The pharmacokinetics of vancomycin in patients with severe acute pancreatitis.

OBJECTIVE: The aim of this study was to evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP). METHODS: Sixty-seven patients with SAP were included. The FPIA method was used to measure vancomycin serum trough concentrations, and the pharmacokinetic parameters were calculated using the Bayesian estimator. Comparisons of mean values were analyzed using SPSS 11.0. RESULTS: The average daily dose of vancomycin was 15.0 ± 3.7 mg/kg (q 12 h). Sixty-seven trough concentrations were collected. Compared with the recommended standard vancomycin trough concentration (15 mg/L), SAP patients had significantly lower vancomycin trough concentrations (6.1 ± 3.0 mg/L; p < 0.0001) while the volume of distribution (Vd) and clearance (CL) of vancomycin were significantly increased. Multiple regression analysis revealed that vancomycin trough concentration was strongly correlated not only with age and albumin but also with the duration from SAP onset to vancomycin therapy (p < 0.0001). Stepwise regression analysis revealed that the duration was the most important variable for vancomycin trough concentration (r (2) = 0.456). The relationships between vancomycin trough concentrations and the duration were further evaluated after the 67 patients were stratified into two groups according to the duration from SAP onset to vancomycin therapeutic drug monitoring (TDM) within or over 4 weeks. Early group had much lower trough concentrations compared to late group, and the CL was also significantly increased in the early group. Of these 67 patients, 24 patients made vancomycin dosage adjustment (increased to 18.5 ± 3.9 mg/kg, q 12 h) and the average trough concentrations increased to 12.6 ± 3.8 mg/L. CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in SAP patients. Higher dosage regimens are needed to ensure the clinical effect.

Limited Sampling Strategy for the Estimation of Tacrolimus Area Under the Concentration-Time Curve in Chinese Adult Liver Transplant Patients.

OBJECTIVES: Limited sampling strategies (LSS) have been proposed as an alternative method for estimating area under concentration-time curve (AUC) of immunosuppressive agent tacrolimus (TAC). In this study, we aimed to develop the LSS models for predicting AUC of TAC in Chinese liver transplant patients. METHODS: Twenty-eight adult liver transplant patients receiving immunosuppressive regimen including TAC were enrolled. A total of 47 pharmacokinetic profiles were obtained after 1 or 3 weeks therapy. TAC concentrations were determined before dose (0 h) and at 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 h after dosing by LC-MS/MS assay. Optimal subset regression analysis was used to establish the models for estimating TAC AUC0-12. Prediction error (PE) and absolute PE were calculated. The agreement between predicted and measured AUC0-12 was investigated by Bland-Altman analysis. The obtained models were validated by bootstrap analysis. The prediction performance among various CYP3A5 and ABCB1 genotypes was compared. The models selected from previous published studies were also validated using our data. RESULTS: Twenty-eight models including 1, 2, 3 and 4 blood time points sampling were established (r2 = 0.653-0.979). The best model for prediction of TAC AUC0-12 was 0.81 + 1.73C1 + 1.32C2 + 3.87C4 + 3.75C8 (r2 = 0.979). Forty profiles (85.1%) had estimated TAC AUC0-12 within ±15% of observed TAC AUC0-12. Model with C0-C2 (r2 = 0.880) can be used for outpatients who need monitoring to be carried out in a short period. We also found that ABCB1 genotype may be a reason of variation in the prediction performance. There was good correlation between predicted and measured AUC0-12 (r2 = 0.880-0.928) by using models from previous studies with sample collected within 4 h post dose. CONCLUSION: The LSS is an effective approach for estimation of full TAC AUC0-12 in Chinese liver transplant patients.

Pre-Treatment Serum C-Reactive Protein Level Is An Independent Risk Factor for Development of Nephrotoxicity in Patients Receiving High-Dose Vancomycin.

High-dose vancomycin treatment increases the likelihood of vancomycin-related nephrotoxicity. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. In this study, we evaluated the pre-treatment serum CRP level as a risk factor of the development of nephrotoxicity in patients receiving high total daily doses (>2.5 g) of vancomycin. Data extracted from medical records for 174 patients who received total daily doses of >2.5 g of intravenous vancomycin for a minimum of 48 h and had their serum CRP level and erythrocyte sedimentation rate tested within 24 h before vancomycin treatment were subject to final analyses. Univariate analyses showed that patients who developed nephrotoxicity during vancomycin treatment had significantly higher median vancomycin serum concentration, duration of vancomycin treatment, and the serum CRP level within 24 h before vancomycin treatment than the non-nephrotoxicity group. Multivariate logistic regression analysis showed that after adjustment for potential confounders, median vancomycin serum concentration, duration of treatment, serum CRP level within 24 h before vancomycin treatment, and nephrotoxic medication were found significantly associated with the development of nephrotoxicity. This was confirmed by multivariate hazard ratio analysis after adjustment for potential confounders. In conclusion, this study provides the first evidence supporting the fact that the serum CRP level within 24 h before vancomycin treatment is an independent risk factor for the development of nephrotoxicity in patients receiving total daily doses of >2.5 g of vancomycin. Therefore, the serum CRP level within 24 h before vancomycin treatment could be a potential biomarker or prognostic factor for the development of vancomycin nephrotoxicity.

[Prognostic value of Picco monitoring combined with plasma microRNA-150 detection in septic shock patients].

OBJECTIVE: To assess the prognostic value of pulse indicator continuous cardiac output (Picco) monitoring combined with plasma microRNA-150 detection in septic shock patients. METHODS: Clinical data of 48 patients with septic shock admitted in General Intensive Care Unit (GICU), Shanghai First People's Hospital Songjiang Branch Affiliated to Shanghai Jiaotong University from August 2012 to August 2014 were analyzed retrospectively. The plasma levels of microRNA-150 in 48 patients at admission were assayed by qRT-PCR; and Picco monitoring was performed to record hemodynamic changes. The correlation of microRNA-150 or Picco parameters with prognosis of patients was assessed by univariate analysis and multivariate logistic analysis. Spearman correlation test showed the relationship between microRNA-150 and Picco parameters. Finally, the clinical value of combining microRNA-150 with Picco monitoring to predict the outcome of septic shock patients was analyzed by ROC curves. RESULTS: Twenty-three patients survived and 25 died in 28 d after admission in GICU. Compared with survival patients, microRNA-150 was significantly lower in fatal patients (t=-10.32, P<0.05). Univariate analysis showed that low microRNA-150 level was a risk factor for poor prognosis(OR=2.176,95% CI:1.121-4.223, P<0.05). Compared with fatal cases, the cardiac index of survival patients was higher, while EVLWI and PVPI were lower. MicroRNA-150 level was positively correlated with cardiac index (r=0.712, P<0.05), negatively correlated with EVLWI and PVPI (r=-0.622 and-0.689, both P<0.05). ROC curves showed a satisfactory diagnostic efficiency of combining microRNA-150 with Picco monitoring. CONCLUSION: Lower microRNA-150 may indicate a poor prognosis, and Picco monitoring combined with microRNA 150 detection may improve the prognostic efficiency in septic shock patients.

ChatGPT's innovative application in blood morphology recognition.

BACKGROUND: Recently, the rapid advancement in generative artificial intelligence (AI) technology, such as ChatGPT-4, has sparked discussions, particularly in image recognition. Accurate results are critical for hematological diagnosis, particularly for blood morphology identification. Despite advanced hematology analyzers, reliance on professional hematopathologists for manual identification remains in cases of abnormal or rare conditions, a process prone to human subjectivity and potential errors. Consequently, this study aimed to investigate the potential of ChatGPT-4 to assist with blood morphology identification. METHODS: We conducted a retrospective study using blood images obtained from the American Society of Hematology (ASH). These images comprised a range of normal and abnormal morphologies. Each sample was analyzed by expert technicians (control group) and classified using ChatGPT-4 (test group). RESULTS: Preliminary results showed that ChatGPT-4 could identify normal blood cells with an accuracy of 88%, exceeding the accuracy of identifying abnormal blood cells at a rate of 54%. Regarding identifying abnormal cells, the accuracy of ChatGPT-4 was slightly higher than that of the manual method, which was 49.5%. CONCLUSION: This study shows that although generative AI shows the potential for blood type identification, it has not yet reached the point where it can replace the professional judgment of medical staff. The results showed that ChatGPT-4 is excellent for identifying red blood cell morphology, particularly inclusion bodies. It can be used as an auxiliary tool for clinical diagnosis. However, the overall recognition accuracy must be further improved. Our study produced innovative results in this field, establishing a foundation for future studies and highlighting the potential of generative AI in aiding blood morphology recognition. Future research should focus on enhancing the effectiveness of AI to improve overall standards of medical care.

Comparative analysis of GPT-3.5 and GPT-4.0 in Taiwan's medical technologist certification: A study in artificial intelligence advancements.

BACKGROUND: This study examines the comparative effectiveness of GPT-3.5 and GPT-4.0, in the certification of medical technologists (MT) in Taiwan, exploring their adeptness in processing complex medical language and their contributory role in the educational and communicative aspects of professional healthcare training. METHODS: This study used GPT-3.5 and GPT-4.0 to test the medical laboratory technician professional college entrance examination questions. The questions in different fields, including six subjects, such as Clinical Physiology and Pathology, Hematology, and Blood Bank, among others were answered one-on-one using two generative pretrained transformer (GPT) versions, simulating the situations during exam preparation. RESULTS: A total of 480 questions were analyzed and the results showed that both versions of the GPT met the certification standards. Version 4.0 was better than version 3.5 for all subjects, particularly in Clinical Biochemistry (score = 96.25) and Microbiology (score = 91.25). Outstanding performance compared to version 3.5, which had an average score of 65.42 and a maximum score of 77.5. Overall, version 4.0, which was significantly better than version 3.5 in both median and average scores, reflects a significant improvement in professional knowledge processing capabilities. CONCLUSION: The GPT can provide valuable support for both the upstream and downstream processes of MT certification. Future research can further explore the application of GPT in different educational and certification contexts and improve the passing rate of medical personnel in the certification process. This study provides useful information for exploring the potential applications of GPT in certifying medical examiners. Furthermore, it provides new directions for future research in medical education.

Impaired immune response and barrier function in GSPD-1-deficient C. elegans infected with Klebsiella pneumoniae.

gspd-1-RNAi knockdown Caenorhabditis elegans was used as an immune-compromised model to investigate the role of G6PD in host-pathogen interactions. A shorted lifespan, increased bacterial burden and bacterial translocation were observed in gspd-1-knockdown C. elegans infected with Klebsiella pneumoniae (KP). RNAseq revealed that the innate immune pathway, including clc-1 and tsp-1, was affected by gspd-1 knockdown. qPCR confirmed that tight junction (zoo-1, clc-1) and immune-associated genes (tsp-1) were down-regulated in gspd-1-knockdown C. elegans and following infection with KP. The down-regulation of antimicrobial effector lysozymes, including lys-1, lys-2, lys-7, lys-8, ilys-2 and ilys-3, was found in gspd-1-knockdown C. elegans infected with KP. Deletion of clc-1, tsp-1, lys-7, and daf-2 in gspd-1-knockdown C. elegans infected with KP abolished the shorten lifespan seen in the Mock control. GSPD-1 deficiency in C. elegans resulted in bacterial accumulation and lethality, possibly due to a defective immune response. These findings indicate that GSPD-1 has a protective role in microbial defense in C. elegans by preventing bacterial colonization through bacterial clearance.

Evaluation of SLOG/TCI-III pediatric system on target control infusion of propofol.

BACKGROUND: The target-controlled infusion-III (SLOG/TCI-III) system was derived from a model set up by the local pediatric population for target control infusion of propofol. METHODS: The current study aimed at evaluating the difference between target concentrations of propofol and performance, which was measured using the SLOG/TCI-III system in children. Thirty children fulfilling the I-II criteria according to American Society of Anesthesiology were enrolled in the study. The target plasma concentration of propofol was fed into the SLOG/TCI-III system and compared with the measured concentrations of propofol. Blood samples were collected and analyzed by high performance liquid chromatography with fluorescence detector. The performance error (PE) was determined for each measured blood propofol concentration. The performances of the TCI-III system were determined by the median performance error (MDPE), the median absolute performance error (MDAPE), and Wobble (the median absolute deviation of each PE from the MDPE), respectively. RESULTS: Concentration against target concentration showed good linear correlation: concentration = 1.3428 target concentration - 0.2633 (r = 0.8667). The MDPE and MDAPE of the pediatric system were 10 and 22%, respectively, and the median value for Wobble was 24%. MDPE and MDAPE were less than 15 and 30%, respectively. CONCLUSIONS: The performance of TCI-III system seems to be in the accepted limits for clinical practice in children.

Investigation into molecular mechanisms and high-frequency core TCM for pulmonary fibrosis secondary to COVID-19 based on network pharmacology and data mining.

BACKGROUND: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. METHODS: The molecular mechanisms of PF secondary to COVID-19 were identified by mapping the COVID-19 differentially expressed gene and known targets associated with PF, protein-protein interactions network analysis, and enrichment pathway analysis; then the high-frequency core TCM targeting PF secondary to COVID-19 were identified by data mining and "Key targets related to PF secondary to COVID-19 - Ingredients" and "Key ingredients-key herbs" network analysis; and last we validated the interaction between the key ingredients and key targets by molecular docking. RESULTS: The molecular mechanisms of PF secondary to COVID-19 were mainly related to tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction pathway, and NF-κB signaling pathway. Among these, cytokines interleukin 6 (IL-6), TNF, and IL-1ß were identified as the key targets associated with PF secondary to COVID-19. The high-frequency core TCM targeting these key targets were identified, including ingredients of quercetin, epigallocatechin-3-gallate, emodin, triptolide, resveratrol, and herb of Polygonum cuspidatum. Finally, our results were validated by quercetin and resveratrol both well docked to IL-6, TNF, and IL-1ß protein, with the estimated docking energy <0 kcal/mol. CONCLUSIONS: This study identified the cytokines-related molecular mechanisms of PF secondary to COVID-19, and the high-frequency core TCM against PF by targeting IL-6, TNF, and IL-1ß. Which provides new ideas for the discovery of small molecular compounds with potential therapeutic effects on PF secondary to COVID-19.

Compound XiongShao Capsule ameliorates streptozotocin-induced diabetic peripheral neuropathy in rats via inhibiting apoptosis, oxidative - nitrosative stress and advanced glycation end products.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound XiongShao Capsule (CXSC), a traditional herb formula, has been approved for using to treat diabetic peripheral neuropathy (DPN) by the Shanghai Food and Drug Administration, with significant efficacy in clinic. AIM OF THE STUDY: This study aimed to investigate the multidimensional pharmacological mechanisms and synergism of CXSC against DPN in rats. METHODS: The quality analysis of CXSC was performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography. Rats with DPNinduced by streptozotocin/high-fat diet for 4 weeks were treated with CXSC at three doses (1.2 g/kg, 0.36 g/kg, and 0.12 g/kg), or epalrestat (15 mg/kg) daily for 8 weeks continuously. During the treatment period, body weight, serum glucose levels, and nerve function, including nerve conduction velocity (NCV), and mechanical and thermal hyperalgesia were tested and assessed every 4 weeks. In the 13th week, the histopathological examination in the sciatic nerve was performed using a transmission electron microscope. The expression of apoptosis-related proteins of BAX, BCL2, and caspase-3 in the sciatic nerve was examined using hematoxylin and eosin staining. The serum levels of advanced glycation end products (AGEs), oxidative-nitrosative stress biomarkers of superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured using a rat-specific ELISA kit. RESULTS: CXSC had no significant effect on body weight or serum glucose levels (P > 0.05), but it significantly improved mechanical hyperalgesia (F5,36 = 18.24, P < 0.0001), thermal hyperalgesia (F5,36 = 8.45, P < 0.0001), and NCV (motor NCV: F5,36 = 7.644, P < 0.0001, sensory NCV: F5,36 = 12.83, P < 0.0001). Besides, it maintained myelin and axonal structure integrity, downregulated the expression of apoptosis-related proteins in the sciatic nerve tissue, reduced AGEs and NOS levels, and enhanced antioxidant enzyme SOD activities in the serum. CONCLUSION: CXSC exerted neuroprotective effects against rats with DPN through multidimensional pharmacological mechanisms including antiapoptotic activity in the sciatic nerve and downregulation of the level of serum NOS, SOD and AGEs.

Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis.

BACKGROUND: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti-inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation. METHODS: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword "(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ", and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability. RESULTS: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins. CONCLUSION: Our results confirmed the anti-inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.

Reflex and habituation behavior of Caenorhabditis elegans assessed by a mechanical vibration system and image analysis.

BACKGROUND: The nematode Caenorhabditis elegans is an emerging invertebrate animal model for investigating neuronal functions in behavioral assays. C. elegans mechanosensation was characterized by the use of a constant mechanical stimulation transmitter followed by quantitative imaging. NEW METHOD: C. elegans reflex and habituation behaviors were characterized by mechanical vibration followed by image analysis. A custom-designed system consists of an aluminum alloy Petri dish holder frame coupled with a mechanical vibration buzzer delivering adjustable pulsed vibration to an agar plate. The basal and evoked movements of C. elegans were recorded by a microscopic digital camera followed by quantitative analysis using microscopic imaging software. RESULTS: Application of the platform in C. elegans was demonstrated with three proof-of-concept experiments: (1) Evaluation of the reflex response stimulated by tapping and mechanical vibration with a mechano-sensation defective mutant. (2) Comparison of the reflex response stimulated by mechanical vibration between wild type and aging mutants. (3) Assessment of the efficacy of the mechanical vibration system on long-term memory for habituation. COMPARISON WITH EXISTING METHODS: Conventional C. elegans mechanosensation techniques depend on stimulation either by manually touching a single animal or tapping the Petri dish followed by scoring via visual observation from the examiner. The mechanical vibration method has greater capacity compared to conventional methods which are labor-intensive, have low throughput and lack quantifiable parameters. CONCLUSIONS: The mechanical vibration system followed by image analysis is a convenient and integrated platform for investigatingC. elegans reflex and habituation in aging and neural behavioral assays.

Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression.

Daphne genkwa, a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid's cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor 'forkhead box protein M1' (FOXM1) and downstream FOXM1-regulated proteins related to epithelial-mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent.

Case report: Rapid improvement of crossed cerebellar diaschisis after intravascular laser irradiation of blood in a case of stroke.

RATIONALE: Crossed cerebellar diaschisis (CCD) is a poor prognostic factor after stroke because without immediate cerebral reperfusion no further improvements in the patient's condition can be achieved. We investigated the clinical effects of intravascular laser irradiation therapy (ILIB) on CCD and evaluated the therapeutic effect in the sub-acute post-stroke stage. PATIENT CONCERNS: The 77-year-old male with cerebral infarction in the territory of the right anterior cerebral artery only underwent conservative treatment including hydration and aspirin in the acute post-stroke stage. DIAGNOSIS: He was diagnosed as stroke based on the clinical presentations and imaging findings. INTERVENTION: Once the patient was in stable condition, he underwent a daily hour-long ILIB (He-Ne laser) for ten consecutive days during the sub-acute post-stroke stage. OUTCOMES: We used single-photon emission computed tomography (SPECT) before and after intravascular laser irradiation to detect changes in cerebral and cerebellar perfusion. Then, we compared the two images. CCD was detected using the first SPECT. After intervention by ILIB, the second SPECT showed greater perfusion in the affected cerebellar hemisphere. LESSONS: We found that ILIB helped eliminate CCD, which was previously shown to be an untreatable condition using any intervention during the sub-acute post-stroke stage. Stroke patients could therefore greatly benefit from ILIB.

Limited sampling strategy for predicting busulfan exposure in hematopoietic stem cell transplantation recipients.

Background Optimization of the area under the concentration-time curve (AUC) of busulfan, an essential component of conditioning regimens, improves the outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT). Traditional sampling methods for calculating AUC require multiple sampling. Objective To establish a limited sampling strategy for predicting the AUC0-12 of intravenous busulfan for Chinese adult patients prior to HSCT. Methods The pharmacokinetics of twice-daily intravenous busulfan was studied in forty-five Chinese adult patients. Limited sampling models were established by the multiple linear regression analysis. The prediction error (PE) and the absolute prediction error (APE) were calculated to evaluate predictive accuracy. The agreement between the predicted and actual AUC0-12 was investigated by the Bland-Altman analysis. The accuracy and robustness of the models was validated by the bootstrap analysis. Results The AUC0-12 values of the 1st and 7th doses of busulfan were 1491 ± 403.7 and 1908 ± 518.5 µmol L-1 min, respectively. The 2-sample model suggested that the predicted AUC0-12 of twice-daily intravenous busulfan could be calculated using the following equation: AUC0-12 = 40.017 + 0.955 × C3 + 1.088 × C6 with r2 = 0.919. The mean PE and APE of the model were 0.52 ± 7.67 and 6.32 ± 4.27%, respectively. Conclusion The 2-sample model is an effective and reliable approach to predict the AUC0-12 of twice-daily intravenous busulfan in Chinese adult patients.

Iron oxide nanopropellers prepared by a low-temperature solution approach.

The alpha-Fe(2)O(3) (hematite) nanopropellers were synthesized via a low-temperature solution-based method using FeCl(2) as a precursor in the presence of urea and glycine hydrochloride. The formation of alpha-Fe(2)O(3) nanopropellers is strongly depended on the addition of glycine hydrochloride, which serves as a pH modulator and affects the oxidation rate of Fe(2+). The structural evolution of the propeller-structured hematite was found to follow dissolution and recrystallization processes. For the structural conformation, each nanopropeller presents a hexagonal central column closed by six equivalent surfaces of {(-)1100} and the six arrays of the nanopropeller structure are a result of growth along +/- [(-)1100], +/- [(-)1010], and +/-[0(-)110]. Preliminary results show that the magnetic maghemite (gamma-Fe(2)O(3)) nanopropellers could also be prepared by a reduction and reoxidation process from the alpha-Fe(2)O(3) (hematite) nanopropeller precursors.

Transient receptor potential melastatin-2 and temperature participate in the process of CD38-regulated oxytocin secretion.

In recent studies, oxytocin showed potential for the treatment of mental diseases. CD38 is essential for oxytocin release, and hence plays a critical role in social behavior. CD38 catalyzes ß-NAD into cyclic ADP ribose (cADPR), which could elevate the intracellular Ca by Ca-permeable channels for oxytocin secretion. The temperature-sensitive cation channel, transient receptor potential melastatin-2 (TRPM2), is a cation-nonselective cation and has been shown to affect oxytocin indirectly. The aim of the present study was to verify the participation of temperature and TRPM2 in CD38-regulated oxytocin release. The crude membranes were prepared to isolate the nerve terminals from the posterior pituitary. At 34°C, 37°C, and 39°C, agonists (ß-NAD, ADPR, cADPR) and antagonists (8-Br-cADPR, 2-APB) were used to stimulate the nerve terminals. Oxytocin releases were investigated by enzyme-linked immunosorbent assay. In addition, the expression of TRPM2 and CD38 in the hypothalamus and pituitary was detected by western blotting and quantitative PCR. CD38 agonists (ß-NAD, cADPR) and antagonist (8-Br-cADPR) could increase or reduce the oxytocin release, respectively. TRPM2 agonist (ADPR) and antagonist (2-APB) alone could also regulate oxytocin release. Furthermore, temperature could increase agonist stimulation and attenuate the antagonist inhibition on oxytocin release. In addition, CD38 and TRPM2 were expressed in the hypothalamus and pituitary at both the mRNA and the protein level. TRPM2 in pituitary nerve terminals plays a role in oxytocin release. Temperature- enhanced oxytocin release by CD38 and TRPM2. TRPM2 might be involved in the process of CD38-regulated oxytocin release.

Clinical study of continuous micropump infusion of atropine and pralidoxime chloride for treatment of severe acute organophosphorus insecticide poisoning.

BACKGROUND: Our study sought to assess the effectiveness of a constant micropump infusion of atropine and pralidoxime chloride compared with repeated-bolus doses in patients with severe acute organophosphorus insecticide poisoning (AOPP). METHODS: A total of 60 patients with severe AOPP, defined as cholinergic crisis with respiratory failure or cerebral edema, were randomly divided into two groups of 30 patients each. In the experimental group, patients received a continuous micropump of atropine and pralidoxime chloride; in the control group, patients were given intermittent injections of atropine and pralidoxime chloride. Primary outcome measures were the dose of atropine required for atropinization, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at atropinization, time to atropinization and acetylcholinesterase (AchE) recovery time. Additionally, the case fatality rate was measured as a secondary outcome. RESULTS: Compared to patients in the control group, the time to atropinization, AchE recovery time, dose of atropine when atropinization occurred, and APACHE II score in the experimental group showed a statistically significant therapeutic effect (p < 0.05), and the case fatality rate of the experimental group was lower than that of the control group (p < 0.05). CONCLUSION: Continuous micropump of atropine and pralidoxime chloride combined is more effective than the use of repeated-bolus injection in the treatment of severe acute organophosphorus insecticide poisoning.

Antibody formation in pregnant women with maternal-neonatal human platelet antigen mismatch from a hospital in northern Taiwan.

Neonatal alloimmune thrombocytopenia (NAIT) is a clinical syndrome that resembles hemolytic disease of the newborn, affecting the platelets only. The thrombocytopenia results from the maternal alloantibodies reacting with specific human platelet antigens (HPAs) on the fetal platelets. Forty-four maternal plasma samples were screened for platelet alloantibodies using qualitative solid phase enzyme-linked immunosorbent assay (ELISA) commercial kit (LIFECODES Pakplus, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA), and both the maternal and the corresponding cord blood samples were genotyped (LIFECODES ThromboType, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA). HPA genotyping results correlated with the genetic frequencies in the Taiwan population. A total of 34 newborns (77.3%) had partial HPA genotyping mismatches with the corresponding mothers. The most common partial mismatches between mothers and neonates in HPA genotypes were 13 (29.5%) in both HPA-3b and HPA-15a, followed by 12 (27.3%) in HPA-15b, and 8 (18.2%) in HPA-3a. The frequencies of homozygotic mother with heterozygotic neonate were 15.9% in both HPA-3a and HPA-15b, 9.1% in HPA-15a, 6.8% in HPA-3b, and 2.3% in both HPA-2a and HPA-6a. In this study, maternal HPA antibodies were found in five samples, whereas HLA class I antibodies were found in seven maternal plasma samples from the antibody screen. The results from this study have demonstrated that HPA mismatch is not the main cause for the production of HPA alloantibodies.

[Significance of erythrocytes phosphatidylserine exposure on occurrence of anemia in sepsis].

OBJECTIVE: To investigate the role of phosphatidylserine (PS) exposure of erythrocytes in the development of anemia in sepsis patients. METHODS: A self-control study was conducted. Thirty sepsis patients admitted to intensive care unit (ICU) were enrolled. Peripheral venous blood was collected on 1 day and 7 days after ICU admission, and hemoglobin (Hb) concentration was examined routinely. A flow-cytometric assay based on Annexin V/ propidium iodide (Annexin V/PI) was used to measure the PS exposure of erythrocytes. The relationship between PS exposure and Hb concentration was analyzed. RESULTS: Hb concentrations in 30 sepsis patients at 7 days after ICU admission were significantly decreased compared with those of patients at 1 day (81.59±3.31 g/L vs. 121.90±3.34 g/L, t=8.570, P=0.000), but the percentage of PS exposure of erythrocytes was significantly higher [(17.19±1.35)% vs. (7.87±0.83)%, t=-6.557, P=0.000]. An inverse correlation was found between percentage of PS-positive RBCs and Hb concentration by Pearson analysis (r=-0.838, P=0.000). CONCLUSIONS: The percentage of PS exposure in erythrocytes is significantly increased in sepsis, and it might contribute to the development of anemia in sepsis patients during hospital stay. The more severe the anemia, the higher the PS in erythrocytes.