Effect of acute alcohol consumption on blunt bowel mesenteric injury: a retrospective analysis.

BACKGROUND: The effect of alcohol consumption on trauma remains controversial. The effects of alcohol on hemorrhage and peritonitis after blunt abdominal trauma have rarely been discussed. This study aimed to explore the effects of acute alcohol intoxication on the clinical characteristics, injury patterns, and outcomes in a surgical blunt bowel mesenteric injury (BBMI) cohort. METHODS: A retrospective data analysis was performed using trauma cases of patients who had been tested for alcohol and had surgically proven BBMI from a Trauma Registry System from 2009 to 2021. Patients were grouped according to their positive blood alcohol concentration (BAC; >0.5% vs. no BAC; less than 0.5% no BAC) upon arrival at the emergency department (ED). The injury characteristics, physiological parameters, and outcomes with respect to post-injury complications and mortality were assessed. RESULTS: In total, 142 patients with surgical BBMI were included. Of these, 116 and 26 patients were assigned to the BAC-negative and BAC-positive groups, respectively. The overall injury severity, injury pattern, and age were comparable between the groups. The patients in the BAC-positive group had a significantly lower systolic blood pressure (99 mmHg vs. 119 mmHg; p = 0.046), worse shock index (0.96 vs. 0.82; p = 0.048), and lower percentage and number of packed red blood cells transfused (34.6% vs. 57.8%; p = 0.032 and 0 U vs. 2 U; p = 0.031) than those in the BAC-negative group. Additionally, although not statistically significant, patients in the BAC-positive group had lower leukocyte counts (9,700 cells/mm3 vs. 11,600 cells/mm3; p = 0.165 ) at the ED. However, significantly reduced percentages of leukocytes ≥ 12,000 cells/mm3 (26.9% vs. 48.3%; p = 0.048) and ≥ 12,000 or ≤ 4,000 cells/mm3 (26.9% vs. 50.9%; p = 0.027) were observed in the BAC-positive group at the ED. Furthermore, the 30-day mortality rate did not show statistically significant differences, and there was a higher incidence of bowel-related mortality in the BAC-positive group (11.5% vs. 1.7%, p = 0.043). CONCLUSIONS: For patients with BBMI arriving alive to the hospital, acute alcohol consumption was associated with significantly worse hemodynamic parameters, interfered inflammation status, and higher bowel related mortality rate.

MSNet-4mC: learning effective multi-scale representations for identifying DNA N4-methylcytosine sites.

MOTIVATION: N4-methylcytosine (4mC) is an essential kind of epigenetic modification that regulates a wide range of biological processes. However, experimental methods for detecting 4mC sites are time-consuming and labor-intensive. As an alternative, computational methods that are capable of automatically identifying 4mC with data analysis techniques become a reasonable option. A major challenge is how to develop effective methods to fully exploit the complex interactions within the DNA sequences to improve the predictive capability. RESULTS: In this work, we propose MSNet-4mC, a lightweight neural network building upon convolutional operations with multi-scale receptive fields to perceive cross-element relationships over both short and long ranges of given DNA sequences. With strong imbalances in the number of candidates in different species in mind, we compute and apply class weights in the cross-entropy loss to balance the training process. Extensive benchmarking experiments show that our method achieves a significant performance improvement and outperforms other state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The source code and models are freely available for download at https://github.com/LIU-CT/MSNet-4mC, implemented in Python and supported on Linux and Windows. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A novel, ultrafast, ultrasensitive diagnosis platform for the detection of SARS-COV-2 using restriction endonuclease-mediated reverse transcription multiple cross displacement amplification.

Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Though many methods have been used for detecting SARS-COV-2, development of an ultrafast and highly sensitive detection strategy to screen and/or diagnose suspected cases in the population, especially early-stage patients with low viral load, is significant for the prevention and treatment of COVID-19. In this study, a novel restriction endonuclease-mediated reverse transcription multiple cross displacement amplification (MCDA) combined with real-time fluorescence analysis (rRT-MCDA) was successfully established and performed to diagnose COVID-19 infection (COVID-19 rRT-MCDA). Two sets of specific SARS-COV-2 rRT-MCDA primers targeting opening reading frame 1a/b (ORF1ab) and nucleoprotein (NP) genes were designed and modified according to the reaction mechanism. The SARS-COV-2 rRT-MCDA test was optimized and evaluated using various pathogens and clinical samples. The optimal reaction condition of SARS-COV-2 rRT-MCDA assay was 65°C for 36 min. The SARS-COV-2 rRT-MCDA limit of detection (LoD) was 6.8 copies per reaction. Meanwhile, the specificity of SARS-COV-2 rRT-MCDA assay was 100%, and there was no cross-reaction with nucleic acids of other pathogens. In addition, the whole detection process of SARS-COV-2 rRT-MCDA, containing the RNA template processing (15 min) and real-time amplification (36 min), can be accomplished within 1 h. The SARS-COV-2 rRT-MCDA test established in the current report is a novel, ultrafast, ultrasensitive, and highly specific detection method, which can be performed as a valuable screening and/or diagnostic tool for COVID-19 in clinical application.

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds.

The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.

Laser Acupuncture Analgesia on Postpartum Low Back Pain: A Prospective Randomized Controlled Study.

BACKGROUND: Unresolved postpartum LBP may affect women...s physical and psychological health. AIM: To investigate the analgesic effects of laser acupuncture therapy (LAT) for postpartum LBP. METHOD: Postpartum women with LBP were recruited and randomly assigned to the intervention group or the control group from November 2017 to July 2018. The participants in the intervention group received LAT and standard care. The participants in the control group received only standard care. The primary outcome was the Visual Analogue Scale for LBP. Secondary outcomes were limitation of daily activities and physical activity; perceived stress scale; and salivary cortisol values. RESULTS: In all, 106 participants were recruited and assigned to the intervention group or the control group. As compared with the control group, the participants in the LAT group had significantly lower intensity of LBP (mean ± SD: 1.21 ± 0.99 vs 3.25 ± 1.14; p < .001), limitations of daily activities (mean ± SD: 3.17 ± 2.09 vs 10.40 ± 4.72; p < .001) and physical activity (mean ± SD: 3.04 ± 2.17 vs 9.79 ± 4.71; p < .001), perceived stress (mean ± SD: 26.13 ± 3.97 vs 28.85 ± 4.26; p = .001), and salivary cortisol levels (mean ± SD: 0.194 ± 0.131 vs 0.280 ± 0.234; p = .02) post-intervention. CONCLUSIONS: For postpartum LBP, LAT combined with standard care had greater analgesic efficacy, lower perceived stress, lower limitations of daily activities and physical activity, and lower salivary cortisol levels than standard care alone.

Sensitive Detection of Sweat Cortisol Using an Organic Electrochemical Transistor Featuring Nanostructured Poly(3,4-Ethylenedioxythiophene) Derivatives in the Channel Layer.

In this study, we examined the influence of functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) nanostructures decorated on the channel layer of an organic electrochemical transistor (OECT) for the detection of sweat cortisol, an adrenocorticosteroid stress hormone. The OECT device featured a bilayer channel confined by a PEDOT:polystyrenesulfonate (PSS) underlayer and a nanostructure-decorated upper layer engineered from the monomers EDOT-COOH and EDOT-EG3 through template-free electrochemical polymerization. This molecular design allowed antibody conjugation using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysulfosuccinimide coupling through the carboxylic acid side chain, with EDOT-EG3 known to minimize nonspecific binding of biomolecules. We also engineered an OECT device having a channel area without any nanostructures to gain insight into the effect of the nanostructures on cortisol sensing. Our new nanostructure-embedded OECT device facilitated real-time detection of cortisol at concentrations ranging from 1 fg/mL to 1 µg/mL with a detection limit of 0.0088 fg/mL with good linearity (R2 = 0.9566), in addition to excellent selectivity toward cortisol among other structurally similar interfering compounds and high stability and reproducibility. With its rapid response for the detection of 100 ng/mL cortisol-spiked artificial sweat, this nanostructure-decorated OECT device has potential clinical practicality and utility in wearable sensors for future healthcare applications.

Pain Experiences and Coping Strategies in Rural Older Adults With Chronic Musculoskeletal Pain in Mountainous Areas of Taiwan.

BACKGROUND: Although rural communities are home to a higher proportion of older residents, they provide fewer healthcare services than do urban core communities. Chronic musculoskeletal (MSK) pain is often associated with reduced daily activity and quality of life in older adults, particularly those in rural areas. AIMS: This study investigated the pain experiences and coping strategies in rural older adults with MSK pain in Taiwan. METHODS: A structured questionnaire was used to collect data from rural older adults with chronic MSK pain in mountainous areas of Taiwan. RESULTS: In total, 55 rural older adults were enrolled in this study. The most common pain sites were the low back and knees. The main cause of pain was osteoarthritis. Three quarters of the participants suffered from moderate to severe chronic MSK pain on average. The results revealed that behavioral strategies were used more often than cognitive strategies. Regarding behavioral strategies, the most common non-pharmacologic and pharmacologic pain coping strategies were to rest and to take Chinese medicine, respectively. The most common cognitive strategy for pain coping was to talk to others. CONCLUSIONS: The findings suggested that pain management for chronic MSK pain in rural older adults was inadequate in mountainous areas of Taiwan. Most rural older adults used multiple coping strategies to deal with their pain, and behavioral strategies were favored over cognitive strategies.

Environmental factors and spatiotemporal distribution of Japanese encephalitis after vaccination campaign in Guizhou Province, China (2004-2016).

BACKGROUND: Although a vaccination campaign has been conducted since 2004, Japanese encephalitis (JE) is still a public health problem in Guizhou, one of the provinces with the highest incidence of JE in China. The aim of this study was to understand the spatiotemporal distribution of JE and its relationship with environmental factors in Guizhou Province in the post-vaccination era, 2004-2016. METHODS: We collected data on human JE cases in Guizhou Province from 2004 to 2016 from the national infectious disease reporting system. A Poisson regression model was used to analyze the relationship between JE occurrence and environmental factors amongst counties. RESULTS: Our results showed that the incidence and mortality of JE decreased after the initiation of vaccination. JE cases were mainly concentrated in preschool and school-age children and the number of cases in children over age 15 years was significantly decreased compared with the previous 10 years; the seasonality of JE before and after the use of vaccines was unchanged. JE incidence was positively associated with cultivated land and negatively associated with gross domestic product (GDP) per capita, vegetation coverage, and developed land. In areas with cultivated land coverage < 25%, vegetation coverage > 55%, and urban area coverage > 25%, the JE risk was lower. The highest JE incidence was among mid-level GDP areas and in moderately urbanized areas. CONCLUSIONS: This study assessed the relationship between incidence of JE and environmental factors in Guizhou Province. Our results highlight that the highest risk of JE transmission in the post-vaccination era is in mid-level developed areas.

Discovery and Biocatalytic Application of a PLP-Dependent Amino Acid γ-Substitution Enzyme That Catalyzes C-C Bond Formation.

Pyridoxal phosphate (PLP)-dependent enzymes can catalyze transformations of l-amino acids at α, ß, and γ positions. These enzymes are frequently involved in the biosynthesis of nonproteinogenic amino acids as building blocks of natural products and are attractive biocatalysts. Here, we report the discovery of a two-step enzymatic synthesis of (2S,6S)-6-methyl pipecolate 1, from the biosynthetic pathway of citrinadin. The key enzyme CndF is PLP-dependent and catalyzes the synthesis of (S)-2-amino-6-oxoheptanoate 3 that is in equilibrium with the cyclic Schiff base. The second enzyme CndE is a stereoselective imine reductase that gives 1. Biochemical characterization of CndF showed this enzyme performs γ-elimination of O-acetyl-l-homoserine to generate the vinylglycine ketimine, which is subjected to nucleophilic attack by acetoacetate to form the new Cγ-Cδ bond in 3 and complete the γ-substitution reaction. CndF displays promiscuity toward different ß-keto carboxylate and esters. With use of an Aspergillus strain expressing CndF and CndE, feeding various alkyl-ß-keto esters led to the biosynthesis of 6-substituted l-pipecolates. The discovery of CndF expands the repertoire of reactions that can be catalyzed by PLP-dependent enzymes.

Multiparameter Kinetic Analysis for Covalent Fragment Optimization by Using Quantitative Irreversible Tethering (qIT).

Chemical probes that covalently modify cysteine residues in a protein-specific manner are valuable tools for biological investigations. Covalent fragments are increasingly implemented as probe starting points, but the complex relationship between fragment structure and binding kinetics makes covalent fragment optimization uniquely challenging. We describe a new technique in covalent probe discovery that enables data-driven optimization of covalent fragment potency and selectivity. This platform extends beyond the existing repertoire of methods for identifying covalent fragment hits by facilitating rapid multiparameter kinetic analysis of covalent structure-activity relationships through the simultaneous determination of Ki , kinact and intrinsic reactivity. By applying this approach to develop novel probes against electrophile-sensitive kinases, we showcase the utility of the platform in hit identification and highlight how multiparameter kinetic analysis enabled a successful fragment-merging strategy.

Establishment and application of a multiple cross displacement amplification combined with nanoparticles-based biosensor method for the detection of Bordetella pertussis.

BACKGROUND: Bordetella pertussis is the causative agent of pertussis, a respiratory tract infectious disease. Efficient techniques for detection of B. pertussis isolates are important for clinical diagnosis. Multiple cross displacement amplification (MCDA), a novel isothermal amplification based molecular detection method, has been developed to overcome the technical drawback of the current methods in recent years. This aim of this study is to develop a MCDA with Nanoparticles-based Lateral Flow Biosensor (MCDA-LFB) for the detection of B. pertussis. RESULTS: A set of 10 primers based on the pertussis toxin (PT) promoter region sequence of B. pertussis was designed. The B. pertussis-MCDA-LFB assay was successfully established and optimized at 64 °C for reaction of 40 min. The detection limit was determined as 10 fg/reaction of pure DNA, and no cross-reactions to non-B. pertussis strains were observed, based on the specificity validation. The whole operation, ranging from template preparation to result reporting, could be completed within 70 min without requirement of costly equipment. The B. pertussis-MCDA-LFB in clinic sample detection yielded identical positive rates with traditional culture and showed higher sensitivity than conventional PCR. The results of MCDA-LFB are easier to read due to the usage of LFB. CONCLUSIONS: The isothermal amplification based MCDA-LFB established in the present study is a specific, sensitive, rapid and economical technique for the detection of B. pertussis.

Correction to: effect of acupressure on constipation in patients with advanced cancer.

The institutional review board number is incorrect, it should be No. 104-3133B.

A Narrative Review of Complementary Nutritional Supplements for Chemotherapy-induced Peripheral Neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common troublesome side effect and affects long-term activities of daily living. This neuropathic disorder is still difficult to treat with current clinical treatments. The aim of this study was to investigate and offer an updated perspective of complementary therapies for CIPN. METHODS: This review included current databases, including PubMed, Embase, the Cochrane Database, Google Scholar, and Ovid Medline, published up to May 2019 in the English language, to summarize the role of nutrient supplements in CIPN, based on evidence from both animal and clinical studies. RESULTS: A total of 58 studies were included in this review. There were 19 preclinical studies that reported mechanisms of effects and 31 clinical studies corroborated preclinical findings, including 22 randomized controlled trials and 3085 patients with CIPN. Interventions included vitamin E, vitamin B complex, glutamine, acetyl-L-carnitine, alpha lipoic acid, glutathione, omega-3 fatty acids, and calcium/magnesium (Ca2+/Mg2+). The administration of various nutrients remains inconsistent, and limited evidence of effective ones for treating CIPN is available. However, glutamine and omega-3 fatty acids present potential as treatment options for CIPN. The evidence on vitamin E and vitamin B complex is inconclusive, and some forms of vitamin B, such as B6 or B12, await confirmation of their potential to offer protection from CIPN. Less robust evidence was found for nutrients such as acetyl-L-carnitine, α-Lipoic acid, glutathione, and Ca2+/Mg2+ for CIPN. CONCLUSION: Nutritional therapists seem to recommend nutrient supplements as potential anti-inflammatory and neuroprotective agents for both the prevention and management of CIPN. An understanding of this evolving literature is useful in exploring these therapies with patients who are considering using them. However, their effects against CIPN are still controversial due to the undetermined neuropathic mechanisms of different antineoplastic agents and complex drug interactions. Further research on these agents is warranted.

Correlation between Glyoxal-Induced DNA Cross-Links and Hemoglobin Modifications in Human Blood Measured by Mass Spectrometry.

Glyoxal is an oxoaldehyde generated from the degradation of glucose-protein conjugates and from lipid peroxidation in foods and in vivo, and it is also present in the environment (e.g., cigarette smoke). The major endogenous source of glyoxal is glucose autoxidation, and the glyoxal concentrations in plasma are higher in diabetic patients than in nondiabetics. Glyoxal reacts with biomolecules forming covalently modified DNA and protein adducts. We previously developed sensitive and specific assays based on nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) for quantification of DNA cross-linked adducts (dG-gx-dC and dG-gx-dA) and for hemoglobin adducts derived from glyoxal. In this study, we isolated and analyzed both leukocyte DNA and hemoglobin from the blood of diabetic patients and compared the adduct levels with those from nondiabetic subjects using the modified assays. The results indicated that the extents of glyoxal-induced hemoglobin modifications on α-Lys-11, α-Arg-92, ß-Lys-17, and ß-Lys-66 were statistically higher in diabetic patients than nondiabetics and they correlated with HbA1c significantly. Moreover, the levels of dG-gx-dC in leukocyte DNA correlated positively with the extents of globin modification at α-Lys-11 and ß-Lys-17, while levels of dG-gx-dA correlated with those at α-Lys-11 and α-Arg-92 in nonsmoking subjects. Comparing the levels and the correlation coefficients of these hemoglobin and DNA adducts including or excluding smokers, it appears that smoking is not a major contributor to glyoxal-induced adduction of hemoglobin and leukocyte DNA. To the best of our knowledge, this is one of the few reports of positive correlation between DNA and protein adducts of the same compound (glyoxal) in the blood from the same subjects. Because of the high abundance of hemoglobin in blood, the results indicate that quantification of glyoxal-modified peptides in hemoglobin might serve as a dosimetry for glyoxal and a practical surrogate biomarker for assessing glyoxal-induced DNA damage and its prevention.

Effect of acupressure on constipation in patients with advanced cancer.

PURPOSE: Constipation is a common and distressing symptom for patients with advanced cancer. Few reports have focused on the symptoms of constipation in patients with advanced cancer. The aim of this study was to investigate the effect of a short-term acupressure intervention on patients with advanced cancer. METHODS: This study used a non-randomized, pre-post study design to assess the effect of acupressure intervention. A total of 30 patients with advanced cancer were recruited from the hospice unit of a medical center in southern Taiwan. In addition to routine care, patients in the intervention group received an 8-min acupressure treatment daily for 3 consecutive days. Three acupoints were used in this study: Zhongwan (CV12), Guanyuan (CV4), and Tianshu (ST25). Analysis of covariance was used to compare the differences in symptoms of constipation between the two groups, adjusted for baseline values. Effect sizes were calculated using partial eta squared (η2). RESULTS: Significant improvements in symptoms of constipation (partial η2 = 0.40, p < 0.001 for straining during defecation; partial η2 = 0.30, p = 0.002 for hard stools; partial η2 = 0.42, p < 0.001 for sensation of incomplete evacuation; and partial η2 = 0.29, p = 0.002 for sensation of anorectal obstruction), Bristol stool form scale scores (partial η2 = 0.40, p < 0.001), comfort levels during defecation (partial η2 = 0.82, p < 0.001), and colonic motility (partial η2 = 0.85, p < 0.001) were observed in patients receiving acupressure intervention compared with the controls. CONCLUSIONS: Findings from this study indicated that short-term acupressure was effective in alleviating symptoms of constipation among patients with advanced cancer. Further, randomized controlled trials are warranted to confirm the results.

Chiral Separation of Cytotoxic Flavan Derivatives from Daphne giraldii.

Twelve new flavan derivatives including four pairs of enantiomers, daphnegiralins A1-A4 (1) and daphnegiralins B1-B4 (2), and two pairs of epimers, daphnegiralins C1/C2 (3) and daphnegiralins D1/D2 (4), were isolated from the stem bark and roots of Daphne giraldii. Their structures were elucidated using spectroscopic analyses, computational approaches, and chemical methods. Separation of the enantiomeric mixtures (1a, 1b, 2a, and 2b) was achieved using chiral HPLC. The compounds were evaluated against a small panel of human cancer cell lines, and 1b-2, 2a, and 2b were cytotoxic against Hep3B human hepatoma cells.

Mitochondria targeted biomimetic platform for chemo/photodynamic combination therapy against osteosarcoma.

Clinical treatment for osteosarcoma (OS) is still lacking effective means, and no significant progress in OS treatment have been made in recent years. Single chemotherapy has serious side effects and can produce drug resistance easily, resulting poor therapeutic effect. As a modern and non-invasive treatment form, photodynamic therapy (PDT) is widely used to treat diverse cancers. Chemotherapy in combination with PDT is a particularly efficient antitumor method that could overcome the defects of monotherapies. Since mitochondria is a key subcellular organelle involved in cell apoptosis regulation, targeting tumor cells mitochondria for drug delivery has become an important entry point for anti-tumor therapy. Herein, we rationally designed a core-shell structured biomimetic nanoplatform, i.e., D@SLNP@OSM-IR780, to achieve tumor homologous targeting and mitochondria targeted drug release for chemotherapy combined with PDT against OS. Upon 808 nm laser irradiation, D@SLNP@OSM-IR780 exhibited excellent photo-cytotoxicity in vitro. The excellent targeting effect of D@SLNP@OSM-IR780 in tumor tissues produced a tumor inhibition rate of 98.9% in vivo. We further indicated that synergistic chemo-photodynamic effect induced by D@SLNP@OSM-IR780 could activate mitochondria-mediated apoptosis pathway, along with host immune response and potential photothermal effect. On the whole, D@SLNP@OSM-IR780 is revealed to be a promising platform for OS targeted combination therapeutics.

Serotype distribution, trend of multidrug resistance and prevalence of ß-lactamase resistance genes in human Salmonella isolates from clinical specimens in Guizhou, China.

Salmonella, one of the major causes of foodborne infections, can cause bacterial foodborne illness. We investigated the serotype distribution, multidrug resistance (MDR), and ß-lactamase resistance genes of human Salmonella isolates collected from clinical specimens in Guizhou, China, between 2013 and 2018. A total of 363 Salmonella isolates were collected from clinical specimens at 17 surveillance hospitals. Twenty-four serotypes were identified by sliding agglutination test. S. Enteritidis (33.9%), Salmonella 4,[5],12:i:- (24.0%), S. Typhimurium (16.3%), S. London (6.3%), and S. Derby (3.9%) were the top five serotypes. In 2018, the most common serotype changed from S. Enteritidis to S. Typhimurium. Among the 363 Salmonella isolates, 97.5% of isolates were resistant to at least one class of antimicrobial agents. For cephalosporins, ceftriaxone had the highest resistance rate of 10.5%, and cefepime and cefoxitin were 8.0% and 2.2%, respectively. Three hundred and one (82.9%) Salmonella isolates showed MDR. Salmonella 4,[5],12:i:- had the highest MDR rate with 94.2%, followed by S. London (91.3%) and S. Typhimurium (88.1%). Multidrug resistance rates of Salmonella isolates in Guizhou from 2013 to 2017 increased from 75.8% to 86.7%. Sixteen isolates (4.4%) showed extensive drug resistance. One hundred thirty-four antimicrobial resistance patterns were found. Two hundred and forty-one (66.4%) isolates carried at least one ß-lactamase resistance gene. The blaTEM gene (61.2%) was the most prevalent resistant gene in all Salmonella isolates, followed by the blaCTX-M gene (6.1%) and blaOXA-1 gene (4.1%). Our findings showed that the MDR rate of Salmonella isolates from Guizhou province increased year by year. Therefore, systematic and long-term surveillance on MDR Salmonella isolates from clinical patients should be further strengthened.

Assessment on compatibility and safety of labels for pharmaceutical packaging.

Although the secondary packing materials do not directly contact the finished drug products, compound migration may still happen between them. To ensure drug quality and safety, extractables and leachables of the packing materials should be analyzed. In this study, 2,6-di-tert-butyl-4-methylphenol (BHT) was first found in the labels for pharmaceutical packaging. For the identification of the compound, a strategy combining high performance liquid chromatography (HPLC), ultra-performance liquid chromatography-quadrupole time-of-flight mass (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy was utilized. Afterwards, a effective and sensitive HPLC method for quantification of BHT was developed and validated. Finally, a toxicological risk assessment of BHT was performed to ensure the safety of drugs.