICSI cycle. Three MII oocytes retrieved and one of which presented with 1 pronucleus before conducting ICSI and developed into an embryo 30 h post-retrieval. Blastomere biopsy, genome amplification, copy number variation (CNV) analysis and MultiSNPs analysis was performed on the embryo. The results showed that only one blastomere contains DNA and CNV analysis indicated a genotype of 48, XX, +17, +17 and the genetic contribution of biopsied embryo was of exclusively maternal origin. Such analysis might be beneficial for patients with a history of oocyte spontaneous activation in diagnosing case-specific aberrations and providing individualized therapeutic strategies such as preimplantation genetic diagnosis to choose a genetic normal embryo to transplant.

Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis.

OBJECTIVES: Patients with gallbladder carcinoma (GBC) lack effective treatment methods largely due to the inadequacy of both molecular characterisation and potential therapeutic targets. We previously uncovered a spectrum of genomic alterations and identified recurrent mutations in the ErbB pathway in GBC. Here, we aimed to study recurrent mutations of genes and pathways in a larger cohort of patients with GBC and investigate the potential mechanisms and clinical significance of these mutations. DESIGN: We performed whole-exome sequencing (WES) in 157 patients with GBC. Functional experiments were applied in GBC cell lines to explore the oncogenic roles of ERBB2/ERBB3 hotspot mutations, their correlation with PD-L1 expression and the underlying mechanisms. ERBB inhibitors and a PD-L1 blocker were used to evaluate the anticancer activities in co-culture systems in vitro and in vivo. RESULTS: WES identified ERBB2 and ERBB3 mutations at a frequency of 7%-8% in the expanded cohort, and patients with ERBB2/ERBB3 mutations exhibited poorer prognoses. A set of in vitro and in vivo experiments revealed increased proliferation/migration on ERBB2/ERBB3 mutation. Ectopic expression of ERBB2/ERBB3 mutants upregulated PD-L1 expression in GBC cells, effectively suppressed normal T-cell-mediated cytotoxicity in vitro through activation of the PI3K/Akt signalling pathway and contributed to the growth and progression of GBC in vivo. Treatment with an ERBB2/ERBB3 inhibitor or a PD-L1 monoclonal antibody reversed these immunosuppressive effects, and combined therapy revealed promising therapeutic activities. CONCLUSIONS: ERBB2/ERBB3 mutations may serve as useful biomarkers in identifying patients who are sensitive to ERBB2/ERBB3 inhibitors and PD-L1 monoclonal antibody treatment. TRIAL REGISTRATION NUMBER: NCT02442414;Pre-results.

NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma.

NOP2/Sun domain family, member 2 (NSUN2) is a nuclear RNA methyl-transferase catalyzing 5-methylcytosine formation. Evidence shows that NSUN2 is correlated with cell unlimited proliferation. However, its functional role in gallbladder carcinoma (GBC), which is the most common biliary tract malignancy and has a poor prognosis, remains to be determined. Here we found that NSUN2 was highly expressed in GBC tissues as well as cell lines. NSUN2 silencing repressed GBC cell proliferation and tumorigenesis both in vitro and in vivo. Conversely, upregulation of NSUN2 enhanced GBC cell growth and colony formation. We further discovered that RPL6 was a closely interacting partner with NSUN2. Silencing RPL6 resulted in insufficient NSUN2 translational level and accumulative NSUN2 transcriptional level. Exogenous expression of NSUN2 partially rescued the effect of RPL6 in gallbladder cancer progression. Taken together, our data provided novel mechanic insights into the function of NSUN2 in GBC, thus pointing to NSUN2 as a potential and effective therapeutic approach to GBC treatment.

MicroRNA-1275 inhibits cell migration and invasion in gastric cancer by regulating vimentin and E-cadherin via JAZF1.

BACKGROUND: Emerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer. In this study, we analysed the role and mechanism of miR-1275 in the progression and prognosis of gastric cancer (GC). METHODS: Target genes of miR-1275 were identified and verified by luciferase assay and Western blotting. The function of miR-1275 in invasion and metastasis was analysed in vitro and in vivo in nude mice. The signal pathway regulated by miR-1275 was examined by qRT-PCR, Western blotting and chromatin immunoprecipitation analyses. The expression of miR-1275and JAZF1 were measured in specimens of GC and adjacent non cancerous tissues. RESULTS: We identified JAZF1 as a direct miR-1275 target. miR-1275 supresses migration and invasion of GC cells in vitro and in vivo, which was restored by JAZF1 overexpression. Moreover, JAZF1 was recognized as a direct regulator of Vimentin. Knocking-down miR-1275 or overexpressing JAZF1 resulted in upregulation of Vimentin but downregulation of E-cadherin. Meanwhile, we validated in 120 GC patients specimens that low miR-1275expression and high JAZF1 mRNA expression levels were closely associated with lymph node metastasis and poor prognosis. The expression of JAZF1 in protein level displayed the correlations with Vimentin but inversely with E-cadherin. CONCLUSIONS: Increased miR-1275 expression inhibited GC metastasis by regulating vimentin/E-cadherin via direct suppression of JAZF1expression, suggesting that miR-1275 is a tumour-suppressor miRNA with the potential as a prognostic biomarker or therapeutic target in GC.

National surveys on 15 quality indicators for the total testing process in clinical laboratories of China from 2015 to 2017.

Background As effective quality management tools, quality indicators (QIs) are widely used in laboratory medicine. This study aimed to analyze the results of QIs, identify errors and provide quality specifications (QSs) based on the state-of-the-art. Methods Clinical laboratories all over China participated in the QIs survey organized by the National Health Commission of People' Republic of China from 2015 to 2017. Most of these QIs were selected from a common model of QIs (MQI) established by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All participants were asked to submit general information and original QIs data through a medical quality control data collection system. The results of QIs were reported in percentages and sigma, except turnaround time (TAT) which was measured in minutes. The 25th, 50th and 75th percentiles were, respectively, calculated as three levels of QSs, which were defined starting from the model proposed during the 1st Strategic Conference of the EFLM on "Defining analytical performance 15 years after the Stockholm Conference on Quality Specification in Laboratory Medicine". Results A total of 76 clinical laboratories from 25 provinces in China continuously participated in this survey and submitted complete data for all QIs from 2015 to 2017. In general, the performance of all reported QIs have improved or at least kept stable over time. Defect percentages of blood culture contamination were the largest in the pre-analytical phase. Intra-laboratory TAT was always larger than pre-examination TAT. Percentage of tests covered by inter-laboratory comparison was relatively low than others in the intra-analytical phase. The performances of critical values notification and timely critical values notification were the best with 6.0σ. The median sigma level of incorrect laboratory reports varied from 5.5σ to 5.7σ. Conclusions QSs of QIs provide useful guidance for laboratories to improve testing quality. Laboratories should take continuous quality improvement measures in all phases of total testing process to ensure safe and effective tests.

Development of a Combined Human Transferrin-Hemoglobin Lateral Immunochromatographic Assay for Accurate and Rapid Fecal Occult Blood Test.

BACKGROUND: Fecal occult bloodtest (FOBT) plays an important role in the diagnosis of gastrointestinal diseases. The sensitivities of current FOBT methods are still not satisfactory. The aim of this study is to develop a combined human transferrin (HTf)-hemoglobin (HHb) lateral flow assay (LFA) for accurate and rapid FOBT. METHODS: Monoclonal antibodies (MAbs) targeting HTf were developed by conventional methods and paired using LFA strips. The best HTf MAb pair was chosen according to the overall performance on testing limit and specificity. Meanwhile, HHb LFA strips were prepared using previously developed HHb MAbs. The testing limit and specificity were characterized. Based on the selected HTf MAb pair and the verified HHb MAb pair, combined HTf-HHb strips were developed. The combined HTf-HHb strips were used for FOBT of 400 human fecal samples, including 200 gastrointestinal bleeding specimens and 200 healthy subjects. For comparison, the homemade individual HTf and HHb strips, as well as three kinds of commercial FOBT strips, were also used for the FOBT. RESULTS: Two MAb pairs targeting HTf were developed for LFA. Two types of HTf strips were prepared accordingly. The type I was chosen due to its lower detection limit. Using the type I HTf MAb pair and the verified HHb- MAb pair, the combined HTf-HHb strips could detect the HTf at concentrations between 1 ng/mL and 1 x 106 ng/mL and the HHb between 10 ng/mL and 2.5 x 106 ng/mL. Compared to individual HTf and HHb strips and three kinds of commercial strips, the combined strips showed the highest diagnostic sensitivity in FOBT (96.0%). The specificity was a satisfactory 99%. CONCLUSIONS: Our combined HTf-HHb test strips are a very promising product for accurate and rapid FOBT.

Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells.

Metformin is the most commonly used drug for type 2 diabetes and has potential benefit in treating and preventing cancer. Previous studies indicated that membrane proteins can affect the antineoplastic effects of metformin and may be crucial in the field of cancer research. However, the antineoplastic effects of metformin and its mechanism in gallbladder cancer (GBC) remain largely unknown. In this study, the effects of metformin on GBC cell proliferation and viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay and an apoptosis assay. Western blotting was performed to investigate related signaling pathways. Of note, inhibition, knockdown and upregulation of the membrane protein Chloride intracellular channel 1 (CLIC1) can affect GBC resistance in the presence of metformin. Our data demonstrated that metformin apparently inhibits the proliferation and viability of GBC cells. Metformin promoted cell apoptosis and increased the number of early apoptotic cells. We found that metformin can exert growth-suppressive effects on these cell lines via inhibition of p-Akt activity and the Bcl-2 family. Notably, either dysfunction or downregulation of CLIC1 can partially decrease the antineoplastic effects of metformin while upregulation of CLIC1 can increase drug sensitivity. Our findings provide experimental evidence for using metformin as an antitumor treatment for gallbladder carcinoma.

MYBL2 is a Potential Prognostic Marker that Promotes Cell Proliferation in Gallbladder Cancer.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC. METHODS: MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice. RESULTS: MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects. CONCLUSIONS: MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients.

Casticin induces apoptosis and G0/G1 cell cycle arrest in gallbladder cancer cells.

BACKGROUND: Casticin, the flavonoid extracted from Vitex rotundifolia L, exerts various biological effects, including anti-inflammatory and anti-cancer activity. The aim of this study is to investigate the effects and mechanisms of casticin in human gallbladder cancer cells. METHODS: Human NOZ and SGC996 cells were used to perform the experiments. CCK-8 assay and colony formation assay were performed to evaluate cell viability. Cell cycle analyses and annexin V/PI staining assay for apoptosis were measured using flow cytometry. Western blot analysis was used to evaluate the changes in protein expression, and the effect of casticin treatment in vivo was experimented with xenografted tumors. RESULTS: In this study, we found that casticin significantly inhibited gallbladder cancer cell proliferation in a dose- and time-dependent manner. Casticin also induced G0/G1 arrest and mitochondrial-related apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, casticin induced cycle arrest and apoptosis by upregulating p27 and downregulating cyclinD1/cyclin-dependent kinase4 and phosphorylated protein kinase B. In vivo, casticin inhibited tumor growth. CONCLUSION: Casticin induces G0/G1 arrest and apoptosis in gallbladder cancer, suggesting that casticin might represent a novel and effective agent against gallbladder cancer.

National Survey on Internal Quality Control Practice for Lipid Parameters in Laboratories of China from 2014 to 2016.

BACKGROUND: To investigate the situation of Internal Quality Control (IQC) practice for total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from 2014 to 2016 in laboratories in China and provide improvement measurements. METHODS: A web-based External Quality Assessment (EQA) system was used to collect IQC data of lipid parameters in laboratories which continuously participated in the national EQA programs in China from 2014 to 2016. Pass rate of the coefficients of variation (CVs) of two level quality controls in four lipid parameters were calculated according to six quality specifications for precision to evaluate the current status of precision level of the four lipid parameters and their change over time in China. RESULTS: 533, 512, 504, and 466 laboratories continuously reported the data of level one for total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol, and 212, 210, 208 and 198 laboratories reported the level two, respectively. The percentage of laboratories meeting the quality specification varied based on different criteria. Non-significant change can be found in the pass rate of CVs over time. The number of laboratories using a closed system increased over time, but still only accounted for a small proportion. There is no significant difference in the pass rate of CVs between closed and open systems. CONCLUSIONS: Triglycerides currently have a fairly good performance in China. While the performance of laboratories on total cholesterol, HDL-cholesterol and LDL-cholesterol has yet to be improved.

Knockdown of SALL4 inhibits the proliferation and reverses the resistance of MCF-7/ADR cells to doxorubicin hydrochloride.

BACKGROUND: Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer. RESULTS: Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo. CONCLUSION: SALL4 knockdown inhibits the growth of the drug resistant breast cancer due to cell cycle arrest and reverses tumor chemo-resistance through down-regulating the membrane transporter, BCPR. Thus, SALL4 has potential as a novel target for the treatment of breast cancer.

A Network Meta-analysis of Randomized Controlled Trials Focusing on Different Allergic Rhinitis Medications.

This study is aimed to investigate the effectiveness of 4 allergic rhinitis (AR) drugs (loratadine, cetirizine, montelukast, and desloratadine) in reducing functional problems in patients, as indicated by rhinoconjunctivitis quality of life questionnaire scores. After an exhaustive search of electronic databases containing published scientific literature, high-quality randomized controlled trials relevant to our study were selected based on a stringent predefined inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 and comprehensive meta-analysis (CMA 2.0) software. The literature search broadly identified 386 studies, and after a multistep screening and elimination process, a total of 13 randomized controlled trials contributed to this network meta-analysis. These 13 high-quality studies contained a combined total of 6867 patients with AR on 4 different medications. The results of network meta-analysis revealed that, compared with placebo, all 4 mediations treated AR effectively [cetirizine: mean: -0.62, 95% confidence intervals (95% CI) = -0.90 to -0.34, P < 0.001; loratadine: mean: -0.32, 95% CI = -0.55 to -0.097, P = 0.005; montelukast: mean: -0.28, 95% CI = -0.54 to -0.023, P = 0.033; desloratadine: mean: -0.39, 95% CI = -0.60 to -0.18, P < 0.001]. A comparison of surface under the cumulative ranking curve values of these 4 interventions clearly showed that cetirizine is the most optimal medication for AR treatment. In conclusion, this network meta-analysis provides the first evidence that cetirizine is the most efficacious treatment for AR compared with loratadine, montelukast, and desloratadine, significantly reducing the functional problems in patients with AR.

Correction: Xiang, S., et al. Schisandrin B Induces Apoptosis and Cell Cycle Arrest of Gallbladder Cancer Cells. Molecules 2014, 19, 13235-13250.

We would like to change the Affiliation addresses on Page 13235 of paper [1], [...].