TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

[Alignment method for metabolite chromatographic peaks using an N-acyl glycine retention index system].

Peak alignment is a crucial data-processing step in untargeted metabolomics analysis that aims to integrate metabolite data from multiple liquid chromatography-mass spectrometry (LC-MS) batches for enhanced comparability and reliability. However, slight variations in the chromatographic separation conditions can result in retention time (RT) shifts between consecutive analyses, adversely affecting peak alignment accuracy. In this study, we present a retention index (RI)-based chromatographic peak-shift correction (CPSC) strategy to address RT shifts and align chromatographic peaks for metabolomics studies. A series of N-acyl glycine homologues (C2-C23) was synthesized as calibrants, and an LC RI system was established. This system effectively corrected RT shifts arising from variations in flow rate, gradient elution, instrument systems, and chromatographic columns. Leveraging the RI system, we successfully adjusted the RT of raw data to mitigate RT shifts and then implemented the Joint Aligner algorithm for peak alignment. We assessed the accuracy of the RI-based CPSC strategy using pooled human fecal samples as a test model. Notably, the application of the RI-based CPSC strategy to a long-term dataset spanning 157 d as an illustration revealed a significant enhancement in peak alignment accuracy from 15.5% to 80.9%, indicating its ability to substantially improve peak-alignment precision in multibatch LC-MS analyses.

Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1.

BACKGROUND: With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It's becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown. PURPOSE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI. METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF. RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-ß1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice. CONCLUSION: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.

Novel Peak Shift Correction Method Based on the Retention Index for Peak Alignment in Untargeted Metabolomics.

Peak alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based large-scale untargeted metabolomics workflows, as it enables the integration of metabolite peaks across multiple samples, which is essential for accurate data interpretation. Slight differences or fluctuations in chromatographic separation conditions, however, can cause the chromatographic retention time (RT) shift between consecutive analyses, ultimately affecting the accuracy of peak alignment between samples. Here, we introduce a novel RT shift correction method based on the retention index (RI) and apply it to peak alignment. We synthesized a series of N-acyl glycine (C2-C23) homologues via the amidation reaction between glycine with normal saturated fatty acids (C2-C23) as calibrants able to respond proficiently in both mass spectrometric positive- and negative-ion modes. Using these calibrants, we established an N-acyl glycine RI system. This RI system is capable of covering a broad chromatographic space and addressing chromatographic RT shift caused by variations in flow rate, gradient elution, instrument systems, and LC separation columns. Moreover, based on the RI system, we developed a peak shift correction model to enhance peak alignment accuracy. Applying the model resulted in a significant improvement in the accuracy of peak alignment from 15.5 to 80.9% across long-term data spanning a period of 157 days. To facilitate practical application, we developed a Python-based program, which is freely available at https://github.com/WHU-Fenglab/RI-based-CPSC.

The inflammatory cytokine profiles and ocular biometric characteristics of primary angle-closure glaucoma.

OBJECTIVE: To investigate the pathogenesis of primary angle-closure disease (PACG) by measuring the anatomical structures of the anterior and posterior segments of the eye and inflammatory markers in the peripheral blood. METHODS: This case-control study enrolled patients diagnosed with acute PACG (APACG) and chronic PACG (CPACG). It also enrolled control subjects without PACG. The anterior and posterior anatomical features were measured in all study participants. The levels of interleukin (IL)-6, tumour necrosis factor-α and the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood were measured. RESULTS: This study analysed a total of 99 eyes: 34 eyes from 34 patients with APACG, 28 eyes from 28 patients with CPACG and 37 eyes from 37 control patients with senile cataract. The axis length, corneal diameter, anterior chamber depth and anterior chamber volume were significantly smaller in the APACG and CPACG groups compared with the controls. The level of IL-6 in the peripheral blood of patients with PACG was significantly lower than that of the controls. The NLR in the peripheral blood of patients with PACG was significantly greater than that of the controls. CONCLUSIONS: Changes in the ocular anatomy and some inflammatory markers might be involved in the pathogenesis of PACG.

Research progress on chemical constituents and pharmacological effects of Ajania plants / 中国中药杂志

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

Systemic lupus erythematosus presenting with progressive massive ascites and CA-125 elevation indicating Tjalma syndrome? A case report.

BACKGROUND: Ascites, pleural effusion and raised CA-125 in the absence of malignancy in systemic lupus erythematosus is known as Tjalma syndrome. CASE SUMMARY: We report a special case of a systemic lupus erythematosus patient presenting with Tjalma syndrome. She presented with ascites and elevated CA-125 in the absence of benign or malignant ovarian tumor and no pleural effusions, which is an unusual presentation for this rare condition. CONCLUSION: Tjalma syndrome can present with massive ascites alone without pleural or pericardial effusions.

[Establishment of Drug-Resistant Cell Lines of Acute Myeloid Leukemia and Correlation of Sirt1 and PGC-1α Expression Levels with Drug Resistance].

OBJECTIVE: To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance. METHODS: Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot. RESULTS: The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001). CONCLUSION: AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.

iTRAQ based characterization of proteomic change in petroleum hydrocarbon-degrading Pseudomonas aeruginosa in different pH conditions.

In this study, a global proteomic change was characterized by iTRAQ analysis and bioinformatics analysis to study the influence by different pH conditions on proteins accumulation when Pseudomonas aeruginosa P6 degraded petroleum hydrocarbons. Compared with the condition of pH 7.2, 228 proteins in pH 5.0 and 93 proteins in pH 8.5 were identified as differentially accumulated proteins. The results further showed that in the condition of pH 5.0, fourteen chemotaxis-related proteins, two uptake-related proteins, two cytochromes, nineteen ABC transporters and five porins were downregulated, while two dioxygenases, five ß-oxidation-related proteins and one acyl-CoA metabolism-related protein were upregulated. In the condition of pH 8.5, one fimbrial protein, one aldehyde dehydrogenase, eight ABC transporters and six porins were downregulated, while five terminal oxidation-related proteins, one alcohol dehydrogenase, one ß-oxidation-related protein and one acyl-CoA metabolism-related protein were upregulated. The results indicated that in the condition of pH 5.0, chemotaxis and uptake of carbon, terminal oxidation of short-chain alkanes and transmembrane transport which are considered as key cellular processes in biodegradation of petroleum hydrocarbons in P.aeruginosa P6 may be disturbed. While in the condition of pH 8.5, the activity of transmembrane transport may decrease.

Alternating Dual-Collision Energy Scanning Mass Spectrometry Approach: Discovery of Novel Microbial Bile-Acid Conjugates.

Bile acids (BAs) are a type of gut microbiota-host cometabolites with abundant structural diversity, and they play critical roles in maintaining host-microbiota homeostasis. In this study, we developed a new N-(4-aminomethylphenyl) pyridinium (AMPP) derivatization-assisted alternating dual-collision energy scanning mass spectrometry (AMPP-dual-CE MS) method for the profiling of BAs derived from host-gut microbiota cometabolism in mice. Using the proposed method, we discovered two new types of amino acid conjugations (alanine conjugation and proline conjugation) and acetyl conjugation with host BAs, for the first time, from mouse intestine contents and feces. Additionally, we also determined and identified nine new leucine- and phenylalanine-conjugated BAs. These findings broaden our knowledge of the composition of the BA pool and provide insight into the mechanism of host-gut microbiota cometabolism of BAs.

Establishment of Drug-Resistant Cell Lines of Acute Myeloid Leukemia and Correlation of Sirt1 and PGC-1α Expression Levels with Drug Resistance / 中国实验血液学杂志

OBJECTIVE@#To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance.@*METHODS@#Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot.@*RESULTS@#The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001).@*CONCLUSION@#AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.

Multicenter real world study on the efficacy and safety of eribulin for the treatment of advanced breast cancer / 中华肿瘤杂志

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.

Aligned wave-like elastomer fibers with robust conductive layers via electroless deposition for stretchable electrode applications.

Flexible wearable electronics play an important role in the healthcare industry due to their unique skin affinity, portability and breathability. Despite great progress, it still remains a big challenge to facilely fabricate stretchable electrodes with low resistance, excellent stability and a wide tensile range. Here, we propose a handy and time-saving strategy for the fabrication of elastomeric films consisting of wave-like fibers with a robust conductive layer of silver nanoparticles (AgNPs) immobilized using polydopamine (PDA) and silicone rubber (SR). To realize better stretchability, electrospun thermoplastic polyurethane (TPU) mats with oriented nanofibers were treated via ethanol to achieve a wavy structure, which also allowed for the decoration of AgNP precursors on the TPU surface via PDA assisted electroless deposition (ELD). Therefore, the electrodes achieved a stretchability of 120% with high electrical conductivity (486 S cm-1). The films with a reduction time of 30 min showed superior electrical conductivity indicated by a resistance increase of only 100% within 50% strain. The TPU/PDA/AgNP/SR composites with a shorter reduction time of silver precursors could monitor human motions as wearable strain sensors with a wide work strain range (0-98%) and a high sensitivity (with a gauge factor (GF) of up to 81.76) for a strain of 80-98%. Therefore, they are an excellent candidate for potential application in prospective stretchable electronics.

[Systematic review and Meta-analysis of efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia].

To systematically evaluate the efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia by Meta-analysis. Randomized controlled trial(RCT) or quasi-randomized control trial(Quasi-RCT) on Ningxinbao Capsules treating arrhythmia were obtained by computer-based retrieval in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and EMbase as well as manual retrieval, with time limit from database establishment to April 7, 2020. According to the inclusion and exclusion criteria of trials, all RCTs were screened and evaluated. Then the effective data were collected and RevMan 5.3 Meta-analysis software was used for analysis. Thirteen trials were included, involving 1 379 patients in total. Ningxinbao Capsules combined with anti-arrhythmia Western medicine were adopted as the intervention, and the patients in control group were treated with the anti-arrhythmia Western medicine alone. Meta-analysis results showed that as compared to control group, Ningxinbao Capsules combined with anti-arrhythmia Western medicine group was superior in clinical efficacy, dynamic electrocardiogram and average heart rate in patients with bradycardia, with indicated statistically significant differences. Ningxinbao Capsules had fewer adverse reactions and could relieve the toxic and side effects of anti-arrhythmia medicine possibly. The study showed that Ningxinbao Capsules played a role in treatment of arrhythmia and was relatively safe. However, due to the limited quality of the included studies, high-quality clinical trials are needed to verify the conclusions.

Temperature-induced changes in the proteome of Pseudomonas aeruginosa during petroleum hydrocarbon degradation.

Petroleum hydrocarbon contaminants, which are among the most serious pollutants in the petroleum industry, can be degraded sufficiently by Pseudomonas aeruginosa. However, temperature-induced stress will severely inhibit this biodegradation. In this study, the proteome of P. aeruginosa P6 at 25 °C, 43 °C and 37 °C was used to examine the impact of temperature on the molecular mechanism of biodegradation of petroleum hydrocarbon by P. aeruginosa P6. Differentially expressed proteins were identified by iTRAQ technology, and the functions of these proteins were identified by bioinformatic analysis. The impact of 25 °C and 43 °C on cellular processes has also been discussed. The results showed that the expression of proteins in chemotaxis toward petroleum hydrocarbons, terminal oxidation of aromatic rings in petroleum hydrocarbons and trans-membrane transport of fatty acids and nutriments were clearly inhibited under 25 °C condition. The expression of proteins in chemotaxis, emulsification, adhesion and terminal oxidation of petroleum hydrocarbons; catalysis of fatty alcohols and fatty aldehydes; trans-membrane transport of nutriments and ß-oxidation were clearly inhibited under 43 °C condition.

Systematic review and Meta-analysis of efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia / 中国中药杂志

To systematically evaluate the efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia by Meta-analysis. Randomized controlled trial(RCT) or quasi-randomized control trial(Quasi-RCT) on Ningxinbao Capsules treating arrhythmia were obtained by computer-based retrieval in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and EMbase as well as manual retrieval, with time limit from database establishment to April 7, 2020. According to the inclusion and exclusion criteria of trials, all RCTs were screened and evaluated. Then the effective data were collected and RevMan 5.3 Meta-analysis software was used for analysis. Thirteen trials were included, involving 1 379 patients in total. Ningxinbao Capsules combined with anti-arrhythmia Western medicine were adopted as the intervention, and the patients in control group were treated with the anti-arrhythmia Western medicine alone. Meta-analysis results showed that as compared to control group, Ningxinbao Capsules combined with anti-arrhythmia Western medicine group was superior in clinical efficacy, dynamic electrocardiogram and average heart rate in patients with bradycardia, with indicated statistically significant differences. Ningxinbao Capsules had fewer adverse reactions and could relieve the toxic and side effects of anti-arrhythmia medicine possibly. The study showed that Ningxinbao Capsules played a role in treatment of arrhythmia and was relatively safe. However, due to the limited quality of the included studies, high-quality clinical trials are needed to verify the conclusions.

Chloroplast Genome Sequences and Comparative Analyses of Combretaceae Mangroves with Related Species.

In the Combretaceae family, only two species of Lumnitzera and one species of Laguncularia belong to mangroves. Among them, Lumnitzera littorea (Jack) Voigt. is an endangered mangrove plant in China for the limited occurrence and seed abortion. In contrast, Lumnitzera racemosa Willd. is known as the most widespread mangrove plant in China. Laguncularia racemosa C. F. Gaertn., an exotic mangrove in China, has the fast growth and high adaptation ability. To better understand the phylogenetic positions of these mangroves in Combretaceae and in Myrtales and to provide information for studies on evolutionary adaptation for intertidal habitat, the complete chloroplast (cp) genomes of Lu. racemosa and La. racemosa were sequenced. Furthermore, we present here the results from the assembly and annotation of the two cp genomes, which were further subjected to the comparative analysis with Lu. littorea cp genomes we published before and other eleven closely related species within Myrtales. The chloroplast genomes of the three Combretaceae mangrove species: Lu. littorea, Lu. racemosa, and La. racemosa are 159,687 bp, 159,473 bp, and 158,311 bp in size. All three cp genomes host 130 genes including 85 protein-coding genes, 37 tRNAs, and 4 rRNAs. A comparative analysis of those three genomes revealed the high similarity of genes in coding-regions and conserved gene order in the IR and LSC/SSC regions. The differences between Lumnitzera and Laguncularia cp genomes are the locations of rps19 and rpl2 genes in the IR/SC boundary regions. Investigating the effects of selection events on shared protein-coding genes showed a relaxed selection had acted on the ycf2, ycf1, and matK genes of Combretaceae mangroves compared to the nonmangrove species Eucalyptus aromaphloia. The phylogenetic analysis based on the whole chloroplast genome sequence with one outgroup species strongly supported three Combretaceae mangroves together with other two Combretaceae species formed a cluster in Combretaceae. This study is the first report on the comparative analysis of three Combretaceae mangrove chloroplast genomes, which will provide the significant information for understanding photosynthesis and evolution in Combretaceae mangrove plants.

Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice / 北京大学学报(医学版)

OBJECTIVE@#Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world.@*METHODS@#We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated.@*RESULTS@#Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3.@*CONCLUSION@#Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

A Global Proteomic Change in Petroleum Hydrocarbon-Degrading Pseudomonas aeruginosa in Response to High and Low Concentrations of Petroleum Hydrocarbons.

In this study, iTRAQ analysis and bioinformatics analysis were used to reveal the changes in key proteins induced by different concentrations of petroleum hydrocarbons during the biodegradation of petroleum hydrocarbons in Pseudomonas aeruginosa P6. Sixty-three proteins were identified as differentially expressed proteins, and all of them were strongly associated with the cellular processes related to the biodegradation of petroleum hydrocarbons. The results further showed that among the differentially expressed proteins, 3 chemotaxis-related proteins, 10 terminal oxidation of short-chain alkane-related proteins, and 13 transmembrane transport-related proteins were down regulated, while 1 uptake of petroleum hydrocarbon-related protein, 3 terminal oxidation of long-chain alkane-related proteins, 4 dehydrogenation-related proteins, 12 ß-oxidation-related proteins, and 2 metabolisms of acyl-CoA-related proteins were up regulated. These results indicated that during the biodegradation of petroleum hydrocarbons in P. aeruginosa P6, the activity of chemotaxis, the terminal oxidation of short-chain alkanes, and transmembrane transport decreased, while the activity of the uptake of petroleum hydrocarbons, the terminal oxidation of long-chain alkanes, dehydrogenation, ß-oxidation, and the metabolism of acyl-CoA increased under the 20,000 mg/L petroleum hydrocarbon condition compared with the 500 mg/L petroleum hydrocarbon condition. The findings revealed changes in the key proteins and the corresponding cellular process of the biodegradation of petroleum hydrocarbons in P. aeruginosa P6 under high and low concentrations of petroleum hydrocarbons and provided references for future studies.

[Stress and coping style in children and adolescents with type 1 diabetes and their influence on disease self-management].

OBJECTIVE: To investigate the influence of demographic and clinical characteristics, stress, and coping style on disease self-management in children and adolescents with type 1 diabetes. METHODS: A cross-sectional survey was performed to select 149 children and adolescents with type 1 diabetes (aged 8-20 years). Related data were collected using the questionnaires and scales on general information, diabetes self-management, perceived stress, and coping style. RESULTS: Of the 149 children and adolescents, 37(24.8%) had high stress. Compared with the school-aged children, the adolescents had higher stress level and were more likely to present with negative coping style (P<0.05). The multiple linear regression analysis showed that the children whose mothers had an educational level at or above senior high school, who had a low stress level, and who adopted positive coping measures had a higher level of diabetes self-management (P<0.05). CONCLUSIONS: Nearly a quarter of the children and adolescents with type 1 diabetes have a high stress level. When delivering the education on diabetes self-management to children and adolescents, healthcare workers should focus on the families whose mothers have an educational level at or below junior high school. Strategies should aim at reducing stress by encouraging positive coping styles.