SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

Non-linear relationship between dietary vitamin E intake and cognitive performance in older adults.

OBJECTIVES: This study aimed to explore the relationship between dietary vitamin E (VE) intake and cognitive function in older adults. STUDY DESIGN: This was a cross-sectional study. METHODS: We applied data from the National Health and Nutrition Examination Survey obtained during 2011-2014 that met our requirements. The cognitive ability assessments included the Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests, the animal fluency test, the Digit Symbol Substitution Test, and a composite z-score calculated by summing z-scores of individual tests. We used binary logistic regression analysis to explore the relationship between VE intake and cognitive performance. The results are reported using odds ratios and 95% confidence intervals. Our study also included sex-stratified analyses and sensitivity analysis. A restricted cubic splines model was used to evaluate the dose-response relationship between dietary VE intake and cognitive function. RESULTS: This study found that a higher intake of dietary VE was associated with a lower risk of cognitive impairment in patients. Sensitivity analysis shows stable results. The results of the gender stratification analysis showed that dietary VE intake was negatively related to the risk of cognitive disorder among females. An irregular L-shaped dose-response relationship was observed between dietary VE intake and cognitive impairment risk. CONCLUSIONS: Dietary VE intake was negatively related to the risk of cognitive disorder in older adults, with a higher VE intake lowering the risk.

Differential uptake of nitrogen forms by two herbs in the Gurbantunggut desert, Central Asia.

Understanding how plants adjust their requirements for different N forms can help elucidate plant coexistence strategies in N-limited desert ecosystems. To understand the mechanisms involved, we investigated whether two desert herbs can directly absorb dissolved organic nitrogen (N) and tested whether the patterns changed over different growth stages. Two dominant herbaceous species, Astragalus arpilobus and Arnebia decumbens, from the southern edge of the Gurbantunggut desert, China, were selected. Short-term (24 h) 15 N-labelled tracer (15 N-NO3 , 15 N-NH4 , 2-13 C-15 N-Glycine) treatments were conducted at two soil depths (0-5 cm and 5-15 cm) in the season of rapid growth (June) and in the peak biomass season (July). Enrichment in 13 C and 15 N was assessed in the two species receiving glycine. The ratio 13 C:15 N was 0.21-1.39 at the 24-h harvest, suggesting that approximately 10.5-69.5% of glycine had been absorbed. The amount of absorbed 15 N was significantly affected by species, month, soil depth and N form. The two species absorbed most 15 N from the 0-5 cm soil layer, and the absorption rate in July was higher than that in June. The absorption of 15 N-NO3 and 15 N-NH4 was significantly higher than that of 2-13 C-15 N-Glycine. The results indicate that these herbs could use amino acids in the N-deficient desert ecosystem. The two co-existing species used different forms of inorganic N for their requirements and maintained a specific preference throughout various growth stages.

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

MiR-129-2 weakens proliferation and promotes apoptosis of liver cancer cells by suppressing the Wnt signaling pathway.

OBJECTIVE: To explore the effects of micro ribonucleic acid-129-2 (miR-129-2) on proliferation and migration of liver cancer cells and its possible mechanism. PATIENTS AND METHODS: The expression level of miR-129-2 was measured in liver cancer tissues and adjacent tissues from patients with liver cancer. Its level in liver cancer HepG2 cells and normal liver cells L-02 was also detected via quantitative polymerase chain reaction (qPCR). MiR-192-2 overexpression model was established in the HepG2 cell line. The proliferation and apoptosis levels of cells were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Wound healing assay was performed to detect the migration ability of cells. The expressions level of genes in the Wnt signaling pathway were measured through Western blotting. Xenograft tumor model was conducted in nude mice for exploring the in vivo effects of miR-129-2 on liver cancer growth. RESULTS: The expression level of miR-129-2 was significantly lower in liver cancer tissues than that in adjacent tissues (p<0.01), and it was overtly lower in HepG2 cells than that in L-02 cells (p<0.01). Overexpression of miR-129-2 weakened proliferation and migration abilities of liver cancer cells (p<0.01), and evidently increased apoptosis level (p<0.01). Sex-determining region Y-related HMG-box 4 (Sox4) and matrix metalloproteinase-2 (MMP-2) were downregulated, while phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) was upregulated in liver cancer cells overexpressing miR-129-2. Besides, the weight and volume of tumors in nude mice bearing liver cancer were significantly smaller after overexpression of miR-129-2. CONCLUSIONS: MiR-129-2 weakens proliferation and migration and stimulates apoptosis in liver cancer cells mainly by downregulating Sox4 and inactivating the Wnt signaling pathway.

Seasonal nitrogen uptake strategies in a temperate desert ecosystem depends on N form and plant species.

Symbiotic plants might be able to regulate a limited nitrogen (N) pool, thus avoiding and reducing competition for resources, through the uptake of different chemical N forms. Our aim was to see whether coexisting herbs showed preference for different forms of N in a temperate desert. We conducted a situ experiment using the 15 N labeling method in the Gurbantunggut Desert of Northwestern China dominated by Erodium oxyrrhynchum, Hyalea pulchella, Nonea caspica and Lactuca undulata during their growing period (April and May). Four desert herb species preferentially relied on 15 N-NO3 for their N nutrition. Multi-factor analysis of variance (ANOVA) analysis results showed that species, N forms, months, and soil depths strongly affected N uptake rate. The uptake rate by herbs was higher in May than in April, and higher at 0-5 cm than at 5-15 cm soil layers. Erodium oxyrrhynchum, N. caspica and L. undulata showed different preference on N form over months. Erodium oxyrrhynchum and L. undulata changed their uptake preference from more 15 N-Glycine in April to more 15 N-NH4 in May. Although the N uptake rate of four desert herbs varied across different soil depths and months, all species absorbed more inorganic N compared with organic N. The higher preference for 15 N-NO3 and 15 N-NH4 over 15 N-Gly possibly reflects adaptation to different N forms in temperate desert.

Comparing the efficacy of targeted next-generation sequencing in the identification of somatic mutations in circulating tumor DNA from different stages of lung cancer.

This study aims to assess the potential clinical application of targeted next generation sequencing (NGS)-based deep sequencing for the detection of clinically relevant mutations in circulating tumor DNA (ctDNA) obtained from non-small cell lung cancer (NSCLC) patients. Targeted deep sequencing was performed to identify High Confidence Somatic Variants (HCSVs) in matched tumor tissue DNA (tDNA) and ctDNA in 50 NSCLC patients. Our results demonstrated that NSCLC patients with Stage IV (61.5%) exhibited a higher concordance rate at the mutation level between plasma ctDNA and tDNA samples than those with Stage I-III (14.5%). Moreover, it is noteworthy that the allele frequency of these detected HCSVs in ctDNA increased with the advance in tumor stage. Besides, using tDNA as a reference, the sensitivity of plasma ctDNA analyzed by deep NGS for actionable EGFR was much higher in patients with Stage IV (66.6%) than those with Stage I-III (7.7%). In conclusion, it appears that ctDNA NGS-based deep sequencing is a feasible approach to identify mutations in patients with Stage IV NSCLC. However, additional methods with higher sensitivity and specificity are needed to improve the successful application of this platform in the earlier stages of NSCLC.

[Application of image-guided system in endoscopic sinus and skull base surgery].

Objective:To evaluate the applicative value of image-guided system in endoscopic sinus and skull base surgeries. Method:A total of 103 endoscopic surgical procedures were performed.All these procedures were conducted with the utilization of image-guided system, among which there were 92 cases of sinonasal-skull base surgery(including nasal sinuses resection of benign and malignant tumors involving skull base lesions, the cumulative orbital lesion resection of nasal sinus lesions, etc. ), 6 repair of cerebrospinal fluid leak, 3 pituitary adenoma resection, 2 traumatic neuropathy optic nerve decompression. Result:With the utilization of image-guided system, all patients had successful surgery without major and minor complications. The image-guided system provided high precision with short registration time. Conclusion:Image-guided system can help the surgeon to identify accurately the vital anatomic landmarks of sinus and skull base, improving surgical accuracy and safety as well as reducing or avoiding the intraoperative and postoperative complications.

[The role and mechanism of regulatory T cells in indirect acute lung injury].

Objective: To study the role and mechanism of CD(4)(+) CD(25)(+) FoxP3(+) regulatory T cells (Tregs) in the pathophysiological process of indirect acute lung injury (iALI) in mice. Methods: The iALI model was successfully induced by shock/cecal ligation and puncture method. Sham (n=8), cecal ligation and puncture (CLP, n=10), and hemorrhage (Hem, n=12) groups were established as controls. Two experimental groups were established: CLP+Hem (n=15) without Tregs adoptive transfer (AT), and CLP+Hem with Tregs adoptive transfer (CLP+Hem+AT, n=14). The number of Tregs, subsets of lymphocytes, neutrophil activity, apoptosis, cytokine levels and histopathological changes were measured in the lung tissue of each group. The protein exudation and the expression of IL-10 in bronchoalveolar lavage fluid (BALF) were also detected. After in vitro cell co-culture, the proliferation of activated T cells and the expression of IL-10, INF-γ and iNOS protein were detected. Results: The percentage and the absolute cell number of CD(4)(+) CD(25)(+) FoxP3(+) Tregs in lung tissue of iALI mice were (2.530±0.086)%, and (1.441±0.090)×10(4)/ml, respectively, which were significantly higher than the control groups (P<0.05). Adoptive transfer of Tregs could significantly decrease CD3-positive T lymphocytes, myeloperoxidase (MPO) activity, caspase-3 activity in lung tissue as well as protein leakage in BALF (P<0.05). Meanwhile interleukin-10 (IL-10) levels in lung tissue and BALF were up-regulated from (121.4±43.76) pg/ml to (201.0±61.96) pg/ml (t=2.776, P<0.05) and (206.2±90.88) pg/ml to (339.4±109.5) pg/ml (t=2.477, P<0.05), respectively. Histopathology was also significantly improved. The proliferation of activated T lymphocytes in the adoptive transfer Treg (AT-Treg) group (n=5) was significantly lower than that in the natural regulatory T cell (N-Treg) group (n=5, t=7.485, P<0.01) and the negative control group (n=5, t=16.66, P<0.01). However, iNOS enzyme inhibitor L-NMMA could significantly reduce the T cell proliferation (P<0.05). Conclusion: CD(4)(+)CD(25)(+)FoxP3(+) Tregs could reduce inflammatory reaction in mice with iALI, and the iNOS signaling pathway may be involved in this process.

[Clinical features of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions-single-center study].

Objective: To analyze the clinical characteristics, treatment methods and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 tRCC). Methods: From January 2007 to February 2018, 48 patients were diagnosed with Xp11.2 tRCC at Nanjing Drum Tower Hospital. The epidemiological features, treatment methods and long-term follow-up results were retrospectively reviewed. Results: Of the 48 patients, 20 cases were female and 28 cases were male, aged from 2 to 72 years. Gross hematuria and flank pain were the most frequent symptoms, which occurred on 14 cases and 8 cases respectively. The mean tumor size of 48 cases was (5.3±2.5)cm. Among the 34 cases who were classified as stageⅠ/Ⅱ, 14 cases received laparoscopic nephron-sparing surgery(NSS)and 20 cases received radical nephrectomy(RN). The other 14 cases who were classified as stage Ⅲ/Ⅳ received RN but one case received target therapy. On univariate analysis, tumor diameter, adjuvant treatment, AJCC stage, lymph node metastasis and vein tumor thrombosis showed association with progression-free survival (PFS) and overall survival (OS) (P<0.05). Multivariate analysis indicated that AJCC stage (P=0.023, 95% CI: 0.048-0.081)and vein tumor thrombosis (P=0.046, 95% CI: 1.004-1.590)were independent prognostic factors of PFS. Conclusions: Xp11.2 tRCC mainly occurs in females. RN was the major method for Xp11.2 tRCC. However, NSS can also receive satisficed results for stage T1a case. High AJCC stage and the occurrence of vein tumor thrombosis indicated poor prognosis.

Discovery of a second species of Hyalocylindrophora and the phylogenetic position of the genus in Bionectriaceae.

A new holomorphic species, Hyalocylindrophora bispora, is described and illustrated based on a collection on rotten branches from Guangdong Province, China. The fungus is characterized by fleshy perithecia that become deeply cupulate when dry, covered with long and stiff hairs on the surface, and not change color in KOH or lactic acid. Asci are two-spored and evanescent at maturity. Ascospores are ellipsoidal to elongate-ellipsoidal, unicellular, and warted. Conidiogenous cells are phialidic and cylindrical. Conidia are thick-walled, unicellular, ellipsoidal to somewhat lemon-shaped. This is the first report of sexual state for Hyalocylindrophora. The phylogenetic position of the genus in Bionectriaceae is confirmed by sequence analyses of the combined nuc rDNA 28S, α-actin, and DNA-directed RNA polymerase II subunit 1 regions. Distinctions between the new taxon and the only known species of the genus are compared.

Evolution and characterisation of the AhRAF4 NB-ARC gene family induced by Aspergillus flavus inoculation and abiotic stresses in peanut.

Aflatoxin contamination in peanut is a serious food safety issue to human health around the world. Finding disease resistance genes is a key strategy for genetic improvement in breeding to deal with this issue. We identified an Aspergillus flavus-induced NBS-LRR gene, AhRAF4, using a microarray-based approach. By comparison of 23 sequences from three species using phytogenetics, protein secondary structure and three-dimensional structural analyses, AhRAF4 was revealed to be derived from Arachis duranensis by recombination, and has newly evolved into a family of several members, characterised by duplications and point mutations. However, the members of the family descended from A. ipaensis were lost following tetraploidisation. AhRAF4 was slightly up-regulated by low temperature, drought, salicylic acid and ethylene, but down-regulated by methyl jasmonate. The distinct responses upon As. flavus inoculation and the differential reactions between resistant and susceptible varieties indicate that AhRAF4 might play a role in defence responses. Temporal and spatial expression and the phenotype of transformed protoplasts suggest that AhRAF4 may also be associated with pericarp development. Because tetraploid cultivated peanuts are vulnerable to many pathogens, an exploration of R-genes may provide an effective method for genetic improvement of peanut cultivars.

Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1.

Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.

4218T/C polymorphism associations with post-cesarean patient-controlled epidural fentanyl consumption and pain perception.

BACKGROUND: The utilization of intrathecal opioids is an efficacious component of post-cesarean section pain management. Given that growing evidence indicates that calcitonin gene-related peptide (CGRP) plays a key role in the development of peripheral sensitization and is associated with enhanced pain, we hypothesized that CGRP 4218T/C polymorphism is associated with the variability in fentanyl consumption for post-cesarean analgesia. METHODS: We recruited 548 patients who presented for elective cesarean delivery, and used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze CGRP 4218T/C polymorphism. We examined the association of CGRP 4218T/C polymorphism and post-operative fentanyl consumption for analgesia as well as adverse reactions to fentanyl in those patients who received cesarean section surgeries. RESULTS: We found that the CGRP 4218T/C polymorphism has a significant effect on pain perception, analgesic requirement, and nausea and vomiting for the first 24 h after cesarean delivery in patients who received PCEA fentanyl. Individuals with the C/C genotype had more pain, required more PCEA fentanyl, and experienced a lower incidence of nausea and vomiting. CONCLUSION: These results indicated that patients with C/C genotype may have reduced sensitivity to fentanyl analgesia and/or increased pain perception, and were more willing to use PCEA fentanyl to manage their pain.

[Comparison of the effects of total hip arthroplasty via direct anterior approach and posterolateral piriformis-sparing approach].

OBJECTIVE: To compare the clinical effects of direct anterior approach (DAA) and posterolateral piriformis-sparing approach (Mis-PLA) for minimally invasive surgery of total hip arthroplasty. METHODS: The patients who had total hip arthroplasty from March 2015 to February 2016 were randomly divided into 2 groups: DAA group and Mis-PLA group. In the study, 43 patients (45 hips) were performed with total hip replacement via the direct anterior approach (DAA group). As comparison, 39 patients (42 hips) were performed with total hip replacement via the posterolateral piriformis-sparing approach (Mis-PLA group) at the same period. DAA group: 27 male patients (27 hips), and 16 female patients (18 hips), with an average age of (57.4±7.3) years, preoperative Harris score (41.4±8.7), body mass index (BMI) (24.3±2.2) kg/m2; Mis-PLA group: 25 male patients (26 hips), 14 female patients (16 hips), with an average age of (59.2±7.3) years, preoperative Harris score (39.6±8.4), BMI (24.7±2.5) kg/m2. The length of incision, operation time, blood loss, postoperative Harris score were observed and specially the hip functional recovery was fully assessed. RESULTS: (1) All the incisions healed by first intention. No complications were found in both groups. The length of incision:DAA group: (9.2±0.7) cm and Mis-PLA group: (9.5±0.6) cm. No statistical significant differences were found (P=0.053). The operation time:DAA group (74.3±10.1) min and Mis-PLA group (37.5±4.3) min, which showed statistically significant differences (P<0.01). Blood loss: DAA group (229.6±79.2) mL and Mis-PLA group (215.7±56.0) mL. No statistical significant differences were found (P=0.366). (2) The patients in both groups were followed up for 6-12 months. The Harris hip scores for 6 weeks' follow-up: (85.5±4.1) in DAA group and (79.0±4.4) in Mis-PLA group, which indicated statistically significant differences (P<0.01). The Harris scores for the 6-month follow-up: (94.3±2.7) in DAA group and (95.2±1.9) in Mis-PLA group. No statistically significant differences were found (P=0.125). The basic daily hip function analysis for the 6-week follow-up: walking speed: no statistically significant differences were found between the two groups (P=0.298); Climbing stairs: Mis-PLA group' outcome was better than DAA group's with statistical differences (P=0.047); Circling, sitting and wearing shoes and socks: outcomes in DAA group exceeded Mis-PLA group's with statistically significant differences (P<0.01, P=0.016, P<0.01). CONCLUSION: Total hip arthroplasty through either DAA or Mis-PLA approaches could result in very satisfactory clinical effect. Comparing with DAA, Mis-PLA requires less operation time, shorter learning curve,which indicates that it is a relatively safer approach. The advantages of total hip arthroplasty through direct anterior approach lie in less positional limitation in the early stage of postoperative period, as well as a faster recovery of hip function.

Efficient biosynthesis of d-ribose using a novel co-feeding strategy in Bacillus subtilis without acid formation.

Normally, low d-ribose production was identified as responsible for plenty of acid formation by Bacillus subtilis due to its carbon overflow. An approach of co-feeding glucose and sodium citrate is developed here and had been proved to be useful in d-ribose production. This strategy is critical because it affects the cell concentration, the productivity of d-ribose and, especially, the formation of by-products such as acetoin, lactate and acetate. d-ribose production was increased by 59·6% from 71·06 to 113·41 g l-1 without acid formation by co-feeding 2·22 g l-1  h-1 glucose and 0·036 g l-1  h-1 sodium citrate to a 60 g l-1 glucose reaction system. Actually, the cell density was also enhanced from 11·51 to 13·84 g l-1 . These parameters revealed the importance of optimization and modelling of the d-ribose production process. Not only could zero acid formation was achieved over a wide range of co-feeding rate by reducing glycolytic flux drastically but also the cell density and d-ribose yield were elevated by increasing the hexose monophosphate pathway flux. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus subtilis usually produce d-ribose accompanied by plenty of organic acids when glucose is used as a carbon source, which is considered to be a consequence of mismatched glycolytic and tricarboxylic acid cycle capacities. This is the first study to provide high-efficiency biosynthesis of d-ribose without organic acid formation in B. subtilis, which would be lower than the cost of separation and purification. The strain transketolase-deficient B. subtilis CGMCC 3720 can be potentially applied to the production of d-ribose in industry.

Determinants of Gefitinib toxicity in advanced non-small cell lung cancer (NSCLC): a pharmacogenomic study of metabolic enzymes and transporters.

Skin rash, diarrhea and hepatotoxicity are the most common toxicities of Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The present study investigated the effects of genetic polymorphisms of drug target, metabolizing enzymes and transporters on Gefitinib toxicities. Thirty single-nucleotide polymorphisms, including EGFR, cytochromes P450 and ATP-binding cassette (ABC), were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform in 59 non-small cell lung cancer patients treated with Gefitinib. Correlation analyses were performed to evaluate their effects on Gefitinib-induced toxicities. ABCB1 rs1128503 TT genotype was a significant high-risk determinant of both skin rash and diarrhea, with 15.78- and 10.78-fold of incident risk increased, respectively. (odds ratio (OR)=15.78, 95% confidence interval (CI) 2.01-124.1, P=0.0087; OR=10.78, 95% CI 1.54-75.40, P=0.0166 vs non-TT genotypes). Patients with ABCB1 rs1128503 TT genotype had greater risk of skin rash and diarrhea. Therefore, polymorphism analyses of ABCB1 might be beneficial to optimize Gefitinib treatment.

Revision of the genus Thyronectria (Hypocreales) from China.

Recent collections and herbarium specimens of Thyronectria from different regions in China were examined. Using combined analyses of morphology and molecular data, we recognized eight species. Among them, Thyronectria atrobrunnea, T. orientalis, and T. sinensis are described and illustrated as new species. Thyronectria atrobrunnea is characterized by blackish brown perithecia that become cupulate when dry, and 8-spored asci containing ellipsoidal to broadly fusiform or subcylindrical ascospores that bud to form bacillar to subellipsoidal ascoconidia within the asci. Thyronectria orientalis can be easily recognized by stromata that are erumpent through the epidermis of the host, immersed or semi-immersed perithecia covered with yellowish green scurf, and ellipsoidal to subfusiform, muriform ascospores. Thyronectria sinensis on Pinus features solitary ascomata that are rarely aggregated, and 8-spored asci giving rise to subcylindrical to vermiform, multiseptate ascospores that form bacillar to allantoid ascoconidia that fill the asci. The new species and their close relatives are compared and differences between them are discussed. Thyronectria strobi is reported for the first time in China. Name changes for the previously recorded species are noted. Phylogenetic analyses inferred from 28S, ITS, RPB1, TEF1, and TUB2 hint that phenotypic characters, viz. stromata, ascospores, appendage of perithecial wall, and host specificity may carry phylogenetic information as previous papers discussed.

[The immunological effects of phthalanilic acid on mice].

OBJECTIVE: To explore the effects of phthalanilic acid on immune system in mice from the respects of blood, tissues, cell and cytokines. And to find sensitive index of immunological effects and offer experimental data for toxicological safety evaluation. METHODS: 60 balb/c mice were randomly divided into 4 groups. The mice in control group were given soybean oil. The mice in group 2 to 4 were given phthalanilic acid at dose 30 mg/kg, 100 mg/kg and 300 mg/kg by gavage respectively for 28 days. After 24 hours of the last contamination, the histopathology of spleen and thymus, immunologic factors and cell multiplication of lymphocyte were analysed. The data were analysed by SPSS. RESULTS: After contamination for 28 days, 300 mg/kg phthalanilic acid could cause that the cell multiplication of lymphocyte were inhibited. Spleens were damaged at the dose of 100 mg/kg. The concentration of IFN-γ and IL-4[ (843.31±14.81) pg/ml and (1174.44±7.32) pg/ml] in thymus were increased significantly (P<0.05) at the dose of 30 mg/kg. CONCLUSION: Different doses of phthalanilic acid may damnify the immune system of mice at different degrees for 28 days continuous contamination. Phthalanilic acid might have immunotoxicity.