A two-front nutrient supply environment fuels small intestinal physiology through differential regulation of nutrient absorption and host defense.

The small intestine contains a two-front nutrient supply environment created by luminal dietary and microbial metabolites (enteral side) and systemic metabolites from the host (serosal side). Yet, it is unknown how each side contributes differentially to the small intestinal physiology. Here, we generated a comprehensive, high-resolution map of the small intestinal two-front nutrient supply environment. Using in vivo tracing of macronutrients and spatial metabolomics, we visualized the spatiotemporal dynamics and cell-type tropism in nutrient absorption and the region-specific metabolic heterogeneity within the villi. Specifically, glutamine from the enteral side fuels goblet cells to support mucus production, and the serosal side loosens the epithelial barrier by calibrating fungal metabolites. Disorganized feeding patterns, akin to the human lifestyle of skipping breakfast, increase the risk of metabolic diseases by inducing epithelial memory of lipid absorption. This study improves our understanding of how the small intestine is spatiotemporally regulated by its unique nutritional environment.

Gasdermin D-mediated metabolic crosstalk promotes tissue repair.

The establishment of an early pro-regenerative niche is crucial for tissue regeneration1,2. Gasdermin D (GSDMD)-dependent pyroptosis accounts for the release of inflammatory cytokines upon various insults3-5. However, little is known about its role in tissue regeneration followed by homeostatic maintenance. Here we show that macrophage GSDMD deficiency delays tissue recovery but has little effect on the local inflammatory milieu or the lytic pyroptosis process. Profiling of the metabolite secretome of hyperactivated macrophages revealed a non-canonical metabolite-secreting function of GSDMD. We further identified 11,12-epoxyeicosatrienoic acid (11,12-EET) as a bioactive, pro-healing oxylipin that is secreted from hyperactive macrophages in a GSDMD-dependent manner. Accumulation of 11,12-EET by direct supplementation or deletion of Ephx2, which encodes a 11,12-EET-hydrolytic enzyme, accelerated muscle regeneration. We further demonstrated that EPHX2 accumulated within aged muscle, and that consecutive 11,12-EET treatment rejuvenated aged muscle. Mechanistically, 11,12-EET amplifies fibroblast growth factor signalling by modulating liquid-liquid phase separation of fibroblast growth factors, thereby boosting the activation and proliferation of muscle stem cells. These data depict a GSDMD-guided metabolite crosstalk between macrophages and muscle stem cells that governs the repair process, which offers insights with therapeutic implications for the regeneration of injured or aged tissues.

Incidence and influencing factors of cephalosporin-induced anaphylaxis: a multicenter cross-sectional study. / é™è„‰æ³¨å°„å¤´å­¢èŒç´ ç±»è¯ç‰©æ‚£è€ è¿‡æ•ååº”å‘ç”ŸçŽ‡åŠå ¶å½±å“å› ç´ çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the incidence and influencing factors of allergic reactions to cephalosporins. METHODS: A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated. The influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression. RESULTS: A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67 ‰, the highest incidences of anaphylaxis occurred in ceftizoxime (4.27‰), followed by ceftriaxone (3.49‰) and cefotaxime (2.40‰). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75‰ vs. 1.63‰, RR=1.07, 95%CI:0.70-1.63, P> 0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/cm2 (RR=2.43, 95%CI: 1.23-4.82, P<0.01) and history of ß-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftriaxone (RR=3.74, 95%CI: 1.64-8.50, P<0.01). CONCLUSIONS: Lower BMI and history of ß-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions, and the routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.

Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method.

Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25−8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

Detecting response shift in health-related quality of life measurement among patients with hypertension using structural equation modeling.

BACKGROUND: Outcomes derived from longitudinal self-reported health-related quality of life measures can be confounded by response shift. This study was aimed to detect response shift among patients with hypertension attending a community-based disease management program. METHODS: 240 consecutive consulting or follow-up patients with diagnosed hypertension were recruited. The Short Form 36-item Health Survey was self-administered at 12 community health service stations at baseline and four weeks after attending the program. The 4-step structural equation modeling approach assessed response shift. RESULTS: Data from 203 (84.6%) patients were eligible for analyses (mean age 65.9 ± 10.8 years, 46.3% female). The results showed uniform recalibration of social functioning ([Formula: see text](1) = 22.98, P < 0.001), and non-uniform recalibration of role limitations due to physical problems ([Formula: see text](1) = 8.84, P = 0.003), and bodily pain ([Formula: see text](1) = 17.41, P < 0.001). The effects of response shift on social functioning were calculated as "small" (effect-size = 0.35), but changed the observed changes from improvement (effect-size = 0.25) to slight deterioration (effect-size = -0.10). After accounting for the response shift effect, the general physical health of participants was improved (effect-size = 0.37), while deterioration (effect-size = -0.21) in the general mental health was also found. CONCLUSIONS: Recalibration existed among patients with hypertension attending the disease management program. The interventions in the program might act as a catalyst that induced the response shift. We conclude that response shift should be considered in hypertension research with longitudinal health-related quality of life data.

pH-sensitive dual drug loaded janus nanoparticles by oral delivery for multimodal analgesia.

BACKGROUND: Based on the concept of "multimodal analgesia", a novel dual drug delivery system was designed to achieve synergistic analgesia between najanajaatra venom protein (αCT) and resveratrol (Res). In order to meet the joint loading of two drugs with different physicochemical properties without affecting each other, an oral Janus nanoparticle (JNP) with a unique cavity structure and synergistic drug delivery was constructed using an improved double emulsion solvent evaporation method, and combined with low-molecular-weight chitosan/sodium alginate and PLGA to achieve its pH-responsive. RESULTS: The synthesized αCT/Res-JNPs are homogeneous in shape, with a two-compartment structure, approximately 230 nm in size, and zeta potential of 23.6 mV. Drug release assayed in vitro show that JNP was stable in simulated gastric juice (pH = 1.2) but was released in phosphate buffer saline (pH = 7.4). After intragastric administration in rats, PK evaluation showed that αCT/Res-JNPs could significantly improve the oral bioavailability, and the simultaneous encapsulation of the two drugs had no significant interaction on PK parameters. An obvious synergistic analgesic effects of αCT/Res-JNPs was confirmed in a spinal cord injury and acute pain model. Confocal laser scanning microscopy and single-pass intestinal perfusion model provided strong evidence that αCT/Res-JNPs could pass through intestinal epithelial cells, and the endocytosis pathway was mainly involved in the mediation and pinocytosis of reticulin. The concentrations of αCT and Res from αCT/Res-JNP in lymphatic transport were only about 8.72% and 6.08% of their blood concentrations at 1 h, respectively, which indicated that lymphatic transport in the form of JNP has limited advantages in improving the oral bioavailability of Res and αCT. Cellular uptake efficiency at 4 h was about 10-15% in Caco-2 cell lines for αCT/Res-JNP, but was reduced to 7% in Caco-2/HT29-MTX co-culture models due to the hindrance by the mucus layers. Approximately 12-17% of αCT/Res-JNP were transported across Caco-2/HT29-MTX/Raji monolayers. The cumulative absorption of JNP in three cell models was higher than that of free drug. CONCLUSIONS: This study investigated the contribution of Janus nanoparticles in oral absorption, and provide a new perspective for oral administration and analgesic treatment of dual drug delivery system containing peptide drugs.

Cost-effectiveness of rivaroxaban versus warfarin in non-valvular atrial fibrillation patients with chronic kidney disease in China.

WHAT IS KNOWN AND OBJECTIVE: In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD. METHODS: A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to <50, 50 to <80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty. RESULTS AND DISCUSSION: The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to <50 mL/min), $9,758/QALY (50 to <80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of >80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates. WHAT IS NEW AND CONCLUSION: The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Orexin A alleviates neuroinflammation via OXR2/CaMKKß/AMPK signaling pathway after ICH in mice.

BACKGROUND: Orexins are two neuropeptides (orexin A, OXA; orexin B, OXB) secreted mainly from the lateral hypothalamus, which exert a wide range of physiological effects by activating two types of receptors (orexin receptor 1, OXR1; orexin receptor 2, OXR2). OXA has equal affinity for OXR1 and OXR2, whereas OXB binds preferentially to OXR2. OXA rapidly crosses the blood-brain barrier by simple diffusion. Many studies have reported OXA's protective effect on neurological diseases via regulating inflammatory response which is also a fundamental pathological process in intracerebral hemorrhage (ICH). However, neuroprotective mechanisms of OXA have not been explored in ICH. METHODS: ICH models were established using stereotactic injection of autologous arterial blood into the right basal ganglia of male CD-1 mice. Exogenous OXA was administered intranasally; CaMKKß inhibitor (STO-609), OXR1 antagonist (SB-334867), and OXR2 antagonist (JNJ-10397049) were administered intraperitoneally. Neurobehavioral tests, hematoma volume, and brain water content were evaluated after ICH. Western blot and ELISA were utilized to evaluate downstream mechanisms. RESULTS: OXA, OXR1, and OXR2 were expressed moderately in microglia and astrocytes and abundantly in neurons. Expression of OXA decreased whereas OXR1 and OXR2 increased after ICH. OXA treatment significantly improved not only short-term but also long-term neurofunctional outcomes and reduced brain edema in ipsilateral hemisphere. OXA administration upregulated p-CaMKKß, p-AMPK, and anti-inflammatory cytokines while downregulated p-NFκB and pro-inflammatory cytokines after ICH; this effect was reversed by STO-609 or JNJ-10397049 but not SB-334867. CONCLUSIONS: OXA improved neurofunctional outcomes and mitigated brain edema after ICH, possibly through alleviating neuroinflammation via OXR2/CaMKKß/AMPK pathway.

Association between the rate of third generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae and antibiotic consumption based on 143 Chinese tertiary hospitals data in 2014.

This study sought to discuss the correlation between the third-generation cephalosporins (3GC)-resistant Escherichia coli and Klebsiella pneumoniae and antibiotic consumption intensity from 143 Chinese tertiary hospitals in 2014. With a retrospective design, the correlation between antibiotic consumption and 3GC-resistant E. coli and K. pneumoniae were performed. 3GC-resistant E. coli was significantly correlated with the consumption of all antibiotics (r = 0.252, p < 0.01), ß-Lactams antibiotics (r = 0.313, p < 0.01), ß-Lactams excluding combinations with ß-lactamase inhibitors (r = 0.365, p < 0.01), cephalosporin (r = 0.398, p < 0.01), cephalosporins excluding combinations with ß-lactamase inhibitors (r = 0.374, p < 0.01), 3GC (r = 0.321, p < 0.01), and 3GC excluding combinations with ß-lactamase inhibitors (r = 0.343, p < 0.01). 3GC-resistant K. pneumoniae was significantly correlated with the consumption of all antibiotics (r = 0.200, p < 0.05), ß-Lactams antibiotics (r = 0.232, p < 0.01), cephalosporin (r = 0.215, p < 0.05), 3GC (r = 0.383, p < 0.01), 3GC excluding combinations with ß-lactamase inhibitors (r = 0.245, p < 0.01), and ß-lactam-ß-lactamase inhibitor combinations (r = 0.218, p < 0.05). There was a significant relationship between the antibiotic consumption and the rates of 3GC-resistant E. coli and K. pneumoniae. Clinicians should grasp the indication of antibiotics use to reduce the production of drug-resistant bacteria.

Severe cerebral edema induced by watershed shift after bypass in a patient with chronic steno-occlusive disease: a case report and short literature review.

BACKGROUND: Carotid occlusive disease is a type of progressive disease resulting in ischemic stroke. Extracranial-intracranial bypass surgery represents a valid therapeutic option when medical treatment does not make effects. The appearance of cerebral edema following bypass is common during acute stage. Additionally, there are many causes of mild cerebral edema, such as hemodynamic changes, venous congestion and others. However, severe edema involving large brain tissue, which presents as reversible aphasia and hemiplegia, remains to be elucidated. CASE PRESENTATION: A 55-year-old man was admitted to the neurosurgery department for repeated dizziness for over a year and sudden onset of syncope 1 month prior, and he was diagnosed with carotid occlusive disease. After surgical contraindications were excluded, dual bypass and encephalo-duro-myo-synangiosis were performed. Although blood pressure and fluid management were strictly under control promptly after surgery, massive cerebral edema involving the left anterior cerebral artery and middle cerebral artery territories occurred from the 6th day after surgery. Additionally, no discernible cerebral infarction or hemorrhage occurred. Moreover, the cerebral blood flow of the middle cerebral artery displayed an early decrease followed by delayed elevation on the left side. Without restricting the spreading of cerebral edema, life-threatening cerebral herniation could develop at any time. Mannitol and furosemide were administered for impending cerebral herniation. The amelioration of symptoms was noticed on the 16th day after surgery. The patient felt relief on the 21st day after surgery. Digital subtraction angiography performed on the 180th day after surgery demonstrated the patency of dual anastomosed vessels, and the patient recovered without any permanent neurological deficit. CONCLUSION: Based on changes in cerebral blood flow and reversible symptoms, the "watershed shift" phenomenon could explain such a severe deficit. However, this deficit was not the same as the classical presentation of the "watershed shift", which involves a moderate amount of brain tissue and presents significant increases in cerebral blood flow. In addition to the "watershed shift", a swollen temporal muscle may also participate in the progression of focal edema.

Association between the rate of fluoroquinolones-resistant gram-negative bacteria and antibiotic consumption from China based on 145 tertiary hospitals data in 2014.

BACKGROUND: The purpose of the study is to discuss the correlation between the resistance rate of gram negative bacteria to fluoroquinolones (FQ) and antibiotic consumption intensity of 145 China tertiary hospitals in 2014. METHODS: This retrospective study adopted national monitoring data from 2014. Each participating hospital required to report annual consumption of each antibiotic, and the resistance rate of gram negative bacteria to FQ. Then the correlation between antibiotic usage and fluoroquinolones -resistant (FQR) rate was consequently investigated. RESULTS: One hundred forty-five hospitals were included in the study, and the median antibiotic consumption intensity was 46.30 (23.93-115.39) defined daily dosages (DDDs) per 100 patient-days. Cephalosporins ranks first in the antibiotics consumption, followed by fluoroquinolones, penicillins, and carbapenems. Fluoroquinolones resistance rate varied from hospital to hospital. The correlation analysis showed significant relationship between the percentage of FQR Escherichia coli and the consumption of FQs (r = 0.308, p<0.01) and levofloxacin (r = 0.252, p<0.01). For FQR Klebsiella pneumoniae, not only FQs (r = 0.291, p<0.01) and levofloxacin (r = 0.260, p<0.01) use but also carbapenems (r = 0.242, p<0.01) and overall antibiotics (r = 0.247, p<0.01) use showed significant correlation. The resistant proportion of FQR Pseudomonas aeruginosa was observed to be correlated with the consumption of all antibiotics (r = 0.260, p<0.01), FQs (r = 0.319, p<0.01) and levofloxacin (r = 0.377, p<0.01). The percentage of levofloxacin-resistant Acinetobacter baumannii was significantly correlated with the consumption of all antibiotics (r = 0.282, p<0.01), third-generation cephalosporins excluding combinations with beta-lactamase inhibitors (r = 0.246, p<0.01), FQs (r = 0.254, p<0.01) and levofloxacin (r = 0.336, p<0.01). However, the correlation of the ciprofloxacin-resistant A. baumannii and the antibiotics consumption was not found. CONCLUSIONS: A strong correlation was demonstrated between the antibiotic consumption and the rates of FQR gram-negative bacteria. As unreasonable antibiotics usage remains crucial in the proceeding of resistant bacteria selection, our study could greatly promote the avoidance of unnecessary antibiotic usage.

Development and Validation of a Medication Selection Model Under Clinical Application of Renin-Angiotensin Inhibitor Combined with Calcium Channel Blocker for Hypertension Patients.

BACKGROUND This study evaluated the impact of clinical features and concomitant conditions on the clinical selection of different renin-angiotensin system (RAS) inhibitors in patients with hypertension, and built a renin-angiotensin inhibitors selection model (RAISM) to provide a reference for clinical decision making. MATERIAL AND METHODS We included 213 hypertensive patients in the study cohort; patients were divided into two groups: the angiotensin-converting enzyme inhibitor (ACEI) combined with calcium channel blocker (CCB) group (ACEI+CCB group) and the angiotensin receptor antagonist (ARB) combined with CCB group (ARB+CCB group). Basic demographic characteristics and concomitant conditions of the patients were compared. Single-factor and multi-factor analysis was performed by adopting logistic regression model. The RAISM was established by utilizing the nomograph technology. C-index and calibration curve were used to evaluate the model's efficacy. RESULTS In the study, 34.27% of the patients used ACEI+CCB and 65.73% of patients used ARB+CCB. The difference in age, body mass index (BMI), elderly patient, diabetes, renal dysfunction, and hyperlipidemia between the 2 groups determined medication selection. To be specific, compared to the group using ARB+CCB, the odds ratios and 95% confidence interval (CI) of the aforementioned factors for the ACEI+CCB group were 0.476 (0.319-0.711), 1.274 (1.001-1.622), 0.365 (0.180-0.743), 0.471 (0.203-1.092), 0.542 (0.268-1.094), and 0.270 (0.100-0.728), respectively; The C-index of RAISM acquired from the model construction parameters was 0.699, and the correction curve demonstrated that the model has good discriminative ability. CONCLUSIONS The outcome of our study suggests that independent discriminating factors that influence the clinical selection of different RAS inhibitors were elderly patient, renal insufficiency, and hyperlipidemia; and the RAISM constructed in this study has good predictability and clinical benefit.

Pharmacist-driven multidisciplinary initiative continuously improves postoperative nausea and vomiting in female patients undergoing abdominal surgery.

WHAT IS KNOWN AND OBJECTIVE: The incorrect or insufficient prophylaxis of postoperative nausea and vomiting (PONV) is common in practice. A clinical pharmacist-led guidance team (CPGT) was established and included in general surgery teams. OBJECTIVE: This study aimed to evaluate the effects of the CPGT on the improvement of PONV and prophylaxis administration. METHODS: A prospective before-after study was conducted on 156 female patients undergoing abdominal surgery at a Chinese tertiary teaching hospital from December 2016 to December 2017. A total of 82 patients were enrolled in the preintervention period, and 74 patients were included in the post-intervention period. The CPGT established the evidence-based criteria for prophylactic anti-emetic administration and conducted interventions, including a review of medical records, provision of feedback, educational outreach, and dedicated support. Primary outcomes included the incidence of PONV within 24 hours of surgery, administered number of prophylactic anti-emetics, and accuracy of the timing for prophylactic anti-emetics. Outcomes were analysed by logistic regression or multivariable linear regression. RESULTS AND DISCUSSION: After intervention, patients reported significantly less PONV (33.78% vs 56.10%; odds ratio [OR]: 0.29; numbers needed to treat [NNT]: 3.47), vomiting (29.73% vs 45.12%; OR: 0.42; NNT: 5.16) and nausea (31.08% vs 56.10%; OR: 0.24; NNT: 3.19) within 24 hours of surgery. The accuracy of the timing for prophylactic anti-emetics significantly increased (OR: 3.66; P: .003). Anaesthesiologists administered increased numbers of prophylactic anti-emetics (OR: 5.82; P < .001). The improvement of PONV did not decrease during the four-month period after intervention (P: .639). WHAT IS NEW AND CONCLUSION: The CPGT is a valuable service model to continuously improve PONV and optimize prophylaxis administration.

[Management of a colon cancer patient complicated with COVID-19].

OBJECTIVE: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

[Pharmaceutical care for severe and critically ill patients with COVID-19].

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.

Diagnostic performance of DWI for differentiating primary central nervous system lymphoma from glioblastoma: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) for differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma (GBM). MATERIALS AND METHODS: A thorough search of the databases including PubMed, EMBASE, and Cochrane Library was carried out and the data acquired were up to November 1, 2017. The quality of the studies involved was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies, revised version). Multiple analytic values including sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the summary receiver operating characteristic (SROC) curve were calculated and pooled for the statistical analysis. The subgroup analysis was also performed to explore the heterogeneity. RESULTS: Eight retrospective studies (461 patients with 461 lesions) were included. The pooled SEN, SPE, PLR, NLR, and DOR with 95% confidence interval (CI) were 0.82 [95% CI 0.70-0.90], 0.84 [95% CI 0.75-0.90], 4.96 [95% CI 3.20-7.69], 0.22 [95% CI 0.13-0.37], and 22.85 [95% CI 10.42-50.11], respectively. The area under the curve (AUC) given by SROC curve was 0.90 [95% CI 0.87-0.92]. The subgroup analysis indicated the slice thickness of the images (> 3 mm versus ≤ 3 mm) was a significant factor affecting the heterogeneity. No existence of significant publication bias was confirmed with Deeks' test. CONCLUSIONS: DWI showed moderate diagnostic performance for differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma (GBM). Moreover, it is of clinical significance using DWI combined with conventional MRI to differentiate PCNSL from GBM.

Combined delivery of angiopoietin-1 gene and simvastatin mediated by anti-intercellular adhesion molecule-1 antibody-conjugated ternary nanoparticles for acute lung injury therapy.

Effective treatment for acute lung injury (ALI) is in high demand. Lung-targeted ternary nanoparticles containing anti-intercellular adhesion molecule-1 (ICAM-1) antibody-conjugated simvastatin-loaded nanostructured lipid carrier (ICAM/NLC), protamine (Pro), and angiopoietin-1 (Ang-1) gene (ICAM-NLC/Pro/Ang) were developed for ALI therapy. The ternary nanoparticles with different weight ratios of ICAM-NLC to Ang-1 gene were prepared via charge interaction. The anti-ICAM-1 antibody-conjugated ternary nanoparticles exhibited higher cellular uptake and transfection efficiency (from 26.7% to 30.9%) in human vascular endothelial cell line EAhy926 than the non-targeted control. The largest size of ICAM-NLC/Pro/Ang (357.1 nm) was employed for further study, which significantly up-regulated in vitro and in vivo Ang-1 protein expression. In vivo i.v. administration of ICAM-NLC/Pro/Ang (357.1 nm) significantly attenuated pulmonary TNF-α and IL-6 levels, inflammatory cell infiltration, and led to positive histological improvements in lipopolysaccharide-induced ALI mice. Collectively, the ICAM-NLC/Pro/Ang that co-delivered simvastatin and Ang-1 gene may represent a potential treatment modality for ALI.

Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma.

BACKGROUD: Transarterial chemoembolization (TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanil-based patient controlled analgesia (PCA) could improve the pain management in patients receiving TACE for inoperable HCC. METHODS: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients' age, gender and pain scores, and divided the patients into the multimodal group (n = 42) and control group (n = 42). Patients in the multimodal group received 40 mg of parecoxib, 30 min before TACE, followed by 48 h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5 mg of dezocine during operation, and 100 mg of tramadol or equivalent intravenous opioid according to patient's complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient's satisfaction were all taken into consideration when evaluated. RESULTS: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12 h (all P < 0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group (31.0% vs. 59.5%). Patient's satisfaction in the multimodal group was also significantly higher than that in the control group (95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. CONCLUSION: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain control in HCC patients undergoing TACE.

Clinical pharmacist interventions on a Chinese neurology ward: a 2-year service evaluation.

A prospective observational study of clinical pharmacist interventions was conducted over a 2-year period from November 2012 to October 2014 to evaluate the clinical activity of pharmacists in the care they provide to patients and to promote safe and effective medication therapy by quantifying medicine-related interventions on a Chinese neurology ward. All pharmacist interventions made in the department of neurology were recorded, categorized, and assessed for potential patient harm if the intervention had not taken place. The quantity, outcomes, and potential severity of clinical pharmacists' interventions were recorded. 619 interventions were made in 385 patients over the 2-year observational period. The mean severity of potential harm assessment was 3.7 (1.12), range 0.8 - 7.0. 87 of the 619 interventions (14.0%) were classified as medication errors. The results of the clinical pharmacist intervention study demonstrated that pharmacists play an important role in the care of neurological patients by improving patient care and reducing clinical risk.

Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy.

Epilepsy is one of the most widespread serious neurological disorders, and an aetiological explanation has not been fully identified. In recent decades, a growing body of evidence has highlighted the influential role of autoimmune mechanisms in the progression of epilepsy. The hygiene hypothesis draws people's attention to the association between gut microbes and the onset of multiple immune disorders. It is also believed that, in addition to influencing digestive system function, symbiotic microbiota can bidirectionally and reversibly impact the programming of extraintestinal pathogenic immune responses during autoimmunity. Herein, we investigate the concept that the diversity of parasitifer sensitivity to commensal microbes and the specific constitution of the intestinal microbiota might impact host susceptibility to epilepsy through promotion of Th17 cell populations in the central nervous system (CNS).