The anticancer therapeutic potential of pyrimidine-sulfonamide hybrids.

Cancer as a devastating malignancy, seriously threatens human life and health, but most chemotherapeutics have long been criticized for unsatisfactory therapeutic efficacy due to drug resistance and severe off-target toxicity. Pyrimidines, including fused pyrimidines, are privileged scaffolds for various biological cancer targets and are the most important class of metalloenzyme carbonic anhydrase inhibitors. Pyrimidine-sulfonamide hybrids can act on different targets in cancer cells simultaneously and possess potent activity against various cancers, revealing that hybridization of pyrimidine with sulfonamide is a promising approach to generate novel effective anticancer candidates. This review aims to summarize the recent progress of pyrimidine-sulfonamide hybrids with anticancer potential, covering papers published from 2020 to present, to facilitate further rational design of more effective candidates.

[Box: see text].

Bioinformatics analysis and clinical significance of NRP-1 in triple-negative breast cancer.

Purpose: This study aimed to investigate the diagnostic and prognostic values of neuropilin-1 (NRP-1) in triple-negative breast cancer (TNBC) and analyze its immune function in the tumor microenvironment. Methods: Based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, Genotype Tissue Expression, Immune Cell Abundance Identifier (ImmuCellAI), Reactome, and Genomics of Drug Sensitivity in Cancer databases, the cancer tissues from 50 patients with TNBC and corresponding adjacent noncancerous tissues from 10 patients (tissue microarrays were purchased from Shanghai Xinchao Biotechnology Co., Ltd.) were collected for validation. Bioinformatics combined with immunohistochemistry was used to analyze the relationship among NRP-1 expression, prognosis, tumor immune cell infiltration, immune genes, and drug resistance so as to investigate the role of NRP-1 in the development of TNBC. Results: A significant difference in NRP-1 gene expression was found between the cancerous and noncancerous tissues (p-value < 0.05); NRP-1 expression was high in carcinoma. No significant correlation was found between NRP-1 protein expression levels and each stage in the TCGA database. Prognostic expression survival analysis showed that the survival probability of patients with high NRP-1 expression was significantly lower than that of patients with low NRP-1 expression (p-value < 0.05), suggesting that the gene might be a pro-oncogene. The data from 50 clinical samples also confirmed that the NRP-1 expression was significantly higher in triple-negative breast cancer (TNBC) tissues than in adjacent noncancerous tissues. The NRP-1 expression significantly correlated with the tumor diameter and pathological grade (p-value < 0.05), but not with age, stage, and ki67 (p-value > 0.05). The Kaplan-Meier survival curves suggested that the median overall survival was significantly shorter in patients with high NRP-1 expression than in those with low NRP-1 expression (13.6 months vs 15.2 months, p-value < 0.05). The 300 genes most significantly positively associated with this gene were selected for Gene Ontology (including Biological Process, Molecular Function, and Cellular Component groups) and Kyoto Encyclopedia of Genes and Genomics enrichment analysis. The findings showed that NRP-1 was involved in immune regulation in TNBC. In addition, the NRP-1 expression in TNBC positively correlated with a variety of immune cells and checkpoints. Conclusion: NRP-1 can be used as a potential biomarker and therapeutic target in TNBC.

Discovery of the tigecycline resistance gene cluster tmexCD3-toprJ1 in Pasteurella multocida strains isolated from pigs in China.

Pasteurella multocida is a leading cause of respiratory disorders in pigs. However, the genotypes and antimicrobial resistance characteristics of P. multocida from pigs in China have not been reported frequently. In this study, we investigated 381 porcine strains of P. multocida collected in China between 2013 and 2022. These strains were assigned to capsular genotypes A (69.55%, n = 265), D (27.82%, n =106), and F (2.62%, n = 10); or lipopolysaccharide genotypes L1 (1.31%, n = 5), L3 (24.41%, n = 93), and L6 (74.28%, n = 283). Overall, P. multocida genotype A:L6 (46.46%) was the most-commonly identified type, followed by D:L6 (27.82%), A:L3 (21.78%), F:L3 (2.62%), and A:L1 (1.31%). Antimicrobial susceptibility testing showed that a relatively high proportion of strains were resistant to tetracycline (66.67%, n = 254), and florfenicol (35.17%, n = 134), while a small proportion of strains showed resistance phenotypes to enrofloxacin (10.76%, n = 41), ampicillin (8.40%, n = 32), tilmicosin (7.09%, n = 27), and ceftiofur (2.89%, n = 11). Notably, Illumina short-read and Nanopore long-read sequencing identified a chromosome-borne tigecycline-resistance gene cluster tmexCD3-toprJ1 in P. multocida. The structure of this cluster was highly similar to the respective structures found in several members of Proteus or Pseudomonas. It is assumed that the current study identified the tmexCD3-toprJ1 cluster for the first time in P. multocida.

The causal relationship between ankylosing spondylitis and the risk of ovarian cancer.

OBJECTIVE: The aim of this study was to investigate the potential causal relationship between ankylosing spondylitis (AS) and ovarian cancer. METHODS: We conducted analyses utilizing publicly available pooled statistical data sets from genomewide association studies (GWAS) involving individuals of European ancestry. Our objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with AS and use them as instrumental variables to assess the causal relationship between AS and ovarian cancer. We employed three statistical methods for two-sample Mendelian randomization: inverse variance weighting (IVW), weighted median, and MR-Egger regression. Network MR Analysis revealed the mediating role of tumor necrosis factor receptor superfamily member 21 between ankylosing spondylitis and ovarian cancer. RESULTS: From the GWAS on AS, we selected 23 instrumental SNPs that exhibited genome-wide significance. Our findings consistently demonstrated an association between AS and ovarian cancer using multiple statistical methods (IVW: odds ratio (OR) 1.147, 95% confidence interval (CI) 1.022-1.287; weighted median estimator: OR 1.177, 95% CI 1.009-1.373; MR-Egger regression: OR 1.166, 95% CI 0.958-1.418). These results indicate a positive correlation, suggesting that AS is associated with an increased risk of ovarian cancer. Furthermore, there was no evidence to suggest that the observed causal effect between AS and the risk of osteoarthritis was influenced by genetic pleiotropy (MR-Egger intercept = -0.0010644, P = 0.8433359). In addition, tumor necrosis factor receptor superfamily member 21 mediated 10.2% of the total effect size in the development of ankylosing spondylitis on ovarian cancer risk. CONCLUSION: Our Mendelian randomization analysis provides strong evidence supporting a potential causal relationship between AS and ovarian cancer risk, with ankylosing spondylitis clearly associated with an increased risk of ovarian cancer. Tumor necrosis factor receptor superfamily member 21 as a mediator involved in the occurrence and development of these two diseases.

Identification of two-component system ArcAB and the universal stress protein E in Pasteurella multocida and their effects on bacterial fitness and pathogenesis.

Two-component regulatory system (TCS) is a widespread bacterial signal transduction mechanism and plays a critical role in bacterial adaptation to environments as well as regulating bacterial virulence. However, few studies have reported the actions of TCS in Pasteurella multocida, a zoonotic bacterial pathogen. In this study, genes encoding proteins homologous to the ArcAB TCS were identified in genome sequences of P. multocida belonging to different serogroups, and the transcription of both arcA and arcB was up-regulated in anaerobic and superoxygen environment. Compared to wild type strains, P. multocida arcA-deletion mutants (ΔarcA) displayed a decrease in growing under anaerobic conditions, biofilm formation, as well as the capacities of anti-serum bactericidal effect, cell adherence and invasion, anti-phagocytosis, and virulence in different in vivo models (Galleria mellonella and mice). RNA-Seq identified 70 significantly downregulated genes in ΔarcA compared to the wild type strain, and several of them are associated with P. multocida virulence. Among them, a universal stress protein E encoding gene uspE was characterized in P. multocida for the first time. Electrophoretic mobility shift assay (EMSA) demonstrated that the ArcAB TCS could regulate uspE directly. Deletion of uspE also led to a decrease of P. multocida in growing under anaerobic conditions, biofilm formation, anti-serum bactericidal effect, cell adherence and invasion, anti-phagocytosis, and virulence in mice. The data provided from this study will help further understanding the fitness and pathogenesis of P. multocida.

Discrimination of blood metabolomics profiles in neonates with idiopathic polyhydramnios.

This study aimed to compare the blood metabolic status of neonates with idiopathic polyhydramnios (IPH) and those with normal amniotic fluid, and to explore the relationship between IPH and fetal health. Blood metabolites of 32 patients with IPH and 32 normal controls admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between January 2017 and December 2022 were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) and metabolite enrichment analyses were performed to identify the differential metabolites and metabolic pathways. There was a significant difference in the blood metabolism between newborns with IPH and those with normal amniotic fluid. Six discriminant metabolites were identified: glutamate, serine, asparagine, aspartic acid, homocysteine, and phenylalanine. Differential metabolites were mainly enriched in two pathways: aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism. CONCLUSIONS: This study is the first to investigate metabolomic profiles in newborns with IPH and examine the correlation between IPH and fetal health. Differential metabolites and pathways may affect amino acid synthesis and the nervous system. Continuous attention to the development of the nervous system in children with IPH is necessary. WHAT IS KNOWN: • There is an increased risk of adverse pregnancy outcomes with IPH, such as perinatal death, neonatal asphyxia, neonatal intensive care admission, cesarean section rates, and postpartum hemorrhage. • Children with a history of IPH have a higher proportion of defects than the general population, particularly central nervous system problems, neuromuscular disorders, and other malformations. WHAT IS NEW: • In neonates with IPH, six differential metabolites were identified with significant differences and good AUC values using LC-MS/MS analysis: glutamic acid, serine, asparagine, aspartic acid, homocysteine, and phenylalanine, which were mainly enriched in two metabolic pathways: aminoacyl-tRNA biosynthesis and alanine, aspartate, and glutamate metabolism. • These differential metabolites and pathways may affect amino acid synthesis and development of the nervous system in neonates with IPH.

Increased acylcarnitine ratio indices in newborn screening for carnitine-acylcarnitine translocase deficiency shows increased sensitivity and reduced false-positivity.

Background: Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive metabolic disorder of mitochondrial long-chain fatty acid oxidation. Newborn screening via tandem mass spectrometry (MS/MS) technology enables early diagnosis. However, previous analyses of MS/MS data of patients showed that some results were misdiagnosed because they did not show typical acylcarnitine profiles of CACT deficiency. This study aimed to identify additional indices to assist the diagnosis of CACT deficiency. Methods: To evaluate the acylcarnitine profile and the acylcarnitine ratios of individuals with CACT deficiency, the MS/MS data of 15 patients diagnosed via genetic testing were retrospectively analysed. The sensitivity and false-positive rates of primary acylcarnitine markers and ratio indices were validated using the data from 28,261 newborns and 53 false-positive cases. Additionally, the MS/MS data of 20 newborns carrying the c.199-10T>G mutation in SLC25A20 and 40 normal controls were compared to verify whether the carriers had abnormal acylcarnitine concentrations. Results: The acylcarnitine profiles from 15 patients were classified into three categories using C12, C14, C16, C18, C16:1, C18:1, and C18:2 as the primary diagnostic markers. The first category represented a typical profile (P1-P6). The second category for patients P7 and P8 showed a significant decrease in the C0 level and a normal concentration of long-chain acylcarnitines. The third category for patients P9-P15 showed the presence of interfering acylcarnitines. The second and third categories may have been misdiagnosed. An acylcarnitine ratio analysis showed that C14/C3, C16/C2, C16/C3, C18/C3, C16:1/C3, and C16:1-OH/C3 were significantly increased in all 15 patients. The verification of 28,261 newborn screening results showed that the false-positive rate of ratios, except for (C16 + C18)/C0, was lower than that of acylcarnitine indices (0.02-0.08% vs. 0.16-0.88%). None of the single long-chain acylcarnitines could separate patients from the false-positive cases; however, all ratios produced good discrimination between the two groups. Conclusions: Based on the primary acylcarnitine markers alone, CACT deficiency can be misdiagnosed in newborn screening. The ratios of the primary markers (C16 + C18:1)/C2, C16/C2, C16:1/C3, and C16:1-OH/C3 can facilitate the diagnosis of CACT deficiency, thereby increasing sensitivity and reducing false-positivity.

Systematic pan-cancer analysis identified neuropilin 1 as an immunological and prognostic biomarker.

Neuropilin 1 (NRP1) is a transmembrane glycoprotein, nontyrosine kinase receptor that plays an important role in axonal growth and angiogenesis in the nervous system. Although currently more and more studies have shown that NRP1 plays an important role in some cancers, no systematic pan-cancer analysis of NRP-1 has been performed to date. Therefore, we aimed to investigate the associated immune function and prognostic value of NRP1 in 33 tumors of various cancer types. In this study, based on The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue Expression, cBioportal for cancer genomics, and Human Protein Atlas (HPA databases), various bioinformatics analysis methods were used to investigate the potential carcinogenic effects of NRP1 activation, pan-cancer analysis of NRP1 expression, and the relationship between NRP1 expression and prognosis indicators including overall survival, disease-specific survival, disease-free interval, and progression-free interval, tumor mutational burden (TMB), and microsatellite instability (MSI). The results showed that NRP1 was highly expressed in most tumors. In addition, NRP1 was found to be positively or negatively correlated with the prognosis of different tumors. Also, the expression of NRP1 was associated with TMB and MSI in in 27 and 21 different types of tumors, respectively, and with DNA methylation in almost all the various types of tumors. The expression of the NRP1 gene was negatively correlated with the infiltration levels of most immune cells. In addition, the correlation between the level of immune cell infiltration and NRP1 expression varied according to immune cell subtype. Our study suggests that NRP1 plays an important role in tumor development and tumor immunity and could potentially be used as a prognostic indicator in a variety of malignancies.

Vascular Endothelial Growth Factor A Contributes to Increased Mammalian Respiratory Epithelial Permeability Induced by Pasteurella multocida Infection.

Pasteurella multocida infection can cause significant zoonotic respiratory problems in both humans and animals, but little is known about the mechanisms used by P. multocida to invade and cross the mammalian respiratory barrier. In this study, we investigated the influence of P. multocida infection on the dysfunction of the respiratory epithelial barrier. In vivo tests in mouse infection models demonstrated that P. multocida infection significantly increased epithelial permeability and increased the expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) in murine tracheae and lungs. In murine lung epithelial cell (MLE-12) models, P. multocida infection decreased the expression of tight junctions (ZO-1) and adherens junctions (ß-catenin and E-cadherin) proteins but induced the activation of hypoxia-inducible factor 1α (HIF-1α) and VEGFA signaling. When the expression of HIF-1α is suppressed, the induction of VEGFA and ZO-1 expression by P. multocida infection is decreased. We also found that intervention of HIF-1α and VEGFA signaling affected infection outcomes caused by respiratory bacteria in mouse models. Most importantly, we demonstrate that P. multocida infection increases the permeability of human respiratory epithelial cells and that this process is associated with the activation of HIF-1α and VEGFA signaling and likely contributes to the pathogenesis of P. multocida infection in humans. IMPORTANCE The mammalian respiratory epithelium forms the first line of defense against infections with P. multocida, an important zoonotic respiratory pathogen. In this study, we found that P. multocida infection increased respiratory epithelial permeability and promoted the induction of the HIF-1α-VEGFA axis in both mouse and murine cell models. Similar findings were also demonstrated in human respiratory epithelial cells. The results from this study provide important knowledge about the pathogenesis of P. multocida causing infections in both animals and humans.

[Blood metabolites in preterm infants with retinopathy of prematurity based on tandem mass spectrometry: a preliminary study]. / åŸºäºŽè´¨è°±æŠ€æœ¯çš„æ—©äº§å„¿è§†ç½‘è†œç— è¡€ä»£è°¢äº§ç‰©çš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics. METHODS: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers. RESULTS: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP. CONCLUSIONS: Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

[Analysis of clinical characteristics and genetic variant in a child with Nicolaides-Baraitser syndrome due to maternal mosaicism].

OBJECTIVE: To carry out genetic testing for a child featuring global developmental delay, abnormal liver function, congenital heart disease, and brain malformation. METHODS: Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored a heterozygous c.2002G>T (p.Glu668Ter) variant of the SMARCA2 gene, which was predicted to be likely pathogenic by bioinformatic analysis. His mother was found to be a low-percentage mosaic for the same variant, with a ratio of 0.054 (246/4549). CONCLUSION: The child was diagnosed with Nicolaides-Baraitser syndrome resulting from maternal mosaicism for the SMARCA2 gene variant.

Carbon Black/Multi-Walled Carbon Nanotube-Based, Highly Sensitive, Flexible Pressure Sensor.

Flexible piezoresistive pressure sensors have promising applications in wearable devices, artificial intelligence, and other fields. However, developing low-cost and high-performance pressure sensors still poses a great challenge. Herein, we utilize low-cost carbon black (CB) and multi-walled carbon nanotubes (MWCNTs) mixed in porous polydimethylsiloxane to assemble a flexible piezoresistive pressure sensor combined with interdigitated electrodes. Simultaneously, the COMSOL Multiphysics simulation analysis was performed to predict the sensing behavior of the pressure sensor, which was verified by experiments; the preparation of the pressure sensor was guided according to the prediction. Additionally, we studied the effects of the mixed conductive filler's weight ratio, the shape of the interdigital electrode, and the line width and spacing of the interdigital electrode on the performance of the sensor. Based on the interaction of the 3D porous structure and the synergistic conductive network of CB/MWCNTs, the prepared pressure sensor exhibits a high sensitivity of 3.57 kPa-1 (∼21 kPa), a wide detection range of 0-275 kPa, fast response time (96 ms), fast recovery time (198 ms), good durability (about 3000 cycles), and good flexibility. Moreover, the fabricated sensor can monitor and recognize human activities (such as finger bending and mouse clicking), indicating that it has great potential in flexible wearable devices and other fields. It is worth noting that the preparation process of the entire pressure sensor was simple, low cost, and environmentally friendly, which provides a certain basis for industrial and commercial applications.

Serum differential proteomic profiling of patients with isolated methylmalonic acidemia by iTRAQ.

Isolated methylmalonic acidemia (MMA) is an inherited organic acid metabolic disorder in an autosomal recessive manner, caused by mutations in the methylmalonyl coenzyme A mutase gene, and the isolated MMA patients often suffer from multi-organ damage. The present study aimed to profile the differential proteome of serum between isolated MAA patients and healthy control. The in vivo proteome of isolated MAA patients and healthy subjects was detected by an isobaric tag for relative and absolute quantitation (iTRAQ). A total of 94 differentially expressed proteins (DEPs) were identified between MMA patients and healthy control, including 58 upregulated and 36 downregulated DEPs in MMA patients. Among them, the most significantly upregulated proteins were CRP and immunoglobulins, and the top five most significantly downregulated proteins were all different types of immunoglobulins in MMA patients. GO analysis showed that these DEPs were mainly enriched in immune-related function and membrane protein-related function. KEGG revealed that these DEPs were mainly enriched in lysosome and cholesterol metabolism pathways. Also, these DEPs were predicted to contribute to lipid metabolic diseases. We addressed the proteomes of isolated MMA patients and identified DEPs. Our study expands our current understanding of MMA, and the DEPs could be valuable for designing alternative therapies to alleviate MMA symptoms.

Prenatal Diagnosis of Two Common Inborn Errors of Metabolism by Genetic and Mass Spectrometric Analysis of Amniotic Fluid.

Methylmalonic acidaemia (MMA) and ornithine transcarbamylase deficiency (OTCD) are both intoxication-type inborn errors of metabolism (IEM). Presently, genetic testing is the primary method for prenatally diagnosing these diseases. However, some reports have demonstrated that mass spectrometry approaches can prenatally diagnose some forms of inborn errors of metabolism using amniotic fluid. Therefore, in this study, genetic and mass spectrometry approaches were used for prenatally diagnosing MMA and OTCD. We collected amniotic fluid samples from 19 foetuses referred, 15 cases were referred for MMA and 4 for OTCD. Of the 15 MMA cases, seven were affected, as determined by genetic testing and the metabolite levels; the characteristic metabolites propionylcarnitine (C3), C3/acetylcarnitine (C2) ratio, methylmalonic acid and methylcitrate levels were significantly higher than the reference range. Eight foetuses were unaffected, and the C3, C3/C2 ratio, methylmalonic acid and methylcitrate levels were within the reference range. The C3, C3/C2, methylmalonic acid, and methylcitrate levels in the amniotic fluid significantly differed between the affected and unaffected foetuses (P = 0.0014, P = 0.0014, P = 0.0003, P = 0.0014, respectively). Moreover, the homocysteine level increased in the amniotic fluid of affected foetuses with MMACHC gene mutations. Of the four OTCD cases, genetic testing confirmed that two foetuses were affected and two were unaffected. However, the characteristic metabolite levels were within the reference range for all foetuses, including citrulline, orotic acid, and uracil. The genetic testing results were confirmed to be correct through the abortion tissue of the foetus and the postnatal follow-up. Our results suggest that mass spectrometry approaches are convenient method for improving the prenatal diagnosis of MMA. The characteristic metabolites C3, C3/C2, methylmalonic acid, and methylcitrate levels in amniotic fluid were reliable biochemical markers for the prenatal diagnosis of MMA.

Identification of triple gene fusion ALK-LRRN2, LTBP1-ALK, and HIP1-ALK in advanced lung adenocarcinoma and response to alectinib: A case report.

RATIONALE: Anaplastic lymphoma kinase (ALK) rearrangement is the second most common targetable oncogene-dirven gene in nonsmall cell lung cancer. Owing to the advanced sequencing technologies, new partner genes of ALK have been constantly detected. PATIENT CONCERNS: A 42-year-old Chinese woman went to our hospital with the chief complaint of cough and expectoration for 1 month. The patient had no fever, chest pain, and hemoptysis. DIAGNOSES: She was diagnosed with advanced lung adenocarcinoma. The patient underwent lung biopsy guided by computed tomography and pathology showed poorly differentiated adenocarcinoma. To explore possibility of targeted therapy, the tumor samples were subjected to next-generation sequencing, and a rare 3 ALK fusion variant ALK-LRRN2, LTBP1-ALK, and HIP1-ALK was identified. INTERVENTIONS AND OUTCOMES: The patient subsequently received alectinib treatment, and achieved partial response. No significant drug related adverse reactions were found during alectinib treatment. The progression-free survival achieved 25 months. LESSONS: Together, we identified a rare triple ALK fusion variant, ALK-LRRN2, LTBP1-ALK and HIP1-ALK, in a patient with lung adenocarcinoma. The patient benefited from alectinib treatment, which could provide a certain reference for the patients with such gene alteration.

Impact of humanized nursing care on negative emotions and quality of life of patients with mental disorders.

OBJECTIVE: To explore the impact of humanized nursing care on negative emotions and quality of life (QOL) of patients with mental disorders. METHODS: Among the 112 patients with mental disorders treated in our hospital from July, 2017 to November, 2019, 53 who received routine care served as the control group and 59 who received humanized nursing care were in the observation group. Changes in self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were compared for mental status assessment, and the generic quality of life inventory-74 (GQOL-74) was used to evaluate their QOL. Besides, patient satisfaction, scores of activity of daily living (ADL) scale and mini-mental state examination (MMSE) were compared after intervention. RESULTS: After intervention, patients in the observation group had higher scores in the self-rating anxiety scale, self-rating depression scale, the generic quality of life inventory-74, and mini-mental state examination, and lower scores in the activities of daily living scale; they also presented a higher overall satisfaction than those in control group. CONCLUSION: Humanized nursing care contributes to the relief of negative emotions and the enhancement of quality of life of patients with mental disorders, which is worth popularizing in clinical nursing services.

Determination of risk factors for fever after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

ABSTRACT: This study was to identify risk factors affecting postembolization fever (PEF) of CalliSpheres drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of primary hepatocellular carcinoma (HCC).One hundred eighty-eight consecutive patients with HCC who underwent DEB-TACE with fever between June 2017 and May 2019 were included in this retrospective study. The patients were divided into 4 groups based on the severity of posttransarterial chemoembolization (TACE) fever according to the degrees of body temperature. Univariate analysis and multivariate logistics regression were performed to identify potential risk factors for post-TACE fever.In the stepwise multiple regression analysis, pre-TACE blood urea, small particle size and Cental liqefction (P < .05) were independent risk factors of severe post-TACE fever (P < .05, respectively). Portal vein thrombosis (P < .01), Child-Pugh stage (P < .01), and cycles of DEB-TACE (P < .05) were independent risk factors for clinical death, PEF was not associated with clinical death (P = .754) and 6-month survival (P = .524) in the univariate analysis. Moreover, multivariate Cox regression was performed, and Child-Pugh stage (B vs A) (P = .040) and portal vein thrombosis (yes vs no) (P = .033) were independent factors predicting unfavorable overall survival in HCC patients.Pre-TACE blood urea, small particle size, and Cental liqefction were significantly correlated with the occurrence fever after DEB-TACE. Therefore, these factors should be taken into full consideration for the relief of fever. However, PEF after D-TACE was not associated with clinical death and 6-month survival rate.

Uniform Water Potential Induced by Salt, Alkali, and Drought Stresses Has Different Impacts on the Seedling of Hordeum jubatum: From Growth, Photosynthesis, and Chlorophyll Fluorescence.

Hordeum jubatum is a halophyte ornamental plant wildly distributed in the Northeast of China, where the low water potential induced by various abiotic stresses is a major factor limiting plant growth and development. However, little is known about the comparative effects of salt, alkali, and drought stresses at uniform water potential on the plants. In the present study, the growth, gas exchange parameters, photosynthetic pigments, and chlorophyll fluorescence in the seedlings of H. jubatum under three low water potentials were measured. The results showed that the growth and photosynthetic parameters under these stresses were all decreased except for carotenoid (Car) with the increasing of stress concentration, and alkali stress caused the most damaging effects on the seedlings. The decreased net photosynthetic rate (Pn), stomatal conductance (Gs), and intercellular CO2 concentrations (Ci) values under salt stress were mainly attributed to stomatal factors, while non-stomatal factors were dominate under drought and alkali stresses. The reduced chlorophyll and slightly increased Car contents occurred under these stresses, and most significant changed under alkali stress. In addition, the maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency (ΦPSII), and photochemical quenching coefficient (qP) under the stresses were all decreased, indicating that salt, alkali, and drought stresses all increased susceptibility of PSII to photoinhibition, reduced the photosynthetic activity by the declined absorption of light for photochemistry, and increased PSII active reaction centers. Moreover, the non-photochemical quenching coefficient (NPQ) of alkali stress was different from salt and drought stresses, showing that the high pH of alkali stress caused more damaging effects on the photoprotection mechanism depending on the xanthophyll cycle. The above results suggest that the H. jubatum has stronger tolerance of salt than drought and alkali stresses, and the negative effects of alkali stress on the growth and photosynthetic performance of this species was most serious.

Short-term efficacy and safety of callispheres drug-loaded microsphere embolization in primary hepatocellular carcinoma.

BACKGROUND: Drug-eluting beads transarterial chemoembolization (DEB-TACE) is a newly developed local regional therapy for improving the efficacy and safety of conventional transarterial chemoembolization (cTACE), which is now universally used to treat patients with unresectable liver cancer.Cohort studies, clinical trials, and meta-analysis have shown DEB-TACE to be associated with favorable treatment responses, prolonged survival, and at least similar safety profile when compared with cTACE. AIMS AND OBJECTIVES: This study was to evaluate the short term clinical efficacy, side effects, and risk factors affecting the clinical effectiveness of CalliSpheres drug loaded bead transcatheter arterial chemoembolization (DEB TACE) in the treatment of primary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 172 consecutive patients with HCC undergoing DEB TACE (loaded with doxorubicin) from January 2017 to December 2018 were prospectively enrolled. Short term local tumor response was evaluated by the modified RECIST criteria. Postoperative complications and liver function disorders were analyzed based on examinations and clinical symptoms. RESULTS: The median follow up period was 310 days. Based on the modified response evaluation criteria in solid tumors criteria, objective response rates(complete response [CR] + partial response [PR]) were 78.7%, 71.6%, and 63.2%, and disease control rates(CR + PR + stable disease) were 95.3%, 92.1%, and 85.9% at 2, 4, and 6 months posttreatment, respectively. Multivariate logistic regression analysis showed that nodule number >3, high BCLC stage, no vascular leak, and previous conventional TACE treatment were associated with poor ORR (P < 0.05). Postoperation, liver function showed transient changes. Postoperative complications were tolerated and relieved by symptomatic treatment. The average interval of TACE before D TACE was 43 days, compared with 70 days for average interval of DEB TACE. The average hospital stay was 1.87 days. CONCLUSION: DEB TACE has improved short term efficacy and lower incidence of complications in primary HCC and prolongs the interval of TACE. It significantly increases the ORR, especially in patients with no extra hepatic metastasis pretreatment. DEB usage actually improves treatment efficacy and provides more benefits to patients. KEY WORDS: Drug-loaded bead-transcatheter arterial chemoembolization, hepatocellular carcinoma, microsphere embolization.