Chronic myelomonocytic leukemia presenting as relapsing thrombotic thrombocytopenic purpura.

A 67-year-old woman presented with fever, purpura, and confusion. A preliminary diagnosis of thrombotic thrombocytopenic purpura (TTP) was made on the basis of clinical presentation and lab findings, such as reduced platelet count, increased bilirubin, and so on. She was treated with therapeutic plasma exchange (TPE) and methylprednisolone. During the treatment, peripheral blood monocytosis (monocyte 4 × 10(9)/L) was noticed. The monocytes were CD56 positive. A putative diagnosis of chronic myelomonocytic leukemia (CMML) was proposed. Three months later, the diagnosis of CMML was established on the basis of persistent monocytosis. All other potential causes were considered (e.g., quinine exposure, diarrhea) and excluded. This case highlights the needs to consider hematological malignancy such as CMML in patients with TTP.

Integrative transcriptomic analysis deciphering the role of rice bHLH transcription factor Os04g0301500 in mediating responses to biotic and abiotic stresses.

Understanding the signaling pathways activated in response to these combined stresses and their crosstalk is crucial to breeding crop varieties with dual or multiple tolerances. However, most studies to date have predominantly focused on individual stress factors, leaving a significant gap in understanding plant responses to combined biotic and abiotic stresses. The bHLH family plays a multifaceted regulatory role in plant response to both abiotic and biotic stresses. In order to comprehensively identify and analyze the bHLH gene family in rice, we identified putative OsbHLHs by multi-step homolog search, and phylogenic analysis, molecular weights, isoelectric points, conserved domain screening were processed using MEGAX version 10.2.6. Following, integrative transcriptome analysis using 6 RNA-seq data including Xoo infection, heat, and cold stress was processed. The results showed that 106 OsbHLHs were identified and clustered into 17 clades. Os04g0301500 and Os04g0489600 are potential negative regulators of Xoo resistance in rice. In addition, Os04g0301500 was involved in non-freezing temperatures (around 4°C) but not to 10°C cold stresses, suggesting a complex interplay with temperature signaling pathways. The study concludes that Os04g0301500 may play a crucial role in integrating biotic and abiotic stress responses in rice, potentially serving as a key regulator of plant resilience under changing environmental conditions, which could be important for further multiple stresses enhancement and molecular breeding through genetic engineering in rice.

Clinicopathologic variables predicting tumor response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND AND OBJECTIVES: To identify clinicopathologic variables that could predict pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: The study enrolled 108 patients who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and December 2010. Tumor responses to neoadjuvant chemotherapy were assessed in terms of tumor regression. Statistical analyses were performed to identify factors associated with pathologic tumor response. RESULTS: Tumor regression was found in 22.2% (24/108) patients, patients with tumor regression observed better overall survival as compared to that of patients without tumor regression. Univariate and multivariate analyses observed that both tumor differentiation and tumor size were independent predictors of tumor regression. CONCLUSIONS: This study suggests that both tumor differentiation and tumor size is the most important clinical predicator of pathologic tumor response, it may be of benefit in the selection of treatment options in locally advanced gastric cancer.

Drug Release from Gelsolin-Targeted Phase-Transition Nanoparticles Triggered by Low-Intensity Focused Ultrasound.

PURPOSE: Current strategies for tumour-induced sentinel lymph node detection and metastasis therapy have limitations. It is essential to identify and provide warnings earlier for tumour metastasis to carry out effective clinical interventions. In addition, traditional cancer chemotherapy encounters drastic limitations due to the nonspecific delivery of antitumour drugs and severe side effects. We aimed to exploit the potential of gelsolin (GSN) monoclonal antibody as a targeting agent and perfluorohexane (PFH) as a phase-transition agent to maximize the cytotoxic effect of poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug controllable release systems for Hca-F cells. METHODS: We co-encapsulated PFH and doxorubicin (DOX) into PLGA nanoparticles (NPs) and further conjugated GSN monoclonal antibody onto the surface of NPs to form GSN-targeted phase transition polymer NPs (GSN-PLGA-PFH-DOX) for both imaging and therapy of tumours and metastatic lymph nodes. To promote and trigger drug release on demand, low-intensity focused ultrasound (LIFU) was applied to achieve a controllable release of the encapsulated drug. RESULTS: GSN-PLGA-PFH-DOX NPs exhibited characteristics such as a narrow size distribution and smooth surface. GSN-PLGA-PFH-DOX NPs could also specifically bind to Hca-F cells and increase the ultrasound contrast agent (UCA) image contrast intensity. GSN-PLGA-PFH-DOX NPs enable GSN-mediated targeting and biotherapeutic effects as well as LIFU-responsive drug release, resulting in synergistic cytotoxic effects in GSN-overexpressing cells in vitro. CONCLUSION: Our work might provide a strategy for the imaging and chemotherapy of primary tumours and their metastases.

Combined diagnosis of ultrasonic elastography and BI-RADS classification increases diagnostic value in female patients with breast neoplasms.

OBJECTIVE: This study was designed to investigate the clinical value of ultrasonic elastography combined with the Breast Imaging Reporting and Data System (BI-RADS) classification in patients with breast neoplasms. METHODS: A retrospective observational study was conducted on 89 patients with breast neoplasms hospitalized from June 2017 to June 2018. All the enrolled patients had received ultrasound examinations. The diagnostic value of ultrasonic elastography, BI-RADS classification, and the combined diagnosis for breast neoplasms was analyzed. RESULTS: The postoperative pathological examination showed 51 cases of benign lesions and 38 cases of malignant lesions among the 89 cases. The detection of the focal zone revealed 75 benign and 44 malignant lesions. Ultrasonic elastography misdiagnosed 8 malignant lesions as benign and 17 benign lesions as malignant; BI-RADS classification misdiagnosed 7 malignant lesions as benign and 15 benign lesions as malignant; The combined diagnosis misdiagnosed 2 malignant lesions as benign and 4 benign lesions as malignant. The sensitivity of the combined diagnosis was higher than that of ultrasonic elastography (P<0.05). The specificity and positive- and negative predictive values of the combined diagnosis were all higher than those of ultrasonic elastography and BI-RADS classification (all P<0.05). CONCLUSION: Ultrasonic elastography combined with BI-RADS classification has high clinical application value in the diagnosis of breast neoplasms, especially the sensitivity to benign and malignant lesions. And compared with the mono-detection of either ultrasonic elastography or BI-RADS classification, the combined detection yields significantly higher diagnostic accuracy.

High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study.

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.

Identification of microalgae cultured in Bold's Basal medium from freshwater samples, from a high-rise city.

This study aimed at exploring microalgal heterogeneity from fresh water samples collected from inland water bodies in the heavily built city of Singapore. Culturable pure isolates (n = 94) were subject to an in-house microalgal DNA extraction method and LSU rDNA sequencing. Isolates were analysed for their predominance and distribution. A total of 17 different algal genera were identified (H = 2.8, EH = 0.6), of which Scenedesmus spp. and Chlorella spp. constituted 27.5% and 21.3% of isolates respectively, followed by Micractinium spp. (18.8%) and Chlamydomonas spp. (12.5%). We also report 16 new microalgal strains from this region. The data is important from an ecological and biotechnological perspective.

Estrogen receptor alpha variant ERalpha46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17beta-oestradiol.

BACKGROUND: Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors alpha and beta (ERalpha, ERbeta). The recently identified ERalpha46 resulted from exon 1-deletion from the 66-kDa full length form of ERalpha66 is devoid of the transactivation domain AF-1, whose function remains largely unknown. METHODS: In this study, we compared the expression of ERalpha46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction (PCR). Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERalpha46, was transfected with ERalpha46-expression vector; methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17beta-oestradiol. RESULTS: Higher ERalpha46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERalpha46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G(0/1) phase and a reduced proportion of cells in G(2)/M phase after exposed to 10(-8) mol/L 17beta-oestradiol. There were also more positive TUNEL stained cells in ERalpha46-transfected cells than the control cells in the presence of 17beta-oestradiol (P < 0.05). CONCLUSIONS: These data suggest that ERalpha46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17beta-oestradiol.

New utility of an old marker: serum low-density lipoprotein predicts histopathological response of neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. PATIENTS AND METHODS: A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker's tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. RESULTS: Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. CONCLUSION: In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice.

Targeting Notch1 and proteasome as an effective strategy to suppress T-cell lymphoproliferative neoplasms.

The T-cell lymphoproliferative neoplasms (T-LPN) are characterized by a poor clinical outcome. Current therapeutics are mostly non-selective and may induce harmful side effects. It has been reported that NOTCH1 activation mutations frequently associate T-LPN. Because anti-Notch1 based therapies such as γ-secretase inhibitors (GSI) are less efficient and induce considerable side effects, we hypothesized that combining low concentrations of GSI and the proteasome inhibitor bortezomib (BTZ) may provide an effective and tolerable approach to treat T-LPN. Hence, we analyzed the in vitro and in vivo effects of GSI-I and BTZ, alone or in combination, against T-LPN. GSI-I and BTZ synergistically decreased cell viability, proliferation, and colony formation, and induced apoptosis in T-LPN cell lines. Furthermore, combining GSI-I and BTZ decreased the viability of primary T-LPN cells from patients. These effects were accompanied by deregulation of Notch1, AKT, ERK, JNK, p38 MAPK, and NF-κB survival pathways. Moreover, combination treatment inhibited T-LPN tumor growth in nude mice. In all experiments, combining low concentrations of GSI-I and BTZ was superior to using a single agent. Our data support that a synergistic antitumor activity exists between GSI-I and BTZ, and provide a rationale for successful utilization of dual Notch1 and proteasome inhibition to treat T-LPN.

The relationship between Lin28 and the chemotherapy response of gastric cancer.

OBJECTIVE: The aim of the study reported here was to identify whether a stem cell biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: The study enrolled 47 patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue was biopsied by gastroscopy and Lin28 expression in the tissue was measured by immunohistochemistry. Statistical analyses were performed to identify the relationship between Lin28 expression and tumor regression grade. RESULTS: Of the 47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic response in 18 (38.3%). Receiver-operating characteristic curve analysis showed that the histoscore of Lin28 expression with 0.325 as a cutoff value could differentiate between pathologic response and nonresponse. Multivariable analysis showed that Lin28 expression was an independent predictive factor for pathologic response to neoadjuvant chemotherapy (P = 0.006). CONCLUSION: Lin28 expression was associated with pathologic tumor response in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can serve as a predictive biomarker for neoadjuvant chemotherapy in patients with gastric cancer.

Combination therapy with arsenic trioxide, all-trans retinoic acid, and chemotherapy in acute promyelocytic leukemia patients with various relapse risks.

To improve the recovery rate of high-risk patients with acute promyelocytic leukemia (APL), we used all-trans retinoic acid (ATRA)/arsenic trioxide (ATO)/daunorubicin combination in remission induction, daunorubicin and cytarabine in consolidation, and ATRA/ATO/methotrexate ± 6-mercaptopurine in maintenance treatment of APL patients with various risks for relapse. Our results showed a high complete remission rate of 95.3%. Excluding the cases of early-death, no significant differences in event-free survival were observed between the intermediate-risk and high-risk group (p = 0.393) and the low-risk and high-risk group (p = 0.162). In addition, there were no significant differences between the groups in cumulative incidence of central nervous system relapse. In conclusion, our results suggest that APL patients benefit from combination ATO/ATRA/chemotherapy, and that this regimen is especially beneficial for patients with high-risk prognostic factors.

Tirucallane-type triterpenoid saponins from the roots of Sapindus mukorossi.

Six new tirucallane-type triterpenoid saponins, sapimukosides E-J (1-6) were isolated from the roots of Sapindus mukorossi GAERTN. Their structures were elucidated by a combination of spectral and chemical analysis.

NMR assignments and single-crystal X-ray diffraction analysis of deoxyloganic acid.

7-Deoxyloganic acid (1), citrusin C (2), 3,4-dihydroxyl benzoic acid (3) and (E)-caffeic acid (4) were isolated from the water-soluble fraction of ethanol extracts of Morina nepalensis var. alba Hand.-Mazz. and their structures were determined on the basis of spectroscopic evidence. The total assignments of 1H and 13C NMR spectra of 1 in solvents CD3OD, D2O and CDCl3 were reported, in addition to the single-crystal X-ray diffraction analysis of its tetraacetate 1a. All compounds were obtained from Morina genus for the first time.

New tirucallane-type triterpenoid saponins from Sapindus mukorossi Gaetn.

Two new tirucallane-type triterpenoid saponins, sapimukoside C (1) and sapimukoside D (2), have been isolated from the roots of Sapindus mukorossi Gaetn. Their structures have been determined, on the basis of spectral and chemical analysis, as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L- arabinopyranosyl-(1-->3)]-beta-D-glucopyranosyl (21,23R)-epoxyl tirucalla-7,24-diene-(21S)-ethoxyl-3 beta-ol (1) and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1-->3)]- beta-D-glucopyranosyl (21,23R)-epoxyl tirucall-7,24-diene-(21S)-methoxyl-3 beta-ol (2).

Isolation and characterization of Brachystemidines A-E, novel alkaloids from Brachystemma calycinum.

Five novel alkaloids, brachystemidines A-E (1-5), were isolated from the roots of Brachystemma calycinum. Their structures were established by spectral data, especially by 1D and 2D NMR techniques. The crystal structure of brachystemidine D was determined via X-ray diffraction analysis.

Four new oleanane type saponins from Morina nepalensis var. alba.

Four new oleanane type saponins, monepalosides G-J (1-4), were isolated from the water-soluble part of the whole plant of Morina nepalensis var. alba Hand-Mazz. On the basis of chemical and spectroscopic evidence, their structures were determined as 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-alpha-L-arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside G, 1), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-beta-D-xylopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside H, 2), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[beta-D-glucopyranosyl-(1 --> 2)]-alpha-L-arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside I, 3), 3-O-beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 3)]-alpha-L-arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside J, 4), respectively. Two-dimensional NMR spectra, including H-H COSY, HMQC, 2D HMQC-TOCSY, HMBC and ROESY were utilized in the structure elucidation and complete assignments of 1H and 13C NMR spectra.