First case report of ensartinib in a patient with metastatic ALK rearranged lung cancer with ALK I1171N mutation: a case report.

BACKGROUND: The acquired resistance to ALK tyrosine kinase inhibitors (TKIs) in ALK-rearranged NSCLC is associated with poor survival outcomes and poses distinct clinical challenges. It is essential to develop potential therapeutic strategies for overcoming resistance. CASE PRESENTATION: Here, we first report a female lung adenocarcinoma patient with an acquired ALK resistance mutation (ALK 11171N) who was treated with ensartinib. Her symptoms significantly improved after only 20 days, and with a side effect of mild rash. Follow-up images observed no further brain metastases after 3 months. CONCLUSIONS: This treatment may provide a new therapeutic strategy for ALK TKIs resistant patients, especially in position 1171 of ALK exon20.

Comparative physiology and transcriptome analysis reveals that chloroplast development influences silver-white leaf color formation in Hydrangea macrophylla var. maculata.

BACKGROUND: Hydrangea macrophylla var. Maculata 'Yinbianxiuqiu' (YB) is an excellent plant species with beautiful flowers and leaves with silvery white edges. However, there are few reports on its leaf color characteristics and color formation mechanism. RESULTS: The present study compared the phenotypic, physiological and transcriptomic differences between YB and a full-green leaf mutant (YM) obtained from YB. The results showed that YB and YM had similar genetic backgrounds, but photosynthesis was reduced in YB. The contents of pigments were significantly decreased at the edges of YB leaves compared to YM leaves. The ultrastructure of chloroplasts in the YB leaves was irregular. Transcriptome profiling identified 7,023 differentially expressed genes between YB and YM. The expression levels of genes involved in photosynthesis, chloroplast development and division were different between YB and YM. Quantitative real-time PCR showed that the expression trends were generally consistent with the transcriptome data. CONCLUSIONS: Taken together, the formation of the silvery white leaf color of H. macrophylla var. maculata was primarily due to the abnormal development of chloroplasts. This study facilitates the molecular function analysis of key genes involved in chloroplast development and provides new insights into the molecular mechanisms involved in leaf coloration in H. macrophylla.

Emergent Protective Organogenesis in Date Palms: A Morpho-Devo-Dynamic Adaptive Strategy during Early Development.

Desert plants have developed mechanisms for adapting to hostile desert conditions, yet these mechanisms remain poorly understood. Here, we describe two unique modes used by desert date palms (Phoenix dactylifera) to protect their meristematic tissues during early organogenesis. We used x-ray micro-computed tomography combined with high-resolution tissue imaging to reveal that, after germination, development of the embryo pauses while it remains inside a dividing and growing cotyledonary petiole. Transcriptomic and hormone analyses show that this developmental arrest is associated with the low expression of development-related genes and accumulation of hormones that promote dormancy and confer resistance to stress. Furthermore, organ-specific cell-type mapping demonstrates that organogenesis occurs inside the cotyledonary petiole, with identifiable root and shoot meristems and their respective stem cells. The plant body emerges from the surrounding tissues with developed leaves and a complex root system that maximizes efficient nutrient and water uptake. We further show that, similar to its role in Arabidopsis (Arabidopsis thaliana), the SHORT-ROOT homolog from date palms functions in maintaining stem cell activity and promoting formative divisions in the root ground tissue. Our findings provide insight into developmental programs that confer adaptive advantages in desert plants that thrive in hostile habitats.

Efficacy and safety of recombinant human lymphotoxin-α derivative with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-label, controlled, phase 2b trial.

BACKGROUND: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative that is missing 27 N-terminal amino acid residues. Previous studies indicated a benefit from the addition of rhLTα-Da to cisplatin-based treatment in patients with metastatic esophageal squamous cell carcinoma. The current study was conducted to evaluate the efficacy and safety of rhLTα-Da plus cisplatin and fluorouracil (PF) in patients with mESCC. METHODS: Patients from 15 centers in China were randomly assigned (1:1:1) to 3 arms (arm A, PF plus 10 µg/m2 daily rhLTα-Da; arm B, PF plus 20 µg/m2 daily rhLTα-Da; arm C, PF alone). The primary endpoints included progression-free survival (PFS) and the confirmed overall response rate (ORR). An exploratory analysis was performed to evaluate the role of serum tumor necrosis factor receptor II (TNFR II) in predicting the efficacy of rhLTα-Da. RESULTS: Between September 2010 and May 2013, 150 patients were enrolled. No significant differences in either PFS or ORR were observed between the 3 arms. However, in a small subset of patients who had low serum TNFR II levels, the median PFS was significantly longer for those in arm B than for these in other 2 arms (7.2 months [95% confidence interval, 5.1-8.6 months] for arm B vs 3.5 months [95% confidence interval, 1.7-5.5 months] for arm A [P = .022] and 4.0 months [95% confidence interval, 3.2-6.3 months] for arm C [P = .027]). The addition of rhLTα-Da significantly increased the incidence of chills (P < .001). CONCLUSIONS: rhLTα-Da combined with the PF regimen failed to improve PFS and ORR in patients with mESCC, except in a small subset that had low serum TNFR II concentrations. Cancer 2017;123:3986-94. © 2017 American Cancer Society.

De novo characterization of the Iris lactea var. chinensis transcriptome and an analysis of genes under cadmium or lead exposure.

Iris lactea var. chinensis (I. lactea var. chinensis) is tolerant to accumulations of cadmium (Cd) and lead (Pb). In this study, the transcriptome of I. lactea var. chinensis was investigated under Cd or Pb stresses. Using the gene ontology database, 31,974 unigenes were classified into biological process, cellular component and molecular function. In total, 13,132 unigenes were involved in enriched Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and the expression levels of 5904 unigenes were significantly changed after exposure to Cd or Pb stresses. Of these, 974 were co-up-regulated and 1281 were co-down-regulated under the two stresses. The transcriptome expression profiles of I. lactea var. chinensis under Cd or Pb stresses obtained in this study provided a resource for identifying common mechanisms in the detoxification of different heavy metals. Furthermore, the identified unigenes may be used for the genetic breeding of heavy-metal tolerant plants.

The heterologous expression of the Iris lactea var. chinensis type 2 metallothionein IlMT2b gene enhances copper tolerance in Arabidopsis thaliana.

Iris lactea var. chinensis (I. lactea var. chinensis) is a widely adapted perennial species with a high level of copper tolerance. To evaluate the role of metallothioneins (MTs) in copper tolerance in I. lactea var. chinensis, a full-length cDNA homologue of MT2, designated IlMT2b (GenBank accession No. AB907788), was cloned using the RACE-PCR method. The expression level of IlMT2b in the leaves and roots of I. lactea var. chinensis was induced in response to copper (Cu) treatment. Ectopic expression of IlMT2b in Arabidopsis thaliana increased the Cu concentration and reduced H2O2 production in the transgenic plants. After treatment with 50 and 100 µM Cu, the root length of two transgenic seedlings was respectively about 1.5- and 3-fold longer than that of the wild-type. Together, these results suggested that IlMT2b may represent a useful target gene for the phytoremediation of Cu-polluted soil.

Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study.

BACKGROUND: To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. METHODS: One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46-50 Gy, at the end of RT, and 3-4 months after RT. RESULTS: Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse-free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). CONCLUSIONS: PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor tumor regression at the end of RT.

Overexpression of Iris. lactea var. chinensis metallothionein llMT2a enhances cadmium tolerance in Arabidopsis thaliana.

Metallothioneins (MTs) are cysteine-rich, low molecular weight, heavy metal-binding protein molecules. Here, a full-length cDNA homologue of MT2a (type 2 metallothionein) was isolated from the cadmium-tolerant species Iris. lactea var. chinensis (I. lactea var. chinensis). Expression of IlMT2a in I. lactea var. chinensis roots and leaves was up-regulated in response to cadmium stress. When the gene was constitutively expressed in Arabidopsis thaliana (A. thaliana), root length of transgenic lines was longer than that of wild-type under 50µM or 100µM cadmium stress. However, there was no difference of cadmium absorption between wild-type and trangenic lines. Histochemical staining by 3,3-diaminobenzidine (DAB) and nitroblue tetrazoliu (NBT) clearly demonstrated that transgenic lines accumulated remarkably less H2O2 and O2(-) than wild-type. Together, IlMT2a may be a promising gene for the cadmium tolerance improvement.

Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma.

BACKGROUND: To evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC). METHODS: Three hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD. RESULTS: Median follow-up was 66 months (range, 2-82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30-50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30-50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172). CONCLUSIONS: Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging.

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Background: Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC. Objectives: We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy. Design: Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection. Methods: This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system. Results: Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC-, KIT-CTC, and KIT+CTC at baseline (p = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95). Conclusions: CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation. Trial registration: NCT01740804.

Diagnostic Value of Abdominal B-Ultrasound for Congenital Heart Disease Complicated with Extracardiac Malformation in the Second Trimester of Pregnancy.

Objective: To explore the diagnostic value of abdominal B-ultrasound in the diagnosis of congenital heart disease complicated with extracardiac malformations in the second trimester of pregnancy. Methods: 50 pregnant women with congenital cardiac malformations and extracardiac malformations diagnosed in our hospital from 2015 to 2019 were retrospectively analyzed. The diagnostic results and the types of congenital heart disease complicated with extracardiac malformations were compared to analyze the diagnostic value of abdominal B-ultrasound. Results: In the diagnosis of 50 fetuses with congenital heart disease and extracardiac malformation, the tetralogy of Fallot syndrome accounts for the largest proportion. Abdominal B-ultrasound in the second trimester was associated with a higher detection rate of fetal heart malformation (72%) versus in the third trimester (40%) (P < 0.05). The single atrium and single ventricle had the highest diagnostic accuracy of fetal congenital heart malformation in the second trimester. The highest success rate of detection at different gestational weeks was observed at the 14th gestational week (P < 0.05). Four-chamber cardiac section (4CV) had the lowest diagnostic accuracy (62%) for cardiac malformations, and the 4CV + three-vessel-trachea plane (3VVT) had the highest diagnostic accuracy (90%) for cardiac malformations. Conclusion: Abdominal B-ultrasound features a high diagnostic value for congenital heart disease complicated with extracardiac malformations in the second trimester of pregnancy, and the second trimester is the optimal detection timing with the highest detection accuracy.

Biochemistry and transcriptome analyses reveal key genes and pathways involved in high-aluminum stress response and tolerance in hydrangea sepals.

Hydrangea [Hydrangea macrophylla (Thunb.) Ser.] is a high aluminum-tolerant ornamental plant species, which has a specific characteristic of color change, ie. some cultivars' floral color will change from red to blue or blue-violet planted in acidic soil containing aluminum. This study aims to understand the complex molecular mechanisms of floral color change under Al stress, through comparative biochemistry and transcriptome analyses between an Al3+-sensitive cultivar 'Bailer' and insensitive cultivar 'Ruby' under Al-stress. The results of biochemistry analysis showed that 'Bailer' displayed higher contents of Al3+ and delphinium-3-O-glucoside than that of 'Ruby' after Al2(SO4)3 treating. Meanwhile, the transcriptome analysis of different tissues identified 12,321 differentially expressed genes (DEGs) in 'Bailer' and 6,703 in 'Ruby'. Transcriptome analysis showed that changes in genes' expression pattern in several genes and pathways [such as including metal transporters, reactive oxygen species (ROS) scavenging enzyme, plant hormone signal transduction and favonoid biosynthesis pathway] were the key contributors to the Al3+-sensitive cultivar 'Bailer'. Besides, gene co-expression network analysis (WGCNA) demonstrated that five hub genes, including ABC transporters (TRINITY_DN1053_c0_g1, TRINITY_DN3377_c0_g2), cationic amino acid transporter (TRINITY_DN9684_c0_g2), oligopeptide transporter (TRINITY_DN1147_c0_g2) and flavonol synthase (TRINITY_DN15902_c0_g1), played vital roles in the networks regulating Al tolerance in hydrangea. Furthermore, HmABCI17's (TRINITY_DN1053_c0_g1) expression enhanced Al tolerance in yeast. The conclusions of this study are helpful to elucidate the differences and molecular mechanisms of different hydrangea cultivars on Al tolerance, and provide new insights into molecular assisted-screening for breeding blue flowers in hydrangea and other ornamental plants.

Identification of aluminum-activated malate transporters (ALMT) family genes in hydrangea and functional characterization of HmALMT5/9/11 under aluminum stress.

Hydrangea (Hydrangea macrophylla (Thunb.) Ser.) is a famous ornamental plant species with high resistance to aluminum (Al). The aluminum-activated malate transporter (ALMT) family encodes anion channels, which participate in many physiological processes, such as Al tolerance, pH regulation, stomatal movement, and mineral nutrition. However, systematic studies on the gene family have not been reported in hydrangea. In this study, 11 candidate ALMT family members were identified from the transcriptome data for hydrangea, which could be divided into three clusters according to the phylogenetic tree. The protein physicochemical properties, phylogeny, conserved motifs and protein structure were analyzed. The distribution of base conservative motifs of HmALMTs was consistent with that of other species, with a highly conserved WEP motif. Furthermore, tissue-specific analysis showed that most of the HmALMTs were highly expressed in the stem under Al treatment. In addition, overexpression of HmALMT5, HmALMT9 and HmALMT11 in yeasts enhanced their tolerance to Al stress. Therefore, the above results reveal the functional role of HmALMTs underlying the Al tolerance of hydrangea. The present study provides a reference for further research to elucidate the functional mechanism and expression regulation of the ALMT gene family in hydrangea.

Case Report: Durable partial response to icotinib plus crizotinib in a lung adenocarcinoma patient with double uncommon EGFR G719D/L861Q mutations and an acquired novel CUX1-MET fusion.

Non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping or high MET amplification display a high rate of response to MET inhibitors. However, MET fusions in NSCLC have rarely been revealed. In this report, a 63-year-old woman with lung adenocarcinoma (LADC), harboring EGFR exon 18 G719D and exon 21 L861Q mutations, received first-generation, EGFR-tyrosine kinase inhibitor (TKI) icotinib therapy. Next generation sequencing (NGS) results only displayed an EGFR T790M point mutation following icotinib resistance. Thus, the patient was treated with osimertinib and achieved a stable disease (SD). However, disease progressed after 15 months and a novel MET fusion (CUX1 exon14-MET exon15) in addition to EGFR G719D/L861Q mutations were simultaneously detected in a tissue biopsy sample. After more than nine months, the patient subsequently achieved a PR with the combination of icotinib and crizotinib. To our knowledge, this is the first case of LADC patient displaying the presence of EGFR double uncommon mutations and an acquired novel CUX1-MET fusion that has benefited from icotinib plus crizotinib treatment. Following nine months of PR with icotinib plus crizotinib, the patient, until the time of publication, is exhibiting stable disease. The results suggest that the CUX1-MET fusion may be sensitive to crizotinib, although previous reports indicated that some MET fusion cases did not respond to crizotinib. Given this disparity, distinguishing MET fusion partners when crizotinib is used in LADC treatment is also very important.

The genome of single-petal jasmine (Jasminum sambac) provides insights into heat stress tolerance and aroma compound biosynthesis.

Jasmine [Jasminum sambac (L.) Aiton] is a commercially important cultivated plant species known for its fragrant flowers used in the perfume industry, medicine and cosmetics. In the present study, we obtained a draft genome for the J. sambac cultivar 'Danbanmoli' (JSDB, a single-petal phenotype). We showed that the final genome of J. sambac was 520.80 Mb in size (contig N50 = 145.43 kb; scaffold N50 = 145.53 kb) and comprised 35,363 genes. Our analyses revealed that the J. sambac genome has undergone only an ancient whole-genome duplication (WGD) event. We estimated that the lineage that has given rise to J. sambac diverged from the lineage leading to Osmanthus fragrans and Olea europaea approximately 31.1 million years ago (Mya). On the basis of a combination of genomic and transcriptomic analyses, we identified 92 transcription factors (TFs) and 206 genes related to heat stress response. Base on a combination of genomic, transcriptomic and metabolomic analyses, a range of aroma compounds and genes involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways were identified. In the newly assembled J. sambac genome, we identified a total of 122 MYB, 122 bHLH and 69 WRKY genes. Our assembled J. sambac JSDB genome provides fundamental knowledge to study the molecular mechanism of heat stress tolerance, and improve jasmine flowers and dissect its fragrance.

[Retracted] miR­663 promotes NPC cell proliferation by directly targeting CDKN2A.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell cycle assay data shown in Figs. 2D and 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 4863­4870, 2017; DOI: 10.3892/mmr.2017.7129].

The embryo rescue derived intergeneric hybrid between chrysanthemum and Ajania przewalskii shows enhanced cold tolerance.

Five intergeneric hybrids between the chrysanthemum cultivar 'Zhongshanjingui' (as female) and Ajania przewalskii (as male) were obtained with the help of embryo culture. While 'Zhongshanjingui' bears a standard anemone type flower and A. przewalskii a non-anemone type one, the inflorescence type of the hybrids varied. The diameter of the hybrids' flowers was intermediate between those of the parents. The chromosome number of the hybrids was 2n = 45, of which GISH analysis was able to establish that 27 were inherited from 'Zhongshanjingui' and the other 18 from A. przewalskii. A combination of various assays was used to show that the cold tolerance of the hybrids was equivalent to that of the highly tolerant A. przewalskii parent. Enhanced cold tolerance was correlated with an increase in free proline and a decrease in malondialdehyde content.

Efficacy of the FOLFOX/CAPOX regimen for advanced small bowel adenocarcinoma: a three-center study from China.

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy, and most patients present with unresectable or metastatic disease. Thus far, no standard chemotherapeutic regimen has been established and related data are scarce, especially in Eastern countries. The purpose of this multicenter study was to evaluate the efficacy and toxicity of oxaliplatin combined with fluoropyrimidines in Chinese patients with advanced SBA. METHODS: Advanced SBA patients who received FOLFOX (5-fluorouracil/5-FU plus leucovorin and oxaliplatin)/ CAPOX (capecitabine plus oxaliplatin) as first-line chemotherapy between February, 2004 and October, 2010 were identified from 3 large medical centers in China. The response rate (RR), progression-free survival (PFS), overall survival (OS), and chemotherapy-associated toxicity were evaluated. Cox models were applied for multivariate analyses. RESULTS: Of 34 patients, with SBA 28 received FOLFOX and 6 CAPOX. The objective response (OR) and disease control (DC) rates were 32.3% and 61.7%, respectively. The median PFS and OS were 6.3 and 14.2 months, respectively. The toxicity was tolerable, grade 3-4 toxicity was rare. In multivariate analysis, only multi-organ metastasis reached borderline significance for shorter PFS (p=0.059), but the variables of age (>65 years; p=0.001), and multi-organ metastasis (p=0.001) were significantly associated with poor OS. CONCLUSION: To our knowledge, this multicenter retrospective study is the first and largest one among Asian studies at present estimating oxaliplatin combined with fluoropyrimidines as first-line chemotherapy for advanced SBA. FOLFOX/CAPOX is proved effective for advanced SBA in this study, but the results do not absolutely agree with previous studies from Western countries, showing that further studies are still needed.

An integrated transcriptomic and proteomic approach to dynamically study the mechanism of pollen-pistil interactions during jasmine crossing.

Jasmine (Jasminum sambac Aiton, Oleaceae) flowers are widely consumed in many countries for their tea-making, medicinal and ornamental properties. To improve the quality and yield of flowers, it is very important to carry out cross-breeding between different petal types of jasmine. However, because of the difficulty of sexual reproduction, there is no report on the success of jasmine crosses. In this paper, single- and double-petal jasmine plants were crossed artificially. The stigmas of single-petal plants post pollination, including those at 0 h after pollination (CK), 1 h after pollination (T1) and 6 h after pollination (T2), were sequenced by transcriptomic combined with proteomic analyses. A total of 178,098 gene products were assembled. Simultaneously, a total of 2337 protein species were identified. Some regulatory gene products and functional protein species were identified that may be involved in the process of pollen-pistil interactions. These findings suggest that the identified differentially expressed gene products and differentially accumulated protein species may play vital roles in jasmine plants in response to pollen-pistil interactions, providing important genetic resources for further functional dissection of the molecular mechanisms of these interactions. SIGNIFICANCE: These results have important scientific significance to take effective measures to overcome pre-fertilization barriers and to guide the cross breeding of jasmine. Further, they can also be used for reference in other plant breeding with the same fertilization barriers.

A 12-hour rapid titration method for cancer pain: a randomized, controlled, open-label study.

BACKGROUND: Opioid titration is the best way to achieve a balance of pain relief and tolerable side effects for moderate-to-severe cancer pain. Rapid dose titration helps to achieve early analgesia. We explored the efficacy and safety of a 12-hour rapid dose titration in treating cancer pain. METHODS: Opioid-naïve patients with moderate-to-severe cancer pain were randomly divided into oxycodone group and morphine group. The medicines were adjusted to oxycodone sustained-release tablets after 12 hours, and the dose of oxycodone sustained-release tablets was adjusted every 12 hours. The analgesic efficacy and adverse reactions during the treatment were observed until the 72nd hour. RESULTS: A total of 106 patients were included in the analysis, with 51 patients in the oxycodone group and 55 in the morphine group. The pain control rate of all patients reached 96.2% 24 hours after treatment, and it was not significantly different between two groups (P=0.619). The proportion of Numeric Rating Scale (NRS) score that decreased by ≥50% was significantly higher in the oxycodone group than in the morphine group (P=0.013). In the first 12 hours and 24 hours, significantly lower proportions of patients in the oxycodone group experienced multiple episodes of breakthrough pain (BTP) than in the morphine group (P=0.032, P=0.021, respectively). The quality of life of the patients in the oxycodone group was significantly higher than that in the morphine group at the 24th hour (P=0.047), as was the degree to which the quality of life had improved (P<0.001). Only grade 1 or 2 adverse reactions were observed during the study period, and no significant difference between two groups. CONCLUSIONS: The 12-hour rapid dose titration method can achieve early analgesia, with mild adverse reactions. In particular, the rapid titration method with background sustained-release oxycodone can reduce BTP episodes and achieve significant early pain relief.