Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Influence of Tempering Temperature on Mechanical and Rotational Bending Fatigue Properties of 40CrNi2MoE Steel.

In order to examine the mechanical properties and rotational bending fatigue performance of 40CrNi2MoE steel subsequent to tempering at varying temperatures, the steel specimen was subjected to tempering within the range of 400~460 °C. SEM, EBSD, and TEM were used to analyze the microstructure as well as precipitates. The strain hardening law was studied using the modified Crussard-Jaoult method. Investigations were undertaken to reveal the rotational bending fatigue life with respect to the tempering temperature. The findings indicate that the strength and fatigue life of the examined steels exhibit a decline as the tempering temperature increases, with the primary factor affecting this trend being the alteration in dislocation density. No notable impact on the fatigue fracture morphology exerted by tempering temperature was found within the range of the experiment. The C-J model analysis reveals that the work-hardening behavior of the trial steels is influenced by dislocations and the second phase.

First molecular detection and genetic characterization of porcine circovirus 4 in the Gansu Province of China.

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2-98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus.

Discovery of (quinazolin-6-yl)benzamide derivatives containing a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety as potent reversal agents against P-glycoprotein-mediated multidrug resistance.

P-glycoprotein (P-gp) is an important factor leading to multidrug resistance (MDR) in cancer treatment. The co-administration of anticancer drugs and P-gp inhibitors has been a treatment strategy to overcome MDR. In recent years, tyrosine kinase inhibitor Lapatinib has been reported to reverse MDR through directly interacting with ABC transporters. In this work, a series of P-gp inhibitors (1-26) was designed and synthesized by integrating the quinazoline core of Lapatinib into the molecule framework of the third-generation P-gp inhibitor Tariquidar. Among them, compound 14 exhibited better MDR reversal activity than Tariquidar. The docking results showed compound 14 displayed the L-shaped molecular conformation. Importantly, compound 14 increased the accumulation of Adriamycin (ADM) and rhodamine 123 (Rh123) in MCF7/ADM cells. Besides, compound 14 significantly increased ADM-induced apoptosis and inhibited the proliferation, migration and invasion of MCF7/ADM cells. It was also demonstrated that compound 14 significantly inhibited the growth of MCF7/ADM xenograft tumors by increasing the sensitivity of ADM. In summary, compound 14 has the potential to overcome MDR caused by P-gp.

A Study on the Fault Location of Secondary Equipment in Smart Substation Based on the Graph Attention Network.

The inability to locate device faults quickly and accurately has become prominent due to the large number of communication devices and the complex structure of secondary circuit networks in smart substations. Traditional methods are less efficient when diagnosing secondary equipment faults in smart substations, and deep learning methods have poor portability, high learning sample costs, and often require retraining a model. Therefore, a secondary equipment fault diagnosis method based on a graph attention network is proposed in this paper. All fault events are automatically represented as graph-structured data based on the K-nearest neighbors (KNNs) algorithm in terms of the feature information exhibited by the corresponding detection nodes when equipment faults occur. Then, a fault diagnosis model is established based on the graph attention network. Finally, partial intervals of a 220 kV intelligent substation are taken as an example to compare the fault localization effect of different methods. The results show that the method proposed in this paper has the advantages of higher localization accuracy, lower learning cost, and better robustness than the traditional machine learning and deep learning methods.

Ecological stoichiometry of leaf-litter-fine roots in mixed plantations in mountainous area of Southern Ningxia, China.

The southern mountainous areas in Ningxia are representative regions of the Loess Plateau, with extremely fragile ecological environment. Large area of pure plantations established during the project of Grain for Green has suffered from poor nutrient availability and biodiversity loss, while planting mixed plantations is commonly consi-dered as an effective way to improve the ecological benefits. We selected Robinia pseudoacacia + Picea asperata mixed plantation, R. pseudoacacia + Armeniaca sibirica mixed plantation, A. sibirica pure plantation and R. pseudoa-cacia pure plantation located ina Ningnan mountainous area as test objects. Based on the theory and method of ecological stoichiometry, we measured the C, N and P contents of leaves, litter and fine roots to understand nutrient cycling characteristics of different plantations. The results showed that there was significant difference in foliar stoichiometry of each tree species within the four plantations. P. asperata leaves had the highest C content in the R. pseudoacacia + P. asperata mixed plantation, and R. pseudoacacia leaves had the highest N and P contents in the R. pseudoacacia + A. sibirica mixed plantation. N content of R. pseudoacacia and A. sibirica leaves was significantly higher in mixed plantation compared with that in pure plantation. There was no significant difference in litter biomass, litter C, N, P contents and stoichiometric ratios between the pure and mixed plantations of R. pseudoacacia. Litter biomass in A. sibirica pure plantation was significantly higher than that in R. pseudoacacia + A. sibirica mixed plantation, while litter C content was significantly lower than that in the mixed plantation. Fine root biomass decreased with increasing soil depth in the four plantations, with total fine root biomass being the highest in the R. pseudoacacia + A. sibirica mixed plantation. N content and N:P of fine roots in the R. pseudoacacia + A. sibirica mixed plantation were higher than those in R. pseudoacacia and A. sibirica pure plantations. There was significant negative correlation between N content in leaves and fine roots of R. pseudoacacia + A. sibirica mixed plantation. There were significant negative correlations between the N content of leaves and litter, as well as between the P content of leaves and fine roots in the R. pseudoacacia + P. asperata mixed plantation. P content between litter and fine roots in A. sibirica pure plantation was significantly negatively correlated. Nutrient status of mixed plantations was better than pure plantations in the Ningnan mountainous area, with the mixed plantation of R. pseudoacacia and A. sibirica being the best. Mixed planting reduced nutrient limitation on plant growth to a certain extent.

Single-plane versus real-time biplane approaches for ultrasound-guided central venous catheterization in critical care patients: a randomized controlled trial.

BACKGROUND: Critical care patients often require central venous cannulation (CVC). We hypothesized that real-time biplane ultrasound-guided CVC would improve first-puncture success rate and reduce mechanical complications. The purpose of this study was to compare the success rate and safety of single-plane and real-time biplane approaches for ultrasound-guided CVC. METHODS: From October 2022 to March 2023, 256 participants with critical illness requiring CVC were randomized to either the single-plane (n = 128) or biplane (n = 128) ultrasound-guided cannulation groups. The success rate, number of punctures, procedure duration, incidence of catheterization-related complications, and confidence score of operators were documented. RESULTS: The central vein was successfully cannulated in all 256 participants (163 [64%] man and 93 [36%] women; mean age 69 ± 19 [range 13-104 years]), including 182 and 74 who underwent internal jugular vein cannulation (IJVC) and femoral vein cannulation (FVC), respectively. The incidence of successful puncture on the first attempt was higher in the biplane group than that in the single-plane group (91.6% vs. 74.7%; relative risk (RR), 1.226; 95% confidence interval (CI), 1.069-1.405; P = 0.002 for the IJVC and 90.9% vs. 68.3%; RR, 1.331; 95% CI, 1.053-1.684; P = 0.019 for the FVC). The biplane group was also associated with a higher first-puncture single-pass catheterization success rate (87.4% vs. 69.0% and 90.9% vs. 68.3%), fewer undesired punctures (1[1-1(1-2)] vs. 1[1-2(1-4)] and 1[1-1(1-3)] vs. 1[1-2(1-4)]), shorter cannulation time (205 s [162-283 (66-1,526)] vs. 311 s [243-401 (136-1,223)] and 228 s [193-306 (66-1,669)] vs. 340 s [246-499 (130-944)]), and fewer immediate complications (10.5% vs. 28.7% and 9.1% vs. 34.1%) for both IJVC and FVC (all P < 0.05). CONCLUSION: Real-time biplane imaging of ultrasound-guided CVCs offers advantages over the single-plane approach for critically ill patients. TRIAL REGISTRATION: This prospective RCT was registered at Chinese Clinical Trial Registry (ChiCTR2200064843). Registered 19 October 2022.

Hypusination-induced DHPS/eIF5A pathway as a new therapeutic strategy for human diseases: A mechanistic review and structural classification of DHPS inhibitors.

The discovery of new therapeutic strategies for diseases is essential for drug research. Deoxyhypusine synthase (DHPS) is a critical enzyme that modifies the conversion of the eukaryotic translation initiation factor 5A (eIF5A) precursor into physiologically active eIF5A (eIF5A-Hyp). Recent studies have revealed that the hypusine modifying of DHPS on eIF5A has an essential regulatory role in human diseases. The hypusination-induced DHPS/eIF5A pathway has been shown to play an essential role in various cancers, and it could regulate immune-related diseases, glucose metabolism-related diseases, neurological-related diseases, and aging. In addition, DHPS has a more defined substrate and a well-defined structure within the active pocket than eIF5A. More and more researchers are focusing on the prospect of advanced development of DHPS inhibitors. This review summarizes the regulatory mechanisms of the hypusination-induced DHPS/eIF5A pathway in a variety of diseases in addition to the inhibitors related to this pathway; it highlights and analyzes the structural features and mechanisms of action of DHPS inhibitors and expands the prospects of future drug development using DHPS as an anticancer target.

Unraveling genomic regions and candidate genes for multiple disease resistance in upland cotton using meta-QTL analysis.

Verticillium wilt (VW), Fusarium wilt (FW) and Root-knot nematode (RKN) are the main diseases affecting cotton production. However, many reported quantitative trait loci (QTLs) for cotton resistance have not been used for agricultural practices because of inconsistencies in the cotton genetic background. The integration of existing cotton genetic resources can facilitate the discovery of important genomic regions and candidate genes involved in disease resistance. Here, an improved and comprehensive meta-QTL analysis was conducted on 487 disease resistant QTLs from 31 studies in the last two decades. A consensus linkage map with genetic overall length of 3006.59 cM containing 8650 markers was constructed. A total of 28 Meta-QTLs (MQTLs) were discovered, among which nine MQTLs were identified as related to resistance to multiple diseases. Candidate genes were predicted based on public transcriptome data and enriched in pathways related to disease resistance. This study used a method based on the integration of Meta-QTL, known genes and transcriptomics to reveal major genomic regions and putative candidate genes for resistance to multiple diseases, providing a new basis for marker-assisted selection of high disease resistance in cotton breeding.

Discovery of novel thymidylate synthase (TS) inhibitors that influence cancer angiogenesis and metabolic reprogramming in NSCLC cells.

Based on previous work, further search for more effective and less damaging thymidylate synthase (TS) inhibitors was the focus of this study. After further optimization of the structure, in this study, a series of (E)-N-(2-benzyl hydrazine-1-carbonyl) phenyl-2,4-deoxy-1,2,3,4-tetrahydro pyrimidine-5-sulfonamide derivatives were synthesized and reported for the first time. All target compounds were screened by enzyme activity assay and cell viability inhibition assay. On the one hand, the hit compound DG1 could bind directly to TS proteins intracellularly and promote apoptosis in A549 and H1975 cells. Simultaneously, DG1 could inhibit cancer tissue proliferation more effectively than Pemetrexed (PTX) in the A549 xenograft mouse model. On the other hand, the inhibitory effect of DG1 on NSCLC angiogenesis was verified both in vivo and in vitro. In parallel, DG1 was further uncovered to inhibit the expression of CD26, ET-1, FGF-1, and EGF by angiogenic factor antibody microarray. Moreover, RNA-seq and PCR-array assays revealed that DG1 could inhibit NSCLC proliferation by affecting metabolic reprogramming. Collectively, these data demonstrated that DG1as a TS inhibitor could be promising in treating NSCLC angiogenesis, deserving further investigation.

GhSINA1, a SEVEN in ABSENTIA ubiquitin ligase, negatively regulates fiber development in Upland cotton.

Protein ubiquitination is essential for plant growth and responses to the environment. The SEVEN IN ABSENTIA (SINA) ubiquitin ligases have been extensively studied in plants, but information on their roles in fiber development is limited. Here, we identified GhSINA1 in Upland cotton (Gossypium hirsutum), which has a conserved RING finger domain and SINA domain. Quantitative real-time PCR (qRT-PCR) analysis showed that GhSINA1 was preferentially expressed during fiber initiation and elongation, especially during initiation in the fuzzless-lintless cotton mutant. Subcellular localization experiments indicated that GhSINA1 localized to the nucleus. In vitro ubiquitination analysis revealed that GhSINA1 has E3 ubiquitin ligase activity. Ectopic overexpression of GhSINA1 in Arabidopsis thaliana reduced the number and length of root hairs and trichomes. Yeast two-hybrid (Y2H), firefly luciferase complementation imaging (LCI), and bimolecular fluorescence complementation (BiFC) assays demonstrated that the GhSINA1 proteins could interact with each other to form homodimers and heterodimers. Overall, these results suggest that GhSINA1 may act as a negative regulator in cotton fiber development through homodimerization and heterodimerization.

[Clinical Outcome and Risk Factors of Treatment Failure of Peritoneal Dialysis Associated Peritonitis Caused by Klebsiella Pneumoniae:A Multicenter Study].

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

Characterization of Cinnamomum kanehirae Extract-Stimulated Triterpenoids Synthesis in Submerged Fermentation of Antrodia camphorata via Untargeted Metabolomics.

The underlying mechanisms of Cinnamomum kanehirae-stimulated growth and metabolism of Antrodia camphorata remain unknown. Herein, we first observed that the methanol extract of C. kanehirae trunk (MECK) (2 g/L) showed a potent stimulatory effect on A. camphorata triterpenoids production (115.6 mg/L). Second, MECK treatment considerably increased the category and abundance of many secondary metabolites in the mycelia. We identified 93 terpenoids (8 newly formed and 49 upregulated) in the MECK-treated mycelia, wherein 21 terpenoids were the same as those in the fruiting bodies. Third, 42 out of the 93 terpenoids were annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, mainly involving monoterpenoids and diterpenoids syntheses. Finally, 27 monoterpenes and 16 sesquiterpenes were detected in the MECK, and the two terpenoids with the highest abundance (linalool and α-pinene) were selected for verification and found to considerably increase the terpenoids production of A. camphorata and demonstrate the regulation of mRNA expression levels of nine key genes in the mevalonate pathway via RT-qPCR. This study is beneficial for elucidating the terpenoids synthesis mechanism in A. camphorata.

Clinical outcomes of ultrasound-guided radiofrequency ablation for solitary T1N0M0 papillary thyroid carcinoma: A retrospective study with more than 5 years of follow-up.

BACKGROUND: Ultrasound-guided radiofrequency ablation (RFA) has been used in patients with papillary thyroid carcinoma (PTC) who refuse surgery or active surveillance. However, the long-term outcomes are still limited. This study aimed to evaluate the clinical outcomes of RFA for solitary T1N0M0 PTC in a large cohort over a more than 5-year follow-up period. METHODS: This retrospective study included 358 patients with solitary T1N0M0 PTC who were treated with RFA and followed for at least 5 years. The bipolar RFA procedure was performed using hydrodissection technique, transisthmic approach, and moving-shot technique. The primary outcomes were disease progression, including lymph node metastasis (LNM), recurrent tumor, persistent tumor, and distant metastasis. The secondary outcomes were volume reduction rate, complete disappearance rate, complications, and delayed surgery. RESULTS: During a mean follow-up period of 75.5 ± 9.7 months, the overall disease progression was 5.0%. The incidence of LNM, recurrent tumor, and persistent tumor was 1.4%, 3.1%, and 0.6%, respectively. There were no significant differences in the disease progression (5.0% vs. 5.5%, p = 1.000), LNM (1.3% vs. 1.8%, p = .568), recurrent tumor (3.3% vs. 1.8%, p = .872), persistent tumors (0.3% vs. 1.8%, p = .284), and 5-year recurrence-free survival rates (95.4% vs. 96.4%, p = .785) in the T1a and T1b groups. Volume reduction rate was 100.0 ± 0.3%, with 96.9% of tumors disappearing. No complications occurred. No patients underwent delayed surgery because of anxiety. CONCLUSIONS: RFA is an effective and safe alternative for patients with T1N0M0 PTC and can offer a minimally invasive curative option for patients who refuse surgery or active surveillance. PLAIN LANGUAGE SUMMARY: During a mean follow-up period of 75.5 ± 9.7 months, the overall papillary thyroid carcinoma disease progression was 5.0%. The volume reduction rate was 100.0 ± 0.3%, with 96.9% of tumors disappearing. The T1a and T1b groups had similar incidence of disease progression and 5-year recurrence-free survival rates. No patients experienced complications or underwent delayed surgery because of anxiety.

Preoperative controlling nutritional status score (CONUT) predicts postoperative complications of patients with bronchiectasis after lung resections.

Background: The Controlled Nutritional Status (CONUT) score is a valid scoring system for assessing nutritional status and has been shown to correlate with clinical outcomes in many surgical procedures; however, no studies have reported a correlation between postoperative complications of bronchiectasis and the preoperative CONUT score. This study aimed to evaluate the value of the CONUT score in predicting postoperative complications in patients with bronchiectasis. Methods: We retrospectively analyzed patients with localized bronchiectasis who underwent lung resection at our hospital between April 2012 and November 2021. The optimal nutritional scoring system was determined by receiver operating characteristic (ROC) curves and incorporated into multivariate logistic regression. Finally, independent risk factors for postoperative complications were determined by univariate and multivariate logistic regression analyses. Results: A total of 240 patients with bronchiectasis were included, including 101 males and 139 females, with an average age of 49.83 ± 13.23 years. Postoperative complications occurred in 59 patients (24.6%). The incidence of complications, postoperative hospital stay and drainage tube indwelling time were significantly higher in the high CONUT group than in the low CONUT group. After adjusting for sex, BMI, smoking history, lung function, extent of resection, intraoperative blood loss, surgical approach and operation time, multivariate analysis showed that the CONUT score remained an independent risk factor for postoperative complications after bronchiectasis. Conclusions: The preoperative CONUT score is an independent predictor of postoperative complications in patients with localized bronchiectasis.

Impact of peritoneal dialysis modality on patient and PD survival: A systematic review.

We conducted a systematic review and meta-analysis to determine the effect of the peritoneal dialysis (PD) modality, automated peritoneal dialysis (APD) or continuous ambulatory peritoneal dialysis (CAPD), on all-cause mortality (ACM) and PD failure. Studies were identified in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure, Weipu and Wanfang databases from database inception until April 1, 2021. The inclusion and exclusion criteria were based on the Population, Intervention, Comparison, Outcome, and Study (PICOS) design. Adjusted hazard ratios (HRs) with 95% confidence intervals (CI) were used to pool outcome estimates. Seventeen studies (more than 230,000 patients) were included. Our meta-analysis showed that compared with CAPD, APD demonstrated a significantly lower ACM risk (HR 0.87 [95% CI 0.77-0.99], p = 0.04), especially in studies involving an as-treated analysis (HR 0.75 [95% CI, 0.63-0.90], p = 0.00), published in Asia (HR 0.76 [95% CI, 0.67-0.86], p < 0.001) or Europe (HR 0.81 [95% CI, 0.74-0.89], p < 0.00), or published after 2012 (HR 0.82 [95% CI, 0.68-0.99], p = 0.04). However, APD was as effective as CAPD for PD survival (HR, 0.87 [95% CI, 0.75 to 1.00], p = 0.05 or HR, 0.90 [95% CI, 0.60 to 1.35], p = 0.61). Our results demonstrate a significant survival benefit for APD and provide evidence for increasing the global use of APD, especially in developing nations, where APD use has been hampered by a lack of reimbursement for care.

Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS / 中国中药杂志

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review.

Maternal embryonic leucine zipper kinase (MELK), a member of the AMP-related serine-threonine kinase family, has been involved in regulating many cellular events, and aberrant MELK expression is associated with tumorigenesis and malignant progression in various cancers. More and more studies have found that MELK plays an essential regulatory role in tumor multidrug resistance or radio resistance. MELK inhibitors can also improve drug resistance caused by a gene mutation. These findings remind us that MELK could be a chemo- or radio-sensitizing target. However, it has also been found that most experiments on MELK rely on non-selective RNAi and small molecule reagents, which makes the results questionable, and thus the development of selective MELK inhibitors is still necessary. In this review, we summarized the identified regulatory pathways of MELK in tumor resistance and reclassified MELK inhibitors from a structural perspective. In addition, we discovered the glycosylation modification site of the MELK protein and discussed the possibility of continuing to develop small molecule inhibitors targeting the glycosylation modification site. These provide new strategies for developing selective MELK inhibitors and understanding the essential biological role of MELK in cancer.

[Immunophenotypic Features and Clinical Prognosis of Patients with Mixed Phenotype Acute Leukemia].

OBJECTIVE: To retrospectively analyze the laborotary test results and clinical data of 31 patients with mixed phenotype acute leukemia (MPAL) in order to summarize and discuss the biological characteristics, curative effect, and prognosis of each subtype of MPAL based on immunophenotype results. METHODS: MPAL patients diagnosed and treated in our hospital from July 2013 to January 2019 were selected to analyze the data of cell morphology, immunophenotyping, cytogenetics, molecular biology (MICM), and routine blood at initial diagnosis. Follow-up was carried out until the last discharge time. RESULTS: Among 31 patients, there were 19 males and 12 females, with a median age of 41(12-76) years old. According to the results of immunophenotyping and EGIL score, there were 16 cases of myeloid-T lymphoid mixed phenotype (myeloid-T group), 9 cases of myeloid-B lymphoid mixed phenotype (myeloid-B group), 5 cases of T-B lymphoid mixed phenotype (T-B group), and 1 case of myeloid-T-B lymphoid mixed phenotype. Compared between different subtypes, the antigen expression characteristics were the highest positive rate and expression rate of HLA-DR in myeloid-B group, and the positive rate of CD2 in T-B group was significantly higher than that in the myeloid-T group. Meanwhile, the expression rates of CD7 and cCD3 (cytoplasmic CD3) in T-B group were higher than those in myeloid-T group, and cCD79a was positive in all cases of myeloid-B group and T-B group. The median WBC of T-B group was 81.92×109/L, which was significantly higher than that of the other two groups (P<0.05). The quantitative results of WT1 were higher than 10-4 in 92.6% of the patients, and the WT1 expression level in myeloid-B group was significantly lower than the other two groups (P<0.01). Among the 9 patients with myeloid-B mixed phenotype, 5 cases showed BCR-ABL positive. Among 28 patients followed up, 21 cases achieved complete remission (CR), the median time to first obtain CR was 32.5(9-75) days, and the median follow-up time was 16 months (range from 21 days to 6 years). The CR rate and median overall survival (OS) time in myeloid-B group were 88.9% and 40 months, which were higher than the other two groups. The CR rate and 3-year OS rate in T-B group were relatively lower (50.0%, 0). CONCLUSION: WT1 gene is highly expressed in patients with MPAL, and each subgroup of MPAL based on immuophenotype has its unique antigen expression characteristics. Compared with myeloid-T group and T-B group, myeloid-B group can acquire higher remission rate and have better prognosis.