Publications by authors named "Na Cui"

120 Publications

Enhancement of Lipid Productivity and Self-flocculation by Cocultivating Monoraphidium sp. FXY-10 and Heveochlorella sp. Yu Under Mixotrophic Mode.

Appl Biochem Biotechnol 2021 Jun 5. Epub 2021 Jun 5.

Faculty of Life Sciences and Technology, Kunming University of Science and Technology, Kunming, 650500, China.

To maintain high microalgae lipid productivity and flocculation efficiency simultaneously and reduce the production cost of microalgae lipids, Monoraphidium sp. FXY-10 with high lipid-producing capacity and Heveochlorella sp. Yu with strong self-flocculation ability were cocultivated and studied. Cocultivated microalgae lipid productivity and flocculation efficiency were increased to 203.8 mg L day and 70.55%, respectively, which is potentially related to the excessive competitive depletion of nitrogen sources and the upregulation of correlative key genes in lipid anabolic metabolism. Under cocultivation conditions, microalgae cells could enter the stationary phase 2 days earlier than that under monocultivation conditions, thus reducing the culture time. Relative expression of the accD, ME, and rbcL genes was upregulated to varying degrees, and the enzyme activities of ACCase, ME, and RuBisCO were also significantly increased compared with those in monocultivation. Moreover, fatty acid composition showed that microalgae lipids in cocultivation exhibited potential as a feedstock for biodiesel.
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http://dx.doi.org/10.1007/s12010-021-03593-xDOI Listing
June 2021

Impact of mTOR signaling pathway on CD8+ T cell immunity through Eomesodermin in response to invasive candidiasis.

J Microbiol Immunol Infect 2021 Apr 20. Epub 2021 Apr 20.

Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China; Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Background: We investigated the effect of the mammalian target of rapamycin (mTOR) pathway on CD8+ T cell immunity through Eomesodermin (Eomes) in intensive care unit (ICU) patients with invasive candidiasis (IC) and in a mouse model.

Methods: We evaluated quantitative changes in parameters of the mTOR/phosphorylated ribosomal S6 kinase (pS6K) pathway and immune system at the onset of infection in ICU patients. The study was registered on 28 February 2017 at chictr.org.cn (ChiCTR-ROC-17010750). We also used a mouse model of Candida infection and constructed T-cell-specific mTOR and T-cell-specific tuberous sclerosis complex (TSC) 1 conditional knockout mice to elucidate the molecular mechanisms.

Results: We enrolled 88 patients, including 8 with IC. The IC group had lower CD8+ T cell counts, higher serum levels of mTOR, pS6K, Eomes and interleukin (IL)-6. The mouse model with IC showed results consistent in the clinical study. The CD8+ T cell immune response to IC seemed to be weakened in TSC1 knockout mice compared with wild-type IC mice, demonstrating that mTOR activation resulted in the impaired CD8+ T cell immunity in IC.

Conclusions: In IC, the mTOR activation may play a vital role in impaired CD8+ T cell immunity through enhancing expression of Eomes. The study was registered on 28 February 2017 at chictr.org.cn (identifier ChiCTR-ROC-17010750).
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http://dx.doi.org/10.1016/j.jmii.2021.03.021DOI Listing
April 2021

Effects of multicycle gonadotropin-releasing hormone antagonist protocols on oxidative stress of follicular fluid and ovarian granulosa cells.

Hum Cell 2021 May 8. Epub 2021 May 8.

Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

The effect of repeated multicycle gonadotropin-releasing hormone antagonist (GnRH-ant) protocols on oxidative stress (OS) in follicular fluid (FF) and ovarian granulosa cells (GCs) remains unclear. This study investigated the effects of repeated multicycle GnRH-ant protocols on OS markers of FF and ovarian GCs. A total of 145 patients were enrolled and divided into four groups: 1 cycle group (n = 42), 2 cycles group (n = 37), 3 cycles group (n = 45), and 4-5 cycles group (n = 21). The FF and ovarian GCs of the patients were collected on the day of last oocyte retrieval and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were tested by ELISA. The results showed that the serum estradiol levels on hCG injection day in the 3 and 4-5 cycles were significantly (P < 0.05) lower than in the 1 and 2 cycles. The number of retrieved oocytes (12.1 ± 3.3 in cycle 1, 11.7 ± 3.1 in cycle 2, 10.4 ± 2.4 in cycle 3, and 9.4 ± 2.4 in cycles 4-5), embryos with two pronuclei (7.6 ± 3.0 in cycle 1, 7.0 ± 2.5 in cycle 2, 6.2 ± 2.6 in cycle 3, and 5.5 ± 2.1 in cycles 4-5), and the rates of high-quality embryos (52.2% in cycle 1, 47.9% in cycle 2, 38.6% in cycle 3, and 36.5% in cycles 4-5), implantation (35.4% in cycle 1, 32.4% in cycle 2, 23.8% in cycle 3, and 22.9% in cycles 4-5) and clinical pregnancy (50.0% in cycle 1, 43.2% in cycle 2, 33.3% in cycle 3, and 23.8% in cycles 4-5) in cycles 3 and 4-5 were significantly (P < 0.05) lower than those in cycles 1 and 2. Compared with 1 and 2 cycles, the 8-OHdG and SOD were significantly increased in the 3-5 cycles, while the CAT and GSH-Px levels were significantly decreased. Together, this study reveals repeated COS with the use of GnRH-ant protocols results in OS and changes the follicle microenvironment of FF and GCs, possibly leading to poor IVF outcomes in patients with 3-5 cycles of COS.
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http://dx.doi.org/10.1007/s13577-021-00545-9DOI Listing
May 2021

Nucleotide-Binding Leucine-Rich Repeat Genes and Are Positive Modulators in the Defense Response to .

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China.

Cucumber powdery mildew caused by is a leaf disease that seriously affects cucumber's yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes and , which participated in regulating the resistance of cucumber to . The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of and were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (HO). The expression analysis showed that the transcript levels of and were correlated with plant defense response against . Moreover, the silencing of and impaired host resistance to , but and overexpression improved resistance to in cucumber. These results showed that and genes positively contributed to the resistance of cucumber to . At the same time, and genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to .
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http://dx.doi.org/10.3390/ijms22083986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069588PMC
April 2021

Nitrate and nitrite as mixed source of nitrogen for Chlorella vulgaris: Growth, nitrogen uptake and pigment contents.

Bioresour Technol 2021 Jun 15;330:124995. Epub 2021 Mar 15.

LGPM, CentraleSupélec, Université Paris-Saclay, SFR Condorcet FR CNRS 3417, Centre Européen de Biotechnologie et de Bioéconomie (CEBB), 3 rue des Rouges Terres, 51110 Pomacle, France.

Chlorella vulgaris was grown using mixed sources of nitrogen (nitrate and nitrite). Starting from B3N as basal medium, nitrate was substituted by nitrite keeping total nitrogen constant over 7 conditions: 0, 20, 40, 50, 60, 80 and 100% NO. Growth rate, nitrogen uptake, photosynthetic apparatus status and pigment contents were monitored. Nitrite addition triggered a growth rate inhibition from early introduction (20% NO, 81 mgNO/l). Nitrate uptake rate increased with nitrate content in the culture medium (maximum at 5.87 mg/l/d, 100% NO), while nitrite uptake remained constant around 2.93 mg/l/d. Photosynthetic apparatus was not impacted by the nitrogen source substitution. Pigments profiles (chlorophyll a, b and total carotenoids) were not statistically different for all the tested conditions. From a biotechnological perspective, this finding rules out the use of nitrite substitution as a pigment manipulating stress strategy.
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http://dx.doi.org/10.1016/j.biortech.2021.124995DOI Listing
June 2021

Effect of Nurse-Led Goal-Directed Lung Physical Therapy on the Prognosis of Pneumonia in Sepsis Patients in the ICU: A Prospective Cohort Study.

J Intensive Care Med 2021 Jan 29:885066620987200. Epub 2021 Jan 29.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.

Background: Pneumonia poses a significant burden on healthcare systems. However, few studies have focused on nurse-led goal-directed lung physical therapy (GDLPT) for pneumonia in sepsis patients in the intensive care unit (ICU).

Objectives: This study aimed to investigate the effects of nurse-led GDLPT on the prognosis of pneumonia in sepsis patients in the ICU.

Methods: We performed a prospective 2-phase (before-and-after) study over 3 years. After an observational phase (phase 1, = 188), we designed, implemented, and evaluated a nurse-led GDLPT protocol (phase 2, = 359) for pneumonia in sepsis patients in the ICU. The primary outcome was 28-day mortality.

Results: We evaluated 742 critically ill patients with sepsis from January 2017 to January 2020. Among the 742 sepsis patients, 609 were diagnosed with pneumonia and 547 who met the inclusion criteria were enrolled in the study. Compared with patients in phase 1, patients in phase 2 had significantly shorter mechanical ventilation duration (5 [4, 6] days vs. 5 [4, 8] days, = 0.037), shorter ICU stay (9 [4, 16] days vs. 9 [6, 20] days, = 0.010), lower ICU mortality (15.0% [54/359] vs. 25.5% [48/188], = 0.003), and lower 28-day mortality (16.7% [60/359] vs. 27.1% ([51/188], = 0.004). Multivariate logistic regression analysis revealed that nurse-led GDLPT (odds ratio 0.540, 95% confidence interval 0.345-0.846, = 0.007), clinical pulmonary infection score (odds ratio 1.111, 95% confidence interval 1.012-1.221, = 0.028), and ventilation day (OR 1.160, 95% CI, 1.058-1.240, <0.001)were independent predictors of 28-day mortality for pneumonia in sepsis patients, and that nurse-led GDLPT was a protective factor.

Conclusions: Nurse-led GDLPT improved the outcomes of pneumonia in sepsis patients, and was particularly associated with shortened mechanical ventilation duration and ICU stay, and reduced ICU mortality and 28-day mortality.
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http://dx.doi.org/10.1177/0885066620987200DOI Listing
January 2021

Lymphocyte and NK Cell Counts Can Predict Sepsis-Associated Delirium in Elderly Patients.

Front Aging Neurosci 2020 11;12:621298. Epub 2021 Jan 11.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

: Sepsis-associated delirium (SAD) is prevalent in elderly patients and is recognized as brain dysfunction associated with increased inflammatory response in the central nervous system during sepsis. Neuroinflammation was demonstrated to be part of its mechanism and we aimed to validate the role of immunity imbalance in a combined retrospective and prospective cohort study. : We performed a retrospective study analyzing the association between SAD and lymphocyte counts in the peripheral blood, alongside a prospective trial evaluating the quantitative changes in lymphocyte subsets and their predictive value for early diagnosis of SAD. : In the retrospective study, among 1,010 enrolled adult patients (age ≥65 years), 297 patients were diagnosed with delirium during intensive care unit (ICU) stay and lymphocyte counts at ICU admission in the SAD group were significantly higher than in non-delirious counterparts (1.09 ± 0.32 vs. 0.82 ± 0.24, respectively, = 0.001). In the prospective study, lymphocyte counts [0.83 (0.56, 1.15) vs. 0.72 (0.40, 1.06) × 10/L, = 0.020] and natural killer (NK) cell counts [96 (68, 118) vs. 56 (26, 92) cells/μl, = 0.024] were significantly higher in the SAD group. The area under the curve value of NK cell count was 0.895 [95% confidence interval (CI): 0.857, 0.933] and of lymphocyte count was 0.728 (95% CI: 0.662, 0.795). An NK cell count cut-off value of 87 cells/ml in septic patients at ICU admission was predictive of delirium with a sensitivity of 80.2% and specificity of 80.8%. : We found that lymphocyte and NK cell counts were significantly higher in senior patients with SAD and that NK cell count may be valuable for the prediction of SAD within elderly patient cohorts.
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http://dx.doi.org/10.3389/fnagi.2020.621298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829191PMC
January 2021

Expressions of ZNF436, β-catenin, EGFR, and CMTM5 in breast cancer and their clinical significances.

Eur J Histochem 2021 Jan 20;65(1). Epub 2021 Jan 20.

Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei.

As the leading malignancy among women, breast cancer is a serious threat to the life and health of women. In this context, it is of particular importance that a proper therapeutic target be identified for breast cancer treatment. We collected the pathological tissues of 80 patients, with the view to discovering appropriate molecular targets for the treatment of breast cancer, this paper analyzes the expressions of ZNF436, β-catenin, EGFR and CMTM5 in breast cancer tissues, as well as their correlations with breast cancer in combination with the clinicopathologic characteristics of studied patients. Immunohistochemistry (IHC) was utilized to detect the expression levels of ZNF436, β-catenin, EGFR and CMTM5 in cancerous and paracancerous tissues of breast cancer patients. The expression levels of ZNF436, β-Catenin and EGFR in breast cancer tissues were significantly greater than those in paracancerous tissues in this study (p<0.05), while CMTM5 was highly expressed in paracancerous tissues (p<0.05). Additionally, the correlation of the expressions of such indicators with the staging, differentiation and lymphatic metastasis of breast cancer, were also found to be statistically significant at the level p<0.05. The different expression levels of ZNF436, β-catenin, EGFR and CMTM5 in breast cancer and paracancerous tissues open up the possibility of utilizing them as molecular markers for breast cancer. These findings provide a theoretical basis for targeted molecular therapies for breast cancer, and hence carry a significant practical significance.
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http://dx.doi.org/10.4081/ejh.2021.3173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856825PMC
January 2021

[Metagenomic Analysis Provides Insights into Bacterial Communities, Antibiotic Resistomes, and Public Health Risks in the Dongping Lake Reservoir].

Huan Jing Ke Xue 2021 Jan;42(1):211-220

College of Biological Science and Engineering, Hebei University of Economics and Business, Shijiazhuang 050061, China.

Owing to the long residence times of water, water reservoirs readily contribute to the accumulation of antibiotic resistant gene (ARG). It is of great public health significance to explore bacterial communities, antibiotic resistomes, and the potential public health risks of water reservoirs. In this study, metagenomic sequencing was used to analyze and compare the bacterial communities, ARG profiles, ARG-horizontal transfer, and ARG-carrying pathogens in the water and sediments of the Dongping Lake Reservoir in the dry and the wet seasons. Compared with that of the sediments, the results showed that both the bacterial communities and ARG profiles in the water were significantly influenced by the seasons, and the total ARG abundance in the dry season was significantly higher than that in the wet season. The total ARG abundance in the sediments was higher than that in water, but the horizontal transfer potential of ARG in the water was higher than that in the sediment. A total of 377 ARG subtypes belonging to 20 ARG types were found in this study. Bacitracin and vancomycin resistance genes were the main ARG types in the water and sediments, respectively, and Proteobacteria and Actinobacteria were the major ARG-carrying bacteria in the water and sediments, respectively. In addition, 30 clinical pathogens carrying ARGs were identified, including , , , and More importantly, two concurrently carried virulence factor and ARG. In summary, this study revealed that a variety of ARG types existed in the Dongping Lake Reservoir, which has posed potential public health risks by contributing to the horizontal transfer of ARG and the accumulation of clinical pathogens. Therefore, it is necessary to regularly monitor the bacterial community and ARG profile in various water bodies.
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http://dx.doi.org/10.13227/j.hjkx.202005305DOI Listing
January 2021

Effect of nurse-led, goal-directed lung physiotherapy on prognosis of patients with sepsis caused by Acinetobacter baumannii pulmonary infection.

Int J Infect Dis 2021 Feb 2;103:167-172. Epub 2020 Dec 2.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China; Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China. Electronic address:

Objectives: To investigate the role of nurse-led, goal-directed lung physiotherapy on the prognosis of patients with sepsis caused by Acinetobacter baumannii pulmonary infection.

Methods: Patients with sepsis caused by A. baumannii pulmonary infection were recruited and divided into a control group (phase 1) and a treatment group (phase 2). Both groups received standard therapy for sepsis, and patients in phase 2 also received nurse-led, goal-directed lung physiotherapy. The primary outcome measure was 28-day mortality.

Results: Among 742 patients with sepsis, 201 were diagnosed with A. baumannii pulmonary infection. Compared with patients in phase 1, patients in phase 2 had a significantly shorter duration of mechanical ventilation {median 4 (interquartile range (IQR) 3-5] vs 5 (IQR 3-12) days; P = 0.004}, lower intensive care unit (ICU) mortality [13.6% (18/132) vs 27.5% (19/69); P = 0.016] and lower 28-day mortality [21.2% (28/132) vs 37.7% (26/69); P = 0.012]. As a protective factor, nurse-led, goal-directed lung physiotherapy (odds ratio 0.341, 95% confidence interval 0.155-0.751; P = 0.008) was an independent risk factor for 28-day mortality.

Conclusions: Nurse-led, goal-directed lung physiotherapy shortened the duration of mechanical ventilation and ICU stay, and decreased ICU mortality and 28-day mortality in patients with sepsis caused by A. baumannii pulmonary infection.
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http://dx.doi.org/10.1016/j.ijid.2020.11.196DOI Listing
February 2021

Realgar increases defenses against infection by Enterococcus faecalis in Caenorhabditis elegans.

J Ethnopharmacol 2021 Mar 4;268:113559. Epub 2020 Nov 4.

School of Pharmacy, Lanzhou University, Lanzhou, PR China. Electronic address:

Ethnopharmacological Relevance: Realgar has been used in traditional remedies for a long history in China and India. It is clinically used to treat diverse cancers, especially acute promyelocytic leukemia (APL), chronic myelogenous leukemia (CML) in China. However, paradoxic roles of realgar to increase or decrease immunity are reported. It is urgent to address this question, due to immune depression can be strongly benefit to cancer development, but detrimental to patients.

Aim Of The Study: This present work is to explore whether realgar promote or suppress immune responses, and shed light on its mode of action. Our results should provide cues for rational strategy to explore realgar for clinical use.

Material And Methods: Infection model in vivo was established by using Enterococcus faecalis to attack Caenorhabditis elegans, then realgar was used to treat the infected worms to investigate its effects on infectivity and the underlying mechanism. Killing analysis was carried out to test whether realgar can mitigate worm infection. Thermotolerance resistance analysis was used to evaluate if realgar functions hormetic effect. Quantification of live E. faecalis in nematode intestine was employed to ascertain if realgar alleviate the bacterial load in worm gut. Quantitative real-time PCR (qRT-PCR) was used to test the expression of antibacterial effectors. Western blot was used to test the effect of realgar on the expressions of p38 and phospho-p38 in worms infected by E. faecalis.

Results: Realgar alleviated the infected worms in strains of N2, glp-4, and daf-2, but failed in sek-1, glp-4; sek-1, and daf-2; daf-16 when p38 MAPK or daf-16 was blocked or inactivated. Western blot assay demonstrated that realgar increased the expression of phosph-p38. Thermotolerance assay showed that realgar played a hormetic role on nemtodes, triggered protective response and reduced bacterial load after realgar treatment for 120 h qRT-PCR demonstrated that realgar significantly increased antibacterial effectors, thus leading to pathogen elimination.

Conclusion: Realgar increased defenses against E. faecalis in C. elegans by inducing both immune responses and protective responses. It was regulated by p38 MAPK pathway and DAF-16.
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http://dx.doi.org/10.1016/j.jep.2020.113559DOI Listing
March 2021

Evaluation of the updated " score" with Sepsis 3.0 criteria in critically ill patients.

Ann Transl Med 2020 Aug;8(15):917

Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Background: The score proposed in 2009 was calculated on the definition of "severe sepsis", which was removed in the Sepsis 3.0 definition. This study investigated the clinical relevance of score with the updated Sepsis 3.0 definition (CS-3.0) instead of severe sepsis (CS-2009) in the new admitted critically ill patients.

Methods: We performed a retrospective analysis on a single center public database. All patients with ICU stay ≥72 hours were included in this study. The score was calculated based on the data collected on ICU admission. The incidence of invasive candidiasis was determined and its relationship with the CS-2009 and CS-3.0 was studied.

Results: A total of 17,666 patients were identified after screening 58,976 hospital admissions, and 436 cases (2.5%) were diagnosed with invasive candidiasis. In the infection group, the number of patients who met the Sepsis 3.0 criteria was greater than the number of patients with severe sepsis (81.2% 78.4%, P<0.005). The area under curve of the CS-2009 was 0.789 (95% CI: 0.765-0.813) and the CS-3.0 was 0.804 (95% CI: 0.782-0.827).

Conclusions: Our study confirmed the clinical relevance and comparative superiority of the updated score model, using the Sepsis 3.0 definition, compared with the classic sepsis/severe sepsis model, in assessment of critically ill patients. Considering the clinical importance of organ dysfunction in ICI, the Sepsis 3.0 should be used as the basis for prediction of invasive candidiasis.
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http://dx.doi.org/10.21037/atm-20-995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475415PMC
August 2020

Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.

Crit Care 2020 09 11;24(1):554. Epub 2020 Sep 11.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, China.

Background: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018.

Methods: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database.

Results: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality.

Conclusions: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.
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http://dx.doi.org/10.1186/s13054-020-03270-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484920PMC
September 2020

Association between Body Mass Index and Reproductive Outcome in Women with Polycystic Ovary Syndrome Receiving IVF/ICSI-ET.

Biomed Res Int 2020 21;2020:6434080. Epub 2020 Aug 21.

Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China.

Objective: To examine the association between body mass index (BMI) and the outcome of in vitro fertilization or intracytoplasmic sperm injection embryo transfer- (IVF/ICSI-ET) assisted reproduction in women with polycystic ovary syndrome (PCOS) receiving the ultra-long agonist protocol.

Methods: We retrospectively identified all women receiving IVF/ICSI-ET for the first time using the ultra-long protocol between January 2013 and January 2018 at our hospital. Only women at ≤35 years of age receiving the first cycle were analyzed.

Results: A total of 1782 women were included in the analysis: 42 were underweight, 742 were overweight, 198 were obese, and 800 were normal weight. Gonadotropin dosage and duration were comparable between underweight and normal weight groups but were significantly higher/longer in overweight and obese groups ( < 0.008). The number of oocytes retrieved was significantly lower in overweight and obese groups than in the normal weight group ( < 0.008). The number of transferable embryos was significantly higher in normal weight group than overweight and obese groups ( < 0.008). Embryo implantation rate, clinical pregnancy rate, full-term birth rate, and live birth rate did not differ among the 4 groups. The cycle cancellation rate was lower in the overweight and obese group than normal weight group ( < 0.008). The miscarriage rate was higher in the obese group than the normal weight group ( < 0.008). In multivariate logistic regression analysis, abnormal BMI was an independent risk for miscarriage (OR: 1.069, 95% CI 1.020, 1.122; = 0.006).

Conclusion: Overweight and obesity are associated with poor outcomes in PCOS patients receiving ultra-long protocol. Measures to reduce body weight should be encouraged in overweight and obese PCOS women at ≤35 years of age prior to assisted reproductive technology (ART).
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http://dx.doi.org/10.1155/2020/6434080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463361PMC
April 2021

Effect of increasing oxygen partial pressure on Saccharomyces cerevisiae growth and antioxidant and enzyme productions.

Appl Microbiol Biotechnol 2020 Sep 13;104(18):7815-7826. Epub 2020 Aug 13.

Chair of Biotechnology, LGPM, CentraleSupélec, Université Paris-Saclay, SFR Condorcet FR CNRS 3417, Centre Européen de Biotechnologie et de Bioéconomie (CEBB), 3 rue des Rouges Terres, 51110, Pomacle, France.

This study investigated the impact of oxygen partial pressure on yeast growth. Saccharomyces cerevisiae cells were exposed to various hyperbaric air conditions from 1 bar to 9 bar absolute pressure (A). Batch cultures were grown under continuous airflow in a 750 mL (500 mL culture) bioreactor and monitored through growth rate and specific yields of ethanol and glycerol. In addition, the concentrations of antioxidant metabolites glutathione (reduced state, GSH and oxidized state, GSSG) and the activity of antioxidative enzymes superoxide dismutases (SOD) and catalases (CAT) were monitored. The results demonstrated that the different oxygen partial pressures significantly impacted the key growth parameters monitored. Compared with atmospheric pressure, under 2 to 5 bar (A), yeast cells showed higher growth rates (μ = 0.32 ± 0.01 h) and higher catalase (CAT) concentrations (214 ± 5 mU/g). GSH/GSSG ratio (6.36 ± 0.37) maintained until 6 bar (A) and total SOD (240 ± 5 mU/g) level significantly increased compared with 2 bar (A) until 7 bar (A). Under 6 to 9 bar (A), cell growth was inhibited, and a pressure of 9 bar (A) led to excessive GSSG accumulation (GSH/GSSG = 0.31 ± 0.06). The inhibition of t-SOD (160 ± 3 mU/g) and CAT (62.73 ± 0.2 mU/g) was observed under 9 bar (A). A reference experiment (8 bar (A) N + 1 bar (A) air) confirmed that the observed behaviors were entirely due to O. In addition to their utility in biotechnological process design, these results showed that growth impairment was solely due to oxidative stress induced by excessive oxygen pressure. KEY POINTS: • Yeast cells were grown in batch mode under 1 to 9 bar (A) air pressures and up to 5 bar (A) promoted then hindered growth. • The GSH/GSSG ratio was stable up to 5 bar (A) then GSSG accumulated to excess. • Complementary investigations of the activity of SOD and CAT validated growth limitations due to oxidative stress.
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http://dx.doi.org/10.1007/s00253-020-10824-4DOI Listing
September 2020

Research on the Correlation of Serum PCT and Plasma GSN Levels with the Prognosis of Urosepsis Patients.

Pak J Med Sci 2020 Jul-Aug;36(5):1011-1014

Ning Chen, Department of ICU, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, P. R. China.

Objective: To explore the correlation of procalcitonin (PCT) and gelsolin (GSN) with the prognosis of urosepsis patients.

Method: The data of 71 urosepsis patients from March 2015 to April 2019 who were admitted to and treated in Affiliated Hospital of Hebei University were analyzed and compared with those of 92 healthy persons. Serum PCT and plasma GSN levels at different times after treatment were detected. According to prognosis, patients were classified into the good prognosis group or the poor prognosis group. The serum PCT and plasma GSN levels of both groups were compared.

Result: The serum PCT level of the urosepsis group on the 1, 3, 5 and 7 days was obviously higher than that of the control group (P<0.05). The plasma GSN levels of the urosepsis group on the 1, 3, 5 and 7 days were obviously lower than those of the control group (P<0.05). The serum PCT level of the poor prognosis group on the 1, 3, 5 and 7 days was obviously higher than that of the good prognosis group (P<0.05). The plasma GSN level of the poor prognosis group on the 1, 3, 5 and 7 days was obviously lower than that of the good prognosis group (P<0.05). PCT was an independent risk factor influencing the prognosis of urosepsis patients and that GSN was a protective factor (P<0.05).

Conclusion: The serum PCT and plasma GSN levels can accurately predict the severity and prognosis of urosepsis patients and reflect the disease state of early urosepsis patients. High PCT levels and low GSN levels indicate poor prognosis, and clinicians should consider these values.
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http://dx.doi.org/10.12669/pjms.36.5.2143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372696PMC
July 2020

Green and Durable Lightweight Aggregate Concrete: The Role of Waste and Recycled Materials.

Materials (Basel) 2020 Jul 7;13(13). Epub 2020 Jul 7.

Shandong Provincial Key Laboratory of Preparation and Measurement of Building Materials, School of Materials Science and Engineering, University of Jinan, Jinan 250022, Shandong, China.

Lightweight aggregate concrete manufactured by solid waste or recycled by-products is a burgeoning topic in construction and building materials. It has significant merits in mitigating the negative impact on the environment during the manufacturing of Portland cement and reduces the consumption of natural resources. In this review article, the agricultural and industrial wastes and by-products, which were used as cementitious materials and artificial lightweight aggregate concrete, are summarized. Besides, the mechanical properties, durability, and a few advanced microstructure characterization methods were reviewed as well. This review also provides a look to the future research trends that may help address the challenges or further enhance the environmental benefits of lightweight aggregate concrete manufactured with solid waste and recycled by-products.
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http://dx.doi.org/10.3390/ma13133041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372475PMC
July 2020

Effect of lignin and plant growth-promoting bacteria (Staphylococcus pasteuri) on microbe-plant Co-remediation: A PAHs-DDTs Co-contaminated agricultural greenhouse study.

Chemosphere 2020 Oct 18;256:127079. Epub 2020 May 18.

Key Laboratory of Regional Environment and Eco-remediation, Shenyang University, Shenyang, 110044, China. Electronic address:

Due to the ecological toxicity and environmental residues, how to remove the persistent organic pollutants (POPs), especially of polycyclic-aromatic-hydrocarbons (PAHs) and dichloro-diphenyl-trichloroethanes (DDTs), from agricultural soil has captured the attention of scholars for a long time. To develop an effective and low-cost in situ co-remediation technique, five independent but complementary treatments were used on an over-standard PAHs-DDTs co-contaminated soil in an agricultural greenhouse. Experimental results identified that the combination of microbe (Bacillus methylotrophicus) - plant (Brassica rapa) could remove rhamnolipid activated PAHs and DDTs effectively after enhanced by Staphylococcus pasteuri. Also, the Benzoapyrene and total DDTs residue in Brassica rapa was up to the standard of National (China) food safety. The lignin enhanced the removal of high-rings PAHs and p-p' DDE but reduced soil microbial biomass carbon and soil enzymes activity (polyphenol oxidase, invertase and acid phosphatase). Pearson correlation analysis showed that polyphenol oxidase activity was significantly related to the PAHs/DDTs dissipation rate. Our research suggested a new amendment that could remediate PAHs/DDTs co-contaminated agricultural soil without interrupting crop production, and the polyphenol oxidase activity should be considered as a micro-ecological indicator in this process.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127079DOI Listing
October 2020

T-Bet Expression Mediated by the mTOR Pathway Influences CD4 T Cell Count in Mice With Lethal Sepsis.

Front Microbiol 2020 5;11:835. Epub 2020 May 5.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

The sustained high morbidity and mortality of sepsis are mainly caused by compromise of host immunity. Clinically, it is often manifested as a significant decrease in CD4 T cell count, although the mechanism is unclear. We established a lethal mice sepsis model and used Murine Sepsis Score to group mice with different disease severity to establish the influence of T-bet expression on CD4 T cell count in sepsis. We found that CD4 T cell count decreased in -infected compared to uninfected mice, and the degree of decrease increased with aggravation of sepsis. Expression of T-bet similarly decreased with worsening of sepsis, but it was significantly enhanced in candidiasis in comparison of naïve state. To clarify its possible mechanism, we measured the activity of mammalian target of rapamycin (mTOR), which is a key regulator of T-bet expression. The mTOR pathway was activated after infection and its activity increased with progression of sepsis. We used mice with T-cell-specific knockout of or tuberous sclerosis complex ()1 to further inhibit or strengthen the mTOR signaling pathway. We found that deletion mice had a higher CD4 T cell count by regulating T-bet expression, and the result in deletion mice was reversed. These results demonstrate that T-bet expression mediated by the mTOR pathway influences the CD4 T cell count in mice with sepsis.
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http://dx.doi.org/10.3389/fmicb.2020.00835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214724PMC
May 2020

Lymphocyte subset counts as diagnostic and prognostic markers for carbapenem-resistant Enterobacteriaceae (CRE) infection in critically ill patients.

Int J Infect Dis 2020 Jul 7;96:315-322. Epub 2020 May 7.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China. Electronic address:

Objectives: This study investigated the use of lymphocyte subset counts as diagnostic and prognostic markers for carbapenem-resistant Enterobacteriaceae (CRE) infection.

Methods: We assessed the lymphocyte subset populations and other clinical parameters of septic patients upon intensive care unit (ICU) admission, and evaluated their potential impact on CRE infection diagnosis and outcome.

Results: Among 373 septic patients, 51 were diagnosed with CRE infection. The 28-day mortality was significantly higher in CRE than non-CRE patients (35.3% vs 14.9%). The T lymphocyte count and CD4CD28 T cell count were both independent risk factors for CRE infection, with the latter had the best diagnostic ability (AUC: 0.908; p < 0.0001). Lower CD4CD28 T cell counts were associated with higher likelihoods of CRE infection. The CRE incidence and 28-day mortality of CRE-infected patients could be predicted using cutoff values of 242 (sensitivity: 83.9%; specificity: 87.5%) and 58.5 (sensitivity: 100%; specificity: 61.1%) CD4CD28 T cells/μl at ICU admission, respectively.

Conclusions: Septic patients with CRE infection had higher 28-day mortality. Given that the CD4CD28 T cell count was significantly lower in CRE than non-CRE septic patients and a lower cell count was significantly associated with higher 28-day mortality, CD4CD28 T cell counts may be useful markers for early diagnosis of CRE infection and outcome prediction.
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http://dx.doi.org/10.1016/j.ijid.2020.04.072DOI Listing
July 2020

Serum β2-Microglobulin is Associated with Mortality in Hospitalized Patients with Exacerbated Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 7;15:723-732. Epub 2020 Apr 7.

Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People's Republic of China.

Purpose: We hypothesized that increased level of serum β2-microglobulin (β2M) is an independent factor associated with higher mortality in hospitalized patients with exacerbated chronic obstructive pulmonary disease (COPD).

Patients And Methods: We retrospectively analyzed 488 hospitalized patients with exacerbated COPD as the first diagnosis at Beijing Chao-Yang hospital, P. R. China between December 31st, 2012 and December 28th, 2017. Concentrations of serum β2M and other clinical indexes were measured or collected on admission, and all patients were followed up to 90 days. The relationship between β2M and 30- and 90-day all-cause mortality was explored by Cox regression analysis adjusted for age, C-reactive protein values, N-terminal pro-brain natriuretic peptide/100, respiratory failure [RF, defined as partial arterial oxygen pressure (PaO) <60 mmHg on room air or PaO over the fraction of inspired oxygen (PaO/FiO) < 300], eosinopenia, consolidation, and acidaemia.

Results: Median concentrations of β2M were significantly higher in non-survivals compared to survivals within 30 days (4.11 mg/L (IQR 3.10-6.60) vs 2.79mg/L (IQR 2.13-3.76), < 0.001) and 90 days (3.79 mg/L (IQR 2.61-6.69) vs 2.79 mg/L (IQR 2.13-3.73), < 0.001). Serum levels of β2M were correlated with 30-day and 90-day mortality in overall exacerbated COPD patients, with hazard ratios (HRs) of 1.09 (95% CI 1.04-1.14, = 0.001) and 1.09 (95% CI 1.05-1.14, < 0.001). In exacerbated COPD patients without RF and with RF, the HRs were 1.06 (95% CI 0.995-1.137, = 0.069) and 1.14 (95% CI 1.02-1.27, = 0.021) for 30-day mortality, 1.09 (95% CI 1.02-1.15, = 0.010) and 1.14 (95% CI 1.03-1.26, = 0.014) for 90-day mortality, respectively.

Conclusion: Our data showed that concentrations of serum β2M were associated with an increased risk of mortality, suggesting that β2M might be a valuable predictor of poor prognosis for hospitalized patients with exacerbated COPD.
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http://dx.doi.org/10.2147/COPD.S243905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152914PMC
April 2020

CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway.

Biomed Pharmacother 2020 Mar 25;123:109742. Epub 2019 Dec 25.

Department of Gastric Cancer Surgery, Fudan University, Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Er Road, Shanghai 200025, China. Electronic address:

Metastasis is the main cause of gastric cancer (GC) related death and the underlying mechanisms still remain unclear. Collagen triple helix repeat containing 1 (CTHRC1) protein is known to be involved in tissue remodeling processes and closely associated with carcinogenesis and metastasis in solid tumors, but the functional role of CTHRC1 and its underlying mechanism with tumor metastasis in GC have not been fully illuminated. In the present study, CTHRC1 was highly expressed in tumor tissues and associated with poor prognosis of GC according to TCGA and GEO database. Functional studies revealed that CTHRC1 overexpression in GC significantly increased cell migration and invasion capacity. However, the promoting effects were abolished subsequent to silencing of CXCR4. In addition, CTHRC1 increased CXCR4 expression through upregulating HIF-1α expression, which eventually contributed to the promotion of cell migration and invasion. Inhibiting HIF-1α expression decreased CXCR4 expression and suppressed cell migration and invasion in GC. These results substantiated our hypothesis that HIF-1α/CXCR4 signaling pathway mediated the promoting effect of CTHRC1 on cell migration and invasion in GC.
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http://dx.doi.org/10.1016/j.biopha.2019.109742DOI Listing
March 2020

The visible nonlinear optical properties and passively Q-switched laser application of a layered PtSe material.

Nanoscale 2020 Jan;12(2):1061-1066

College of Electronic and Information Engineering, Shandong University of Science and Technology, Qingdao 266590, China.

Platinum diselenide (PtSe2), a type-II Dirac semi-metal material, is a potential saturable absorber (SA) to generate visible pulsed lasers due to its prominent optoelectronic properties. A high quality PtSe2 thin film was fabricated by combining magnetron sputtering with chemical vapor deposition methods; then, its microtopography was characterized by atomic force microscopy. The saturable absorption properties and electron relaxation time in the visible region were measured via open-aperture Z-scan and femtosecond pump probe technology, respectively. The modulation depth and saturable intensity are 39.9% and 256.6 GW cm-2, respectively. The relaxation time constants were fitted to be τ1 = (1.405 ± 0.024) ps, τ2 = (99.03 ± 0.01) ps, and τ3 = (2.032 ± 0.27) ns. The as-prepared PtSe2 thin film was experimentally applied as a novel SA to achieve a stable passively Q-switched (PQS) Pr:YLF visible laser. A shortest pulse width of 91.8 ns with a maximum repetition rate of 297.6 kHz was obtained. These results demonstrate that the PtSe2 thin film has promising applications in generating visible pulsed lasers.
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http://dx.doi.org/10.1039/c9nr08980bDOI Listing
January 2020

Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials.

Lancet Oncol 2020 02 11;21(2):261-270. Epub 2019 Dec 11.

Ignyta, San Diego, CA, USA.

Background: Recurrent gene fusions, such as ROS1 fusions, are oncogenic drivers of various cancers, including non-small-cell lung cancer (NSCLC). Up to 36% of patients with ROS1 fusion-positive NSCLC have brain metastases at the diagnosis of advanced disease. Entrectinib is a ROS1 inhibitor that has been designed to effectively penetrate and remain in the CNS. We explored the use of entrectinib in patients with locally advanced or metastatic ROS1 fusion-positive NSCLC.

Methods: We did an integrated analysis of three ongoing phase 1 or 2 trials of entrectinib (ALKA-372-001, STARTRK-1, and STARTRK-2). The efficacy-evaluable population included adult patients (aged ≥18 years) with locally advanced or metastatic ROS1 fusion-positive NSCLC who received entrectinib at a dose of at least 600 mg orally once per day, with at least 12 months' follow-up. All patients had an Eastern Cooperative Oncology Group performance status of 0-2, and previous cancer treatment (except for ROS1 inhibitors) was allowed. The primary endpoints were the proportion of patients with an objective response (complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1) and duration of response, and were evaluated by blinded independent central review. The safety-evaluable population for the safety analysis included all patients with ROS1 fusion-positive NSCLC in the three trials who received at least one dose of entrectinib (irrespective of dose or duration of follow-up). These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001).

Findings: Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018), 41 (77%; 95% CI 64-88) of 53 patients in the efficacy-evaluable population had an objective response. Median follow-up was 15·5 monhts (IQR 13·4-20·2). Median duration of response was 24·6 months (95% CI 11·4-34·8). In the safety-evaluable population, 79 (59%) of 134 patients had grade 1 or 2 treatment-related adverse events. 46 (34%) of 134 patients had grade 3 or 4 treatment-related adverse events, with the most common being weight increase (ten [8%]) and neutropenia (five [4%]). 15 (11%) patients had serious treatment-related adverse events, the most common of which were nervous system disorders (four [3%]) and cardiac disorders (three [2%]). No treatment-related deaths occurred.

Interpretation: Entrectinib is active with durable disease control in patients with ROS1 fusion-positive NSCLC, and is well tolerated with a manageable safety profile, making it amenable to long-term dosing in these patients. These data highlight the need to routinely test for ROS1 fusions to broaden therapeutic options for patients with ROS1 fusion-positive NSCLC.

Funding: Ignyta/F Hoffmann-La Roche.
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http://dx.doi.org/10.1016/S1470-2045(19)30690-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811790PMC
February 2020

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.

Lancet Oncol 2020 02 11;21(2):271-282. Epub 2019 Dec 11.

Department of Developmental Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood-brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials.

Methods: An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0-2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG (NCT02650401; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001).

Findings: Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77-18·76). 31 (57%; 95% CI 43·2-70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred.

Interpretation: Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours.

Funding: Ignyta/F Hoffmann-La Roche.
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http://dx.doi.org/10.1016/S1470-2045(19)30691-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461630PMC
February 2020

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase.

J Ovarian Res 2019 Nov 13;12(1):109. Epub 2019 Nov 13.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and regarded as the leading cause of anovulatory infertility. PCOS is characterized by reproductive dysfunction and metabolic disorders. Baicalin (BAL) is one of the most potent bioactive flavonoids isolated from the radix of Scutellaria baicalensis. In the present study, we investigated the potential effects of BAL on PCOS in dehydroepiandrosterone-treated rats. We found that BAL notably reduced the serum levels of free testosterone, total testosterone, follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol in PCOS rats. The increase of serum insulin level and HOMA-IR was markedly inhibited by BAL. Moreover, BAL decreased body weights, increased the number of rats with the regular estrous cycle, and ameliorated ovarian histological changes and follicular development in the DHEA-treated PCOS rats. The increase of pro-inflammatory cytokines (TNFα, IL-1β, and IL-18) and decrease of anti-inflammatory cytokine (IL-10) in PCOS rats were suppressed by BAL. BAL induced a significant decrease in the mRNA expression of steroidogenic enzymes, including 3β-HSD, CYP11A1, CYP19A1, StAR, in ovarian tissues in PCOS rats. Furthermore, BAL inhibited the decrease of AMPK protein level and phosphorylation, the decrease of Akt phosphorylation and the increase of 5α-reductase enzyme 1 expression in ovarian tissues in PCOS rats. The effects of BAL were inhibited by an inhibitor of AMPK, dorsomorphin. The upregulation of AMPK contributed to the beneficial effects of BAL. The results highlight the potential role of BAL for the intervention of PCOS.
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http://dx.doi.org/10.1186/s13048-019-0585-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852906PMC
November 2019

T-cell-specific mTOR deletion in mice ameliorated CD4 T-cell survival in lethal sepsis induced by severe invasive candidiasis.

Virulence 2019 12;10(1):892-901

Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.

The mammalian target of rapamycin (mTOR) pathway can mediate T-cell survival; however, the role of this pathway in T-cell survival during fungal sepsis is unclear. Here, we investigated the role of the mTOR pathway in CD4 T-cell survival in a mouse model of rapidly progressive lethal sepsis induced by severe invasive candidiasis and explored the possible mechanism. The decrease in CD4 T-cell survival following fungal sepsis was ameliorated in mice with a T-cell-specific mTOR deletion, whereas it was exacerbated in mice with a T-cell-specific tuberous sclerosis complex (TSC)1 deletion. To explore the mechanism further, we measured expression of autophagy proteins light chain 3B and p62/sequestosome 1 in CD4 T cells. Both proteins were increased in T-cell-specific mTOR knockout mice but lower in T-cell-specific TSC1 knockout mice. Transmission electron microscopy revealed that T-cell-specific mTOR knockout mice had more autophagosomes than wild-type mice following fungal sepsis. CD4 T-cell mTOR knockout decreased CD4 T-cell apoptosis in fungal sepsis. Most notably, the T-cell-specific mTOR deletion mice had an increased survival rate after fungal sepsis. These results suggest that the mTOR pathway plays a vital role in CD4 T-cell survival during fungal sepsis, partly through the autophagy-apoptosis pathway.
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http://dx.doi.org/10.1080/21505594.2019.1685151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844314PMC
December 2019

Mildew Resistance Locus O Genes and Are Negative Modulators of the Defense Response to .

Int J Mol Sci 2019 Sep 26;20(19). Epub 2019 Sep 26.

College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China.

Corynespora leaf spot caused by is one of the major diseases in cucumber ( L.). However, the resistance mechanisms and signals of cucumber to are unclear. Here, we report that the mildew resistance locus O (MLO) genes, and , are both negative modulators of the cucumber defense response to . Subcellular localization analysis showed that CsMLO1 and CsMLO2 are localized in the plasma membrane. Expression analysis indicated that the transcript levels of and are linked to the defense response to . Transient overexpression of either or in cucumber cotyledons reduced resistance to , whereas silencing of either or enhanced resistance to . The relationships of pathogenesis-related proteins, reactive oxygen species (ROS)-associated genes, and abscisic acid (ABA)-related genes to the overexpression and silencing of / in non-infested cucumber plants were investigated. The results indicated that mediated resistance against by regulating the expression of pathogenesis-related proteins and ROS-associated genes, as well as through ABA signaling pathway-associated genes. The -mediated resistance against primarily involves regulation of the expression of pathogenesis-related proteins. Our findings will guide strategies to enhance the resistance of cucumber to corynespora leaf spot.
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http://dx.doi.org/10.3390/ijms20194793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801717PMC
September 2019

Rare Primary Embryonal Carcinoma in the Brachial Plexus: A Case Report and Literature Review.

Neurosurgery 2020 08;87(2):E152-E155

Department of Orthopedic Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Background And Importance: Primary tumors of the brachial plexus are rare. Most are benign and characterized as Schwannoma and neurofibroma, whereas malignant peripheral nerve sheath tumors are less common. Here, we report a rare case of primary embryonal carcinoma in the brachial plexus.

Clinical Presentation: A 17-yr-old male presented with a 3-mo history of a mass growing in the left supraclavicular region over the middle part of the clavicle. Magnetic resonance imaging revealed a well-defined mass (diameter 2.5 cm) straddling the brachial plexus. After surgical resection, and the mass was histologically confirmed to be an embryonal carcinoma.

Conclusion: Primary embryonal carcinoma in the brachial plexus has not been reported previously. This case highlights the importance of considering the possibility that some primary brachial plexus tumors may be malignant and should be treated promptly.
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http://dx.doi.org/10.1093/neuros/nyz361DOI Listing
August 2020

A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer.

Breast Cancer Res Treat 2019 Nov 31;178(1):121-133. Epub 2019 Jul 31.

Dana-Farber Cancer Institute, Boston, MA, USA.

Purpose: This open-label, phase Ib, dose-escalation, and dose-expansion study (NCT01862081) evaluated taselisib with a taxane in locally advanced or metastatic breast cancer (BC) and/or non-small cell lung cancer (NSCLC).

Methods: Patients received taselisib (2-6 mg tablet or 3-6 mg capsule) plus docetaxel or paclitaxel. Primary endpoints were safety, dose-limiting toxicities, maximum tolerated dose, and identification of a recommended phase II dose. Secondary endpoints included pharmacokinetics and antitumor activity assessment.

Results: Eighty patients (BC: 72; NSCLC: 7; BC/NSCLC: 1) were enrolled (docetaxel-receiving arms: 21; paclitaxel-receiving arms: 59). Grade ≥ 3 adverse events (AEs), serious AEs, and AEs leading to death were reported in 90.5%, 42.9%, and 14.3% of patients, respectively (docetaxel-receiving arms), and 78.9%, 40.4%, and 3.5% of patients, respectively (paclitaxel-receiving arms). Eight patients experienced dose-limiting toxicities. The maximum tolerated dose was exceeded with 3 mg taselisib (capsule) for 21 consecutive days plus 75 mg/m docetaxel and not exceeded with 6 mg taselisib (tablet) for 5 days on/2 days off plus 80 mg/m paclitaxel. Objective response rates and clinical benefit rates were 35.0% and 45.0%, respectively (docetaxel-receiving arms), and 20.4% and 27.8%, respectively (paclitaxel-receiving arms). Exposure for paclitaxel or docetaxel plus taselisib was consistent with the single agents.

Conclusions: Taselisib in combination with a taxane has a challenging safety profile. Despite evidence of antitumor activity, the benefit-risk profile was deemed not advantageous. Further development is not planned.
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http://dx.doi.org/10.1007/s10549-019-05360-3DOI Listing
November 2019