Advances in mRNA vaccines for viral diseases.

Since the onset of the pandemic caused by severe acute respiratory syndrome coronavirus 2, messenger RNA (mRNA) vaccines have demonstrated outstanding performance. mRNA vaccines offer significant advantages over conventional vaccines in production speed and cost-effectiveness, making them an attractive option against other viral diseases. This article reviewed recent advances in viral mRNA vaccines and their delivery systems to provide references and guidance for developing mRNA vaccines for new viral diseases.

Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases. We provide an overview of the optimization of the mRNA vaccine development process as well as the good immune efficacy and safety shown in clinical studies. In addition, we also provide a brief description of the important role of mRNA immunomodulators in the treatment of viral diseases. After that, it will provide a good reference or strategy for research on mRNA vaccines used in clinical medicine with more stable structures, higher translation efficiency, better immune efficacy and safety, shorter production time, and lower production costs than conditional vaccines to be used as preventive or therapeutic strategy for the control of viral diseases in the future.

ADAMTS1 as potential prognostic biomarker promotes malignant invasion of glioma.

BACKGROUND: Glioma is the most common intracranial malignancy in adults with a high degree of malignancy and poor prognosis, which is largely attributed to the existence of glioma stem cells (GSCs). Previous evidence indicated that the matrix metalloproteinase ADAMTS1 was implicated in the process of tumor invasion, but the involvement of ADAMTS1 in glioma malignant invasion remains poorly understood. METHODS: The expression and prognosis values of ADAMTS1 were investigated in patients with glioma based on ONCOMINE and GEPIA databases. ADAMTS1 expression of different malignancy grade tissues was determined by immunohistochemistry. The effects of ADAMTS1 on cell proliferation and invasion were determined by clone formation assay and Transwell migration assay. The animal experiment was performed in an intracranial orthotopic xenograft model by knockout of ADAMTS1. Stemness properties and Notch1-SOX2 pathway were examined in stable ADAMTS1 knockdown GSCs. RESULTS: The expression levels of ADAMTS1 were significantly higher in glioma tissues and significantly correlated with the grade of malignancy and prognosis of glioma. Elevated ADAMTS1 expression was associated with SOX2, N-cadherin and the resistance of chemoradiotherapy of glioma patients. ADAMTS1 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Mechanistically, we found a blockade of the migration and invasiveness of GSCs and the expression levels of Notch1 and SOX2 in absence of ADAMTS1. CONCLUSION: As a biomarker for prediction of prognosis, ADAMTS1 may affect the invasive phenotype of GSCs by regulating Notch1-SOX2 signaling pathway, thereby promoting the invasive growth of glioma.

HBV Enhances Sorafenib Resistance in Hepatocellular Carcinoma by Reducing Ferroptosis via SRSF2-Mediated Abnormal PCLAF Splicing.

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. Hepatitis B virus (HBV) infection accounts for nearly 50% of HCC cases. Recent studies indicate that HBV infection induces resistance to sorafenib, the first-line systemic treatment for advanced HCC for more than a decade, from 2007 to 2020. Our previous research shows that variant 1 (tv1) of proliferating cell nuclear antigen clamp-associated factor (PCLAF), overexpressed in HCC, protects against doxorubicin-induced apoptosis. However, there are no reports on the relevance of PCLAF in sorafenib resistance in HBV-related HCC. In this article, we found that PCLAF levels were higher in HBV-related HCC than in non-virus-related HCC using bioinformatics analysis. Immunohistochemistry (IHC) staining of clinical samples and the splicing reporter minigene assay using HCC cells revealed that PCLAF tv1 was elevated by HBV. Furthermore, HBV promoted the splicing of PCLAF tv1 by downregulating serine/arginine-rich splicing factor 2 (SRSF2), which hindered the inclusion of PCLAF exon 3 through a putative cis-element (116-123), "GATTCCTG". The CCK-8 assay showed that HBV decreased cell susceptibility to sorafenib through SRSF2/PCLAF tv1. HBV reduced ferroptosis by decreasing intracellular Fe2+ levels and activating GPX4 expression via the SRSF2/PCLAF tv1 axis, according to a mechanism study. Suppressed ferroptosis, on the other hand, contributed to HBV-mediated sorafenib resistance through SRSF2/PCLAF tv1. These data suggested that HBV regulated PCLAF abnormal alternative splicing by suppressing SRSF2. HBV caused sorafenib resistance by reducing ferroptosis via the SRSF2/PCLAF tv1 axis. As a result, the SRSF2/PCLAF tv1 axis may be a prospective molecular therapeutic target in HBV-related HCC, as well as a predictor of sorafenib resistance. The inhibition of the SRSF2/PCLAF tv1 axis may be crucial in the emergence of systemic chemotherapy resistance in HBV-associated HCC.

A validated UPLC-MS/MS method for quantification of glutamine in plasma and pharmacokinetic study of oral glutamine tablets in healthy Beagles.

This study aimed to clarify the laws of glutamine tablets absorption, distribution, and metabolism in Beagles and to provide a basis for formulating dosing regimens. Twelve healthy Beagles were enrolled the absolute bioavailability study with a crossover design . Glutamine tablets (240 mg/kg b.w.) or glutamine sterile solution (60 mg/kg b.w.) were administered. A method for the determination of glutamine in Beagles' plasma by UPLC-MS/MS was established, with high sensitivity, specificity, and simplicity. Based on the study of endogenous glutamine concentration, the mean concentration of the four time points before drug administration was selected as the background concentration of glutamine. Pharmacokinetic parameters were calculated by non-compartment model. The Cmax of glutamine was 136.11 ± 72.51 µg/ml, Tmax was 0.85 ± 0.29 h, and t1/2λz was 0.42 ± 0.27 h after oral administration. The AUC0-t of glutamine was 116.30 ± 75.15 h·µg/ml vs. 44.55 ± 22.48 h·µg/ml following oral and IV administration, respectively, with an absolute bioavailability of 64.74% ± 19.18%. The results showed glutamine was quickly absorbed and eliminated in Beagles with high bioavailability. Therefore, glutamine is suitable to be prepared as oral tablets and recommended to shorten the dosing interval.

A systematic review of ozone therapy for treating chronically refractory wounds and ulcers.

This study aims at evaluating the efficacy and safety of ozone therapy for chronic wounds. The Cochrane Library, PubMed, Ovid Embase, Web of Science, and Chinese Biomedical Literature Database were searched. Randomised controlled trials (RCTs) about participants with chronic wounds were included. Risk of bias assessment was performed by the Cochrane risk-of-bias tool. A randomised-effects model was applied to pool results according to the types of wounds or ulcers. Among 12 included studies, ozone was implemented by topical application (ozone gas bath, ozonated oil, ozone water flushing) and systematic applications including autologous blood immunomodulation and rectal insufflation. The results indicated compared with standard control therapy for diabetic foot ulcers, ozone therapy regardless of monotherapy or combined control treatment markedly accelerated the improvement of the wound area(standardised mean difference(SMD) = 66.54%, 95% confidence interval (CI) = [46.18,86.90], P < .00001) and reduced the amputation rate (risk ration (RR) = 0.36, 95% CI = [0.24,0.54], P < .00001). But there is no improvement in the proportion of participants with completely healed wounds and length of hospital stay. No adverse events associated with ozone treatment have been reported. And the efficacy of ozone therapy for other wound types is still uncertain because of no sufficient studies. More high-quality randomised controlled trials are needed to confirm the efficacy and safety of ozone therapy for chronic wounds or ulcers.

TRAPPC13 Is a Novel Target of Mesorhizobium amorphae Type III Secretion System Effector NopP.

Similar to pathogenic bacteria, rhizobia can inject effector proteins into host cells directly to promote infection via the type III secretion system (T3SS). Nodulation outer protein P (NopP), a specific T3SS effector of rhizobia, plays different roles in the establishment of multiple rhizobia-legume symbiotic systems. Mesorhizobium amorphae CCNWGS0123 (GS0123), which infects Robinia pseudoacacia specifically, secretes several T3SS effectors, including NopP. Here, we demonstrate that NopP is secreted through T3SS-I of GS0123 during the early stages of infection, and its deficiency decreases nodule nitrogenase activity of R. pseudoacacia nodules. A trafficking protein particle complex subunit 13-like protein (TRAPPC13) has been identified as a NopP target protein in R. pseudoacacia roots by screening a yeast two-hybrid library. The physical interaction between NopP and TRAPPC13 is verified by bimolecular fluorescence complementation and coimmunoprecipitation assays. In addition, subcellular localization analysis reveals that both NopP and its target, TRAPPC13, are colocalized on the plasma membrane. Compared with GS0123-inoculated R. pseudoacacia roots, some genes associated with cell wall remodeling and plant innate immunity down-regulated in ΔnopP-inoculated roots at 36 h postinoculation. The results suggest that NopP in M. amorphae CCNWGS0123 acts in multiple processes in R. pseudoacacia during the early stages of infection, and TRAPPC13 could participate in the process as a NopP target.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer.

BACKGROUND: Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic. METHODS: Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential. RESULTS: Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. CONCLUSIONS: The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC.

Safety and Efficacy of Apatinib Monotherapy for Unresectable, Metastatic Esophageal Cancer: A Single-Arm, Open-Label, Phase II Study.

LESSONS LEARNED: Patient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer. BACKGROUND: Apatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response. METHODS: This single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: Among 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11-7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥4 treatment-related AEs. CONCLUSION: Apatinib was effective as second- or further-line treatment for advanced esophageal cancer.

Identification of HGF as a novel target of miR-15a/16/195 in gastric cancer.

Background Gastric malignancy is the third most frequently encountered cancer globally and have been documented to confer extremely poor prognosis, given their limited treatment options. The up-regulation of hepatocyte growth factor (HGF) has been found in various tumor tissues, including GC tissue, and has been linked with tumor development. Nevertheless, the pathways leading to HGF upregulation have yet to be fully explored. Methods Immunohistochemistry (IHC) assay was used to detect HGF expression in human gastric tumor tissues, while western blotting allowed quantification of protein levels. Bioinformatics tools were used to predict potential miRNA that may target HGF mRNA. Relative levels of miR-15a/16/195 as well as the target mRNA levels were analyzed with qRT-PCR. Direct targeting between miRNA and mRNA was then validated by luciferase assay. Finally, a mouse xenograft tumor model was selected to demonstrate the in vivo effects of miR-15a/16/195. Results HGF protein expressions were markedly raised, while miR-15a/16/195 levels were dramatically down-regulated in tumor tissues of GC. miR-15a/16/195 were shown to directly bind with the 3'-UTR of HGF mRNA. This study demonstrated that HGF can be repressed by overexpressed miR-15a/16/195, which resulted in the suppression of GC cell proliferation and migration. Furthermore, in the xenograft mouse model, miR-15a/16/195 were also found to have a tumor growth suppression effect. Conclusions miR-15a/16/195 suppresses tumorigenesis by targeting HGF and may have a potential therapeutic application in the clinical treatment of GC.

Identification of Robinia pseudoacacia target proteins responsive to Mesorhizobium amphore CCNWGS0123 effector protein NopT.

Nodulation outer proteins secreted via type 3 secretion systems are involved in the process of symbiosis between legume plants and rhizobia. To study the function of NopT in symbiosis, we mutated nopT in Mesorhizobium amphore CCNWGS0123 (GS0123), which can nodulate black locust (Robinia pseudoacacia). The nopT mutant induced higher levels of jasmonic acid, salicylic acid, and hydrogen peroxide accumulation in the roots of R. pseudoacacia compared with wild-type GS0123. The ΔnopT mutant induced higher disease-resistant gene expression 72 hours post-inoculation (hpi), whereas GS0123 induced higher disease-resistant gene expression earlier, at 36 hpi. Compared with the nopT mutant, GS0123 induced the up-regulation of most genes at 36 hpi and the down-regulation of most genes at 72 hpi. Proteolytically active NopT_GS0123 induced hypersensitive responses when expressed transiently in tobacco leaves (Nicotiana benthamiana). Two NopT_GS0123 targets in R. pseudoacacia were identified, ATP-citrate synthase alpha chain protein 2 and hypersensitive-induced response protein. Their interactions with NopT_GS0123 triggered resistance by the plant immune system. In conclusion, NopT_GS0123 inhibited the host plant immune system and had minimal effect on nodulation in R. pseudoacacia. Our results reveal the underlying molecular mechanism of NopT function in plant-symbiont interactions.

Baicalin reverses radioresistance in nasopharyngeal carcinoma by downregulating autophagy.

BACKGROUND: Radiation resistance is the main cause of recurrence after radiotherapy, and increased autophagy after radiotherapy is related to radiotherapy resistance. This study aims to investigate the reversal effect of baicalin on radioresistance and its related mechanism. METHODS: CCK-8 and flow cytometry were used to detect the effect of proliferation and apoptosis by baicalin. Clone formation test was used to verify the effect of baicalin radiosensitization. Western blot analysis and electron microscopy were employed to observe the effect of baicalin on autophagy. RESULTS: Compared with the radiation therapy (RT) group, the RT combined baicalin (RT + BA) group showed a significantly low 2 Gy survival fraction of radiation therapy (P < 0.05). LC3-II protein expression in the RT group was significantly higher than which in the RT + BA group (P < 0.05). Electron microscopy showed that more autophagic vacuoles were observed in the RT group than those in the RT + BA group. CONCLUSIONS: Overall, baicalin can reverse the radioresistance of human nasopharyngeal carcinoma CNE-2R cells by downregulating RT-enhanced autophagy.

Comparative analysis of rhizobial chromosomes and plasmids to estimate their evolutionary relationships.

In the present study, complete genomic sequences retrieved from 57 rhizobial strains that covered four genera including 11 species were analyzed comprehensively. The four types of replicons: chromosomes, chromids, nonsymbiotic plasmids, and symbiotic plasmids were investigated and compared among these strains. Results showed that co-evolution occurred among these four replicons based on the similarities in average nucleotide identity. High correlation coefficient r values were observed between chromosomes and chromids, as well as between chromosomes and nonsymbiotic plasmids. Chromosomes and symbiotic plasmids showed different phylogenetic topology based on their core genes. Population structure analyses were performed to extrapolate the evolutionary histories of the test strains based on their chromosomal and symbiotic plasmid background. This resulted in seven ancestral types for chromosomal genes and three ancestral types for symbiotic plasmid genes. Rhizobial strains containing chromosome genes with ancestral type E tend to contain symbiotic plasmid genes with ancestral type II, while rhizobial strains containing chromosome genes with ancestral type G tend to contain symbiotic plasmid genes with ancestral type III. Seventeen strains associated with different host plant species which harbored the symbiotic genes with ancestral type I, exhibited high genetic diversity. In addition, Fu's test of the symbiotic plasmid genes with ancestral type III had undergone an expansion event, implying the influence of negative selection on these symbiotic plasmid genes.

A multi-center survey on dietary knowledge and behavior among inpatients in oncology department.

OBJECTIVE: To investigate the current associated factors of dietary knowledge and behavior, the intake and nutritional status in malignancy Chinese inpatients, and the malnutrition causes involved in dietary nutrition knowledge level and behavior, providing recommendations to patients for nutrition education and intervention. METHOD: Five hundred and thirty-five participants from 18 hospitals were investigated by a questionnaire related to dietary knowledge and behavior. Physicians asked and recorded the level of dietary intake and appetite scoring of the participants. The nutritional risk screening with the Nutritional Risk Screening 2002 (NRS-2002) and the dietary survey by 24 h dietary recalls were completed by a dietitian. Besides, the target energy intake and the target protein intake were calculated by the "rule of thumb" recommended by ESPEN guideline, comparing the difference between the actual intake and target intake. RESULTS: According to the questionnaire, 95.2% of participants thought it was important to have a good dietetic habit, and nearly half of them have searched for guides on how to diet; 70% of the patients had no clear idea of what was a scientific diet; 82% of patients had contradictory dietary knowledge; 64.2% of patients would listen to the opinion of the attending physician when a contradiction happened. The main three ways of learning about healthy diet were attending physician, network, and TV, respectively, with the values 26.0, 18.5, and 16.1%. Importantly, 99.6% of patients have made mistakes about dietary knowledge, for example, crab, chicken, lamb, fish, and prawns should not be eaten in their concept. In addition, more than 90% of participants have taken Ganoderma lucidum spore powder, sea cucumber, ginseng, Cordyceps sinensis, and so on. Ninety-three percent of the patients never reached a qualified nutrition education. Besides, 15.6% of the participants had nutritional risk (NRS-2002 ≥ 3). The actual daily energy intake was 1169.20 ± 465.97 kcal, which was significantly less than target energy intake (P < 0.01), amounting to 65.3% of the target requirements. The actual daily protein intake was 46.55 ± 21.40 g, which was significantly less than target protein intake (P < 0.01), amounting to 74.44%. On the other hand, 69% of the participants were "Not too bad, Ok, Good, or Very good" according to the records of physicians, while 34% of them did not reach 60%of the target requirements through dietary survey. CONCLUSION: The survey indicated that cancer patients had poor understanding of the scientific dietary nutrition and were in low level of normative nutritional education among Chinese malignancy inpatients. Dietary intake of most cancer patients decreased, and the actual intake cannot be revealed by NRS-2002 score or the physicians' inquiry. It is necessary to enhance the cooperation between dietitians and physicians and develop nutrition education to improve the level of dietary knowledge.

Lipid-soluble green tea extract: Genotoxicity and subchronic toxicity studies.

To assess the potential safety of lipid soluble green tea extract, also referred to as lipid soluble tea polyphenols (LSTP), a series of genotoxicity tests were conducted, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality test. The toxicity of LSTP was evaluated in 90- and 30-day feeding studies. LSTP did not show mutagenic activity in the Ames test and no genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). In the 90-day feeding study, LSTP was given in the diet at levels providing 0, 0.125, 0.25, or 0.50 g/kg bw/day. No significant effects were noted on body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathological examination. The no-observed-adverse-effect level (NOAEL) was therefore considered to be 0.50 g/kg bw/day, the highest dose tested. Likewise, dosing of SD rats by gavage for 30 days also showed no adverse effects of growth, hematology, clinical chemistry, organ weights, or histopathology at doses of 0.58, 1.17, and 2.33 g/kg bw/day. The NOAEL in the 30-day study was considered to be the highest dose tested. These data provide evidence to support the safe use of LSTP in food.

Synthesis and antitumor activity evaluation of novel ursolic acid derivatives.

Eleven novel ursolic acid (UA) derivatives were designed and synthesized with modification at positions of C-2, C-3, and C-28 of UA. Their structures were confirmed by MS, (1)H NMR, and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (HeLa, HepG2, and BGC-823) were evaluated by MTT assay. The results indicated that all compounds could inhibit cell proliferation of HeLa, HepG2, and BGC-823 cells. Among them, compounds I3 and I4 showed more potent cytotoxicity on these three tumor cells than gefitinib (positive control), worthy to be studied further.

[Advances in study of Survivin inhibitors].

Survivin, a member of the inhibitor of apoptosis proteins family, is considered to be an important target of anticancer treatment for its key role in the control of cell division and cell apoptosis. Currently, only a few Survivin inhibitors have been developed, and most of them reduce Survivin level by interacting with other biomolecules instead of directly interacting with Survivin protein. This review summarizes the structure of Survivin protein, the mechanism of action and research progress of Survivin inhibitors, which may has a great significance in the study of selective Survivin inhibitors in the future.

Global transcriptome analysis of Mesorhizobium alhagi CCNWXJ12-2 under salt stress.

BACKGROUND: Mesorhizobium alhagi CCNWXJ12-2 is a α-proteobacterium which could be able to fix nitrogen in the nodules formed with Alhagi sparsifolia in northwest of China. Desiccation and high salinity are the two major environmental problems faced by M. alhagi CCNWXJ12-2. In order to identify genes involved in salt-stress adaption, a global transcriptional analysis of M. alhagi CCNWXJ12-2 growing under salt-free and high salt conditions was carried out. The next generation sequencing technology, RNA-Seq, was used to obtain the transcription profiles. RESULTS: We have compared the transcriptome of M. alhagi growing in TY medium under high salt conditions (0.4 M NaCl) with salt free conditions as a control. A total of 1,849 differentially expressed genes (fold change ≧ 2) were identified and 933 genes were downregulated while 916 genes were upregulated under high salt condition. Except for the upregulation of some genes proven to be involved in salt resistance, we found that the expression levels of protein secretion systems were changed under high salt condition and the expression levels of some heat shock proteins were reduced by salt stress. Notably, a gene encoding YadA domain-containing protein (yadA), a gene encoding trimethylamine methyltransferase (mttB) and a gene encoding formate--tetrahydrofolate ligase (fhs) were highly upregulated. Growth analysis of the three gene knockout mutants under salt stress demonstrated that yadA was involved in salt resistance while the other two were not. CONCLUSIONS: To our knowledge, this is the first report about transcriptome analysis of a rhizobia using RNA-Seq to elucidate the salt resistance mechanism. Our results showed the complex mechanism of bacterial adaption to salt stress and it was a systematic work for bacteria to cope with the high salinity environmental problems. Therefore, these results could be helpful for further investigation of the bacterial salt resistance mechanism.

Increased lymphocyte to monocyte ratio is associated with better prognosis in patients with newly diagnosed metastatic nasopharyngeal carcinoma receiving chemotherapy.

Inflammation has been demonstrated to be widely involved in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the prognostic significance of lymphocyte to monocyte ratio (LMR) in metastatic NPC is not fully addressed. The purpose of the study is to investigate the prognostic impact of pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR on patients with newly diagnosed metastatic NPC undergoing chemotherapy. Between January 2006 and December 2010, patients with newly diagnosed metastatic NPC undergoing chemotherapy were retrospectively collected. The prognostic significance of baseline clinical features and inflammatory markers was investigated. A total of 256 patients were eligible for the study. The best cut-off value of ALC, AMC, and LMR was 2.25 × 10(9)/L, 0.35 × 10(9)/L, and 5.07, respectively. Patients in the high LMR group had a significantly longer overall survival (OS) (25.0 months [24.50-25.49]) than patients in the low LMR group (16.0 months [15.51-16.49]; p < 0.001). In addition, ALC ≥ 2.25 × 10(9)/L (HR, 0.59; 95% CI, 0.43-0.81; p = 0.001) and LMR ≥ 5.07 (HR, 0.42; 95% CI, 0.30-0.59; p < .001) remained as independent prognostic factors for superior OS, while AMC did not retained its prognostic significance in COX multivariate analysis. Pre-treatment ALC and LMR were demonstrated to be independent prognostic factors in patient with newly diagnosed metastatic NPC receiving chemotherapy. Future prospective studies are needed to validate the findings.

Clinicopathologic characteristics and survival of male breast cancer.

BACKGROUNDS: Male breast cancer (MBC) is a rare disease and accounts for <1 % of all breast cancers. METHODS: We retrospectively analyzed clinicopathologic characteristics and prognosis of MBC patients who were diagnosed in our hospital between March 2002 and March 2012. RESULTS: The median age of diagnosis of MBC was 62 years, which was 9 years older than female breast cancer (FBC) patients. The highest proportion of MBC patients was in the 50-59-year age group. The percentage of invasive ductal carcinoma in MBC was much higher than in FBC (P = 0.000). The positive rate of estrogen receptors in MBC patients (87.9 %) was significantly higher than in FBC patients (P = 0.048), whereas HER-2 was positive in 17.2 % of MBC patients, which was significantly lower than in FBC patients (P = 0.001). There was a consistent significant difference in luminal subtypes of FBC and MBC patients (P = 0.000). The overall survival rates of MBC were significantly higher than FBC (P = 0.004). HER-2-positive patients had a statistically worse prognosis than HER-2-negative patients (P = 0.040). Lymph node metastasis and larger tumor size were also associated with poorer prognosis (P = 0.056 and P = 0.088). The level of hormones was examined in 7 patients, and abnormal hormone levels were detected in 4. CONCLUSION: The FBC patients were significantly different from the MBC in clinicopathologic and prognostic characteristics. HER-2 positivity was an important factor for prognosis.