Evaluation of Analgesic Drug Therapy for Postoperative Pain Management in Cardiovascular Surgery.

Background: Cardiovascular surgery is usually associated with higher degree of postoperative pain that influences a patient's physical recovery. Multiple clinical measures have been taken to avoid overuse of opioid agents for postoperative pain management, which led to the development of clinical pathways for analgesic drug treatment using a multimodal approach. Objective: To evaluate the effectiveness and safety of a multimodal postoperative analgesic drug pathway (ADP) for pain management following cardiovascular surgery. Methods: This retrospective, controlled, nonrandomized study evaluated a postoperative ADP in patients undergoing cardiovascular surgery in a tertiary general hospital in Qingdao, China. Effectiveness and safety outcomes were compared before and after the implementation of the ADP. Outcome indicators included postoperative pain scores, consumption of opioids in analgesic pumps, and incidence of adverse events. Results: Patients who underwent cardiovascular surgery from September to November 2021 before the implementation of the ADP (n = 193) and from September to November 2022 after the implementation of the ADP (n = 218) were enrolled. Pain scores were reduced on day 1, 3, and 5 after surgery and the reduction was most significant in mild pain (P < .001). Opioids in analgesic pumps consumption was also significantly reduced and there was decreased incidence of adverse events such as nausea and vomiting (P = .026), respiratory inhibition (P = .027), and dizziness and headache (P = .028) in cardiovascular surgery patients after implementation of the ADP. Conclusions: Improved effectiveness and safety were observed following the implementation of the ADP. Multimodal analgesic ADP methodology can be effectively used for postoperative pain management in patients undergoing cardiovascular surgery.

Simultaneous quantification and pharmacokinetic evaluation of roflumilast and its N-oxide in cynomolgus monkey plasma by LC-MS/MS method.

Roflumilast (ROF), a nonsteroidal anti-inflammatory drug, has successfully been used to treat systemic and pulmonary inflammation associated with chronic obstructive pulmonary disease. To evaluate its pharmacokinetics in monkeys, a sensitive, rapid and reliable liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of ROF and its N-oxide metabolite (RNO). The mobile phase contained 0.1% formic acid aqueous solution (A) and 0.1% formic acid acetonitrile solution (B). All monkey plasma samples were pretreated using protein precipitation with methanol-acetonitrile (50:50, v/v) in 50 µl plasma samples. Chromatographic separation was performed with mass spectral acquisition performed in positive electrospray ionization, utilizing multiple reaction monitoring. This method was successfully applied to a pharmacokinetic study in cynomolgus monkeys. Following administration of a single oral dose of 1 mg/kg ROF in monkeys, pharmacokinetic data for ROF and RNO was reported for the first time. After oral administration, ROF was rapidly absorbed and metabolized to its metabolite RNO. The mean area under the curve value of RNO was ~13 times larger than that of ROF, suggesting that most ROF was metabolized to RNO in cynomolgus monkeys.

Slip Molding for Precision Fabrication of Microparts.

Microparts with precise sizes, custom shapes, and a wide selection of materials have various applications, including biomedical microelectromechanical systems (MEMS), drug delivery, single-cell studies, and tissue engineering. Janus microparts containing multiple components are also demonstrated for biomolecule analysis, cell-cell interaction studies, and self-assembly. Small-footprint, affordable, and rapid technologies to fabricate microparts with customized morphologies and a wide selection of materials are highly desired. This paper reports on a SlipChip-based microfluidic molding method to control the interface for the synthesis of microparts-on-demand (mPods) with fast and easy loading-slipping-solidification operations that do not require pumps, masks, or other auxiliary fluidic control instruments. This method is based on the relative movement of two microfluidic plates that are in close contact, and the size and shape of the microparts can be accurately controlled by the geometry of the microcavities imprinted on the contacting surfaces of these microfluidic plates. To demonstrate the capability of this method, mPods of different sizes and various shapes are presented with photosensitive resin via a photopolymerization reaction. The synthesis of two-layer Janus microparts is also demonstrated by a slip overmolding method. This SlipChip-based molding method can offer new opportunities for producing customized microparts with great flexibility for a broad spectrum of applications.

Multistep SlipChip for the Generation of Serial Dilution Nanoliter Arrays and Hepatitis B Viral Load Quantification by Digital Loop Mediated Isothermal Amplification.

Serial dilution is a commonly used technique that generates a low-concentration working sample from a high-concentration stock solution and is used to set up screening conditions over a large dynamic range for biological study, optimization of reaction conditions, drug screening, etc. Creating an array of serial dilutions usually requires cumbersome manual pipetting steps or a robotic liquid handling system. Moreover, it is very challenging to set up an array of serial dilutions in nanoliter volumes in miniaturized assays. Here, a multistep SlipChip microfluidic device is presented for generating serial dilution nanoliter arrays in high throughput with a series of simple sliding motions. The dilution ratio can be precisely predetermined by the volumes of mother microwells and daughter microwells, and this paper demonstrates devices designed to have dilution ratios of 1:1, 1:2, and 1:4. Furthermore, an eight-step serial dilution SlipChip with a dilution ratio of 1:4 is applied for digital loop-mediated isothermal amplification (LAMP) across a large dynamic range and tested for hepatitis B viral load quantification with clinical samples. With 64 wells of each dilution and fewer than 600 wells in total, the serial dilution SlipChip can achieve a theoretical quantification dynamic range of 7 orders of magnitude.

Docetaxel prodrug self-assembled nanosystem: Synthesis, formulation and cytotoxicity.

Conventional drug delivery systems of docetaxel (DTX) are challenged with low drug loading efficiency and potential carriers-induced toxicity. In this work, a docetaxel prodrug self-assembled nanosystem was designed and synthesized by conjugating docetaxel with oleic acid (OA) exploring a thioether as the linker, which is redox-sensitive to the redox environment within tumor cells. Notably, the carrier-free nanomedicine which does not need any carrier has obviously high drug loading that reaches 58%. Moreover, the cytotoxicity of DTX-S-OA maintains an equal level with DTX. The novel prodrug conjugate therefore has a promising perspective as carrier-free nanomedicine for cancer therapy due to its high drug loading property, redox-sensitive release and long circulation mechanism.

Enhancing Drug Management, Cost Savings, and Staff Satisfaction in Anesthesiology: A Quality Improvement Project in a Chinese Tertiary Hospital.

INTRODUCTION: In alignment with China's national directive for improved drug management in anesthesiology, the Affiliated Hospital of Qingdao University initiated a quality improvement project, aiming to tackle the prevailing challenges of inefficiencies in drug administration, escalating drug costs, and the notable communication gap between pharmacists and anesthesiologists. METHODS: We employed a Plan-Do-Study-Act methodology to establish a pharmacy team and execute a multidimensional pharmaceutical intervention. The interventions included the formulation of standard procedures, guidelines and regulations, assistance from an information system (including automatic dispensing cabinets and prospective prescription review system), communication feedback (via WeChat groups), and education for anesthesiology staff. The intervention spanned from April to September 2023, focusing on optimizing medication management, achieving cost savings, and enhancing the satisfaction of anesthesia team members, with an additional observation from October to December 2023. RESULTS: Following the interventions, improvements were observed in drug management practices. These enhancements included increased compliance with accounting procedures, more rigorous registration of controlled substances, and more effective disposal of liquid residues. There was no adverse events related to high-alert medications or look-alike drug usage errors. The introduction of automatic dispensing cabinets and a prospective prescription review system markedly improved work efficiency. The utilization of a WeChat group facilitated effective communication about unreasonable prescriptions and drug-related issues. Among the 29,061 patients who underwent surgery both before and after the interventions, significant reductions were observed both in the drug proportion and the per capita drug costs (P = 0.03, P = 0.014, respectively). The per capita drug cost decreased by 20.82%, from ¥723.43 to ¥572.78, consistently remaining below ¥600 throughout the 9-month observation period. The per capita cost of monitoring drugs including dezocine, butorphanol, haemocoagulase agkistrodon, penehyclidine, and ulinastatin experienced a significant reduction (P < 0.05). Additionally, in the satisfaction questionnaires returned, a remarkable 94.44% of anesthesiology staff expressed high satisfaction with the comprehensive pharmaceutical interventions. CONCLUSION: The quality improvement project has yielded remarkable positive outcomes, serving as a model worthy of reference and replication in similar healthcare settings.

A novel semi-flexible coaxial nozzle based on fluid dynamics effects and its self-centering performance study.

Coaxial nozzles are widely used to produce fibers with core-shell structures. However, conventional coaxial nozzles cannot adjust the coaxiality of the inner and outer needles in real-time during the fiber production process, resulting in uneven fiber wall thickness and poor quality. Therefore, we proposed an innovative semi-flexible coaxial nozzle with a dynamic self-centering function. This new design addresses the challenge of ensuring the coaxiality of the inner and outer needles of the coaxial nozzle. First, based on the principles of fluid dynamics and fluid-structure interaction, a self-centering model for a coaxial nozzle is established. Second, the influence of external fluid velocity and inner needle elastic modulus on the centering time and coaxiality error is analyzed by finite element simulation. Finally, the self-centering performance of the coaxial nozzle is verified by observing the coaxial extrusion process online and measuring the wall thickness of the formed hollow fiber. The results showed that the coaxiality error increased with the increase of Young's modulus E and decreased with the increase of flow velocity. The centering time required for the inner needle to achieve force balance decreases with the increase of Young's modulus ( E ) and fluid velocity ( v f ). The nozzle exhibits significant self-centering performance, dynamically reducing the initial coaxiality error from 380 to 60 µm within 26 s. Additionally, it can mitigate the coaxiality error caused by manufacturing and assembly precision, effectively controlling them within 8 µm. Our research provides valuable references and solutions for addressing issues such as uneven fiber wall thickness caused by coaxiality errors.

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde.

A one-pot three-component synthesis of dihydropyrimidinones via a molecular iodine-catalyzed tandem reaction of simple readily available mono-substituted urea, alkylaldehyde, and arylaldehyde has been developed. The reaction proceeds with high chemo- and regioselectivity to give highly diverse dihydropyrimidinones in reasonable yields under mild reaction conditions. Moreover, the first catalytic enantioselective version of this reaction was also realized by using chiral spirocyclic SPINOL-phosphoric acids.

Anti-inflammatory Mechanism of Action of Benzoylmesaconine in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Background: Benzoylmesaconine (BMA), the most abundant monoester alkaloid in Aconitum plants, has some biological activities and is a potential therapeutic agent for inflammation-related diseases. However, the potential anti-inflammatory mechanisms of BMA have not been clarified. Purpose: This study aimed to investigate the underlying molecular mechanisms of the anti-inflammatory action of this compound using lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Methods: The release of pro-inflammatory cytokines and mediators were detected by nitric oxide (NO) assays, reactive oxygen species (ROS) assays, and enzyme-linked immunosorbent assays (ELISA) in LPS-activated RAW264.7 macrophage cells. Quantitative real-time PCR was used to measure the gene expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cell viability was determined using a cell counting kit-8 (CCK-8) assay. The expression of iNOS, COX-2, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB)-related proteins were detected by western blot, and nuclear translocation of p65 was observed by immunofluorescence. Results: BMA significantly decreased the production of IL-1ß, IL-6, TNF-α, PGE2, NO, and ROS and inhibited the protein and mRNA levels of COX-2 and iNOS in LPS-activated RAW264.7 macrophages. Moreover, LPS-induced phosphorylation of IκBα, JNK, p38, and ERK; degradation of IκBα; and nuclear translocation of p65 were significantly suppressed by BMA treatment. Conclusion: These findings demonstrate that the anti-inflammatory effect of BMA was through the suppression of the NF-κB and MAPK signaling pathways and that it may be a therapeutic agent targeting specific signal transduction events required for inflammation-related diseases.

N6-methyladenosine methylation-related genes YTHDF2, METTL3, and ZC3H13 predict the prognosis of hepatocellular carcinoma patients.

Background: Hepatocellular carcinoma (HCC) is a common primary malignant tumor and cause of cancer-related death in humans. Increasing evidence indicates that an imbalance in N6-methyladenosine (m6A) methylation is strongly linked to the occurrence and development of cancer. We used comprehensive bioinformatics to establish a potential prognostic model of HCC based on m6A methylation-related genes. And case analyses were used to verify the results. Methods: The clinical data and gene expressions were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The prognostic value of m6A methylation-related genes in HCC patients and their relationship with the immune microenvironment were explored by comprehensive bioinformatics analyses. We also collected pathological specimens from 70 patients with HCC from the Department of Pathology, Affiliated Hospital of Qingdao University, and performed immunohistochemical staining on the specimens. We compared tumor specimens from 27 patients positive for METTL3, YTHDF2, and ZC3H13 staining with their adjacent normal tissues and against 27 patient specimens negative for METTL3, YTHDF2, and ZC3H13. The influence of METTL3, YTHDF2, and ZC3H13 on survival was analyzed, and the prognostic model for METTL3, YTHDF2, and ZC3H13 in HCC was verified by clinical data. Results: Most m6A methylation-related genes showed significantly different expressions between cancer and normal tissues. Three candidate m6A methylation-related genes (YTHDF2, METTL3, and ZC3H13) were significantly correlated with the overall survival (OS) of HCC patients. A Kaplan-Meier survival analysis indicated a worse prognosis of high-risk patients than that of low-risk patients. Immunological analysis showed that the high-risk group was more likely to have higher follicular helper T cell counts and lower resting memory CD4 T cell counts. The expression of YTHDF2, METTL3, and ZC3H13 was validated by other databases, including the Oncomine database, the Human Protein Atlas (HPA), and the Kaplan-Meier plotter. Conclusions: Our prognostic model based on m6A methylation-related genes effectively predicted the prognosis of HCC patients.

Α-pyrones and diketopiperazine derivatives from the marine-derived actinomycete Nocardiopsis dassonvillei HR10-5.

Three new α-pyrones, nocapyrones E-G (1-3), and three new diketopiperazine derivatives, nocazines A-C (4-6), together with a new oxazoline compound, nocazoline A (7), were isolated from the marine-derived actinomycete Nocardiopsis dassonvillei HR10-5. The new structures of 1-7 were determined by spectroscopic analysis, X-ray single-crystal diffraction, CD spectra, and modified Mosher and Marfey methods. Compounds 1-3 showed modest antimicrobial activity against Bacillus subtilis with MIC values of 26, 14, and 12 µM, respectively.

Single dose administration of L-carnitine improves antioxidant activities in healthy subjects.

L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 µmol/L. After single oral administration, the maximum plasma concentration (C(max)) and area under the curve (AUC(0-∞)) were 84.7 ± 25.2 µmol/L and 2,676.4 ± 708.3 µmol/L·h, respectively. The half-life and the time required to reach the C(max) was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.

Portable integrated digital PCR system for the point-of-care quantification of BK virus from urine samples.

This paper presents a portable integrated digital PCR (PI-dPCR) system with a self-partitioning SlipChip (sp-SlipChip) microfluidic device for the quantitative analysis of BK virus (BKV) viral load directly from raw urine samples. Digital PCR is an accurate nucleic acid quantification method with single-molecule sensitivity, but the complexity of the instrument and the limited integration of the operation workflow greatly limit its application in clinical diagnostics, especially point-of-care testing (PoCT). Our PI-dPCR system has a small footprint, is lightweight, and is fully integrated with the thermal control and fluorescence imaging modules. Unlike the traditional SlipChip device, which requires the precise overlapping of microfeatures on the contacting surfaces to establish the fluidic loading path, this sp-SlipChip device utilizes microchannels with alternating depth and width for fluidic manipulation. This system can quantify BKV directly from raw urine samples with a simple "sample-to-digital-result" operation workflow without complex nucleic acid extraction and purification steps. The current design of the system provides a dynamic range of 3.0 × 104 to 1.5 × 108 copies/mL of BKV DNA in clinical urine samples within 2 h. We tested the system for the quantification of BKV viral load in thirty archived urine samples from kidney transplantation recipients and twelve additional samples from six patients before and after the adjustment of immunosuppressive treatment. This integrated system provides a promising method for both the detection and monitoring of viral infection in a point-of-care setting.

Long noncoding RNA TUG1 facilitates cell ovarian cancer progression through targeting MiR-29b-3p/MDM2 axis.

Ovarian cancer (OC) is one of the most aggressive female cancers in the world. OC trends to be diagnosed at an advanced stage with abdominal metastasis. Our study explored the biological function and underlying mechanism of lncRNA on OC cell proliferation and migration. The expression of turine up-regulated gene 1 (TUG1) in human OC tissues and cell lines was measured by qRT-PCR. OC cell proliferation, viability, migration, and invasion were measured by MTT assays, colony formation assays, and transwell assays in vitro. Furthermore, the nude mice xenograft model was established to determine the effects of TUG1 in vivo. The relationship between TUG1 and miR-29b-3p, as well as miR-29b-3p and MDM2 were identified using the luciferase reporter assays. We showed that the expression of TUG1 and MDM2 were significantly increased, but the expression of miR-29b-3p was remarkably decreased in OC tissues and cell lines. Knockdown of TUG1 strongly inhibited the ability of cell proliferation, colony formation, migration, and invasion in vitro. The relationship between TUG1 and miR-29b-3p, or miR-29b-3p and MDM2 were predicted by StarBase and miRanda online software. Besides, miR-29b-3p reversed the positive effect of TUG1 on the OC cell proliferation, migration, and invasion through inhibiting MDM2 expression and increasing p53 phosphorylation level. Moreover, knockdown of TUG1 suppressed tumor growth in vivo. Taken all together, this study shows that TUG1 plays a crucial oncogenic role and facilitates cell proliferation, migration, and invasion in OC through regulating miR-29b-3p/MDM2 axis.

Self-partitioning SlipChip for slip-induced droplet formation and human papillomavirus viral load quantification with digital LAMP.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide, and persistent HPV infection can cause warts and even cancer. Nucleic acid analysis of HPV viral DNA can be very informative for the diagnosis and monitoring of HPV. Digital nucleic acid analysis, such as digital PCR and digital isothermal amplification, can provide sensitive detection and precise quantification of target nucleic acids, and its utility has been demonstrated in many biological research and medical diagnostic applications. A variety of methods have been developed for the generation of a large number of individual reaction partitions, a key requirement for digital nucleic acid analysis. However, an easily assembled and operated device for robust droplet formation without preprocessing devices, auxiliary instrumentation or control systems is still highly desired. In this paper, we present a self-partitioning SlipChip (sp-SlipChip) microfluidic device for the slip-induced generation of droplets to perform digital loop-mediated isothermal amplification (LAMP) for the detection and quantification of HPV DNA. In contrast to traditional SlipChip methods, which require the precise alignment of microfeatures, this sp-SlipChip utilized a design of "chain-of-pearls" continuous microfluidic channel that is independent of the overlapping of microfeatures on different plates to establish the fluidic path for reagent loading. Initiated by a simple slipping step, the aqueous solution can robustly self-partition into individual droplets by capillary pressure-driven flow. This advantage makes the sp-SlipChip very appealing for the point-of-care quantitative analysis of viral load. As a proof of concept, we performed digital LAMP on a sp-SlipChip to quantify human papillomaviruses (HPVs) 16 and 18 and tested this method with fifteen anonymous clinical samples.

Advances in Microfluidics-Based Technologies for Single Cell Culture.

Single cell culture has been considered one of the fundamental tools for single cell studies. Complex biological systems evolve from single cells, and the cells within biological systems are intrinsically heterogeneous. Therefore, culturing and understanding the behaviors of single cells are of great interest for both biological research and clinical studies. In recent years, advances in microfluidics-based technologies have demonstrated unprecedented capabilities for single cell studies, and they have made high-throughput single cell cultures possible. Microfluidic systems enable precise control of the microenvironment for single cell culture and monitoring of the behavior of single cells in real time. In addition, microfluidic devices can consist of upstream cell sorting and cell isolation, and they can also be seamlessly integrated with various downstream analysis methods. Therefore, microfluidic technologies can obtain data about the performance at the single-cell level, providing information that cannot be achieved by studying the ensemble behavior of cell colonies. In this review, the recent developments in droplet-based microfluidics, microwell-based microfluidics, trap-based microfluidics and SlipChip-based microfluidics for the study of single cell culture is focused on. Perspectives on future improvement regarding single cell culture and its related research opportunities are also provided.

Pharmacokinetic, metabolic stability, plasma protein binding and CYP450s inhibition/induction assessment studies of N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide as potential type 5 phosphodiesterase inhibitors.

N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide (NHPPC) is a new potential of type 5 phosphodiesterase (PDE5) inhibitors, synthesized from the avanafil analogue for the treatment of erectile dysfunction. The targets of this article were to assess plasma protein binding, liver microsomal metabolic stability, inhibition and induction on cytochrome P450 isozymes and the pharmacokinetics of NHPPC. Equilibrium dialysis technique was applied to determine Plasma protein binding (PPB) and NHPPC was evaluated in male Sprague-Dawley rats and Beagle dogs in vivo pharmacokinetic. The NHPPC was highly bound to plasma proteins in rats, dogs and human tested and the mean values for PPB rate were 96.2%, 99.6% and 99.4%, respectively. After in vitro liver microsomes incubated for 60 min, the percent remaining of NHPPC was 42.8%, 0.8% and 42.0% in rats, dogs and human, respectively. In vitro intrinsic clearance was found to be 0.0233, 0.1204 and 0.0214 mL/min/mg protein in rat, dog and human liver microsomes of NHPPC, respectively. NHPPC showed no significant inhibitory effects on major CYP450 enzymes, and had no significant induction potential on CYP1A2 and CYP3A4. Following oral administration in rats and dogs, t max was 6 and 0.5 h, respectively. The clearance for NHPPC was 1.19 and 1.46 L/h/kg in rats and dogs, respectively. And absolute bioavailability in rat and dog were approximately 34.5% and 53.1%, respectively. These results showed that NHPPC has a good development prospect.

Slip-driven microfluidic devices for nucleic acid analysis.

Slip-driven microfluidic devices can manipulate fluid by the relative movement of microfluidic plates that are in close contact. Since the demonstration of the first SlipChip device, many slip-driven microfluidic devices with different form factors have been developed, including SlipPAD, SlipDisc, sliding stripe, and volumetric bar chart chip. Slip-driven microfluidic devices can be fabricated from glass, quartz, polydimethylsiloxane, paper, and plastic with various fabrication methods: etching, casting, wax printing, laser cutting, micromilling, injection molding, etc. The slipping operation of the devices can be performed manually, by a micrometer with a base station, or autonomously, by a clockwork mechanism. A variety of readout methods other than fluorescence microscopy have been demonstrated, including both fluorescence detection and colorimetric detection by mobile phones, direct visual detection, and real-time fluorescence imaging. This review will focus on slip-driven microfluidic devices for nucleic acid analysis, including multiplex nucleic acid detection, digital nucleic acid quantification, real-time nucleic acid amplification, and sample-in-answer-out nucleic acid analysis. Slip-driven microfluidic devices present promising approaches for both life science research and clinical molecular diagnostics.

Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins.

Gastric cancer (GC) is one of the most malignant tumors, accounting for 10% of deaths caused by all cancers. Chemotherapy is often necessary for treatment of GC; the FOLFOX regimen is extensively applied. However, multidrug resistance (MDR) of GC cells prevents wider application of this treatment. Ubenimex, an inhibitor of CD13, is used as an immune adjuvant to treat hematological malignancies. Here, we demonstrate that CD13 expression positively correlates with MDR development in GC cells. Moreover, Ubenimex reverses the MDR of SGC7901/X and MKN45/X cells and enhances their sensitivity to FOLFOX, in part by decreasing CD13 expression, which is accompanied by downregulation of Bcl-xl, Bcl-2, and survivin expression; increased expression of Bax; and activation of the caspase-3-mediated apoptotic cascade. In addition, Ubenimex downregulates expression of membrane transport proteins, such as P-gp and MRP1, by inhibiting phosphorylation in the PI3K/AKT/mTOR pathway to increase intracellular accumulations of 5-fluorouracil and oxaliplatin, a process for which downregulation of CD13 expression is essential. Therefore, the present results reveal a previously uncharacterized function of CD13 in promoting MDR development in GC cells and suggest that Ubenimex is a candidate for reversing the MDR of GC cells.

[Effect of danhong injection on cerebral injury in patients undergoing coronary artery bypass graft operation with extracorporeal circulation].

OBJECTIVE: To investigate the effect and its possible mechanisms of Danhong Injection (DHI) on cerebral injury during coronary artery bypass graft (CABG) operation with hypothermic cardiopulmonary bypass (CPB). METHODS: Fifty patients went to CABG with CPB were randomly assigned equally to two groups, the control group and the tested group. DHI 1.5 mL/kg was pumped to where the tested group at the times of aortic pre-charging and unclamping respectively, but to the control group, equal volume of normal saline was given instead. Blood samples were taken from jugular bulb at different time points, i. e. before operation (T1, baseline), re-warming to 36 degrees C (T2 ), 30 min (T3 ) and 6 h (T4) after terminating CPB, for determination levels of superoxide dismutase (SOD) activity using xanthine oxidase method, malondialdehyde (MDA) concentration using thiobarbituric method, tumor necrosis factor alpha (TNF-alpha), as well as interleukin-6, -8 using radioimmunoassay and -10 (IL-6, IL-8 and IL-10) using ELISA. RESULTS: Level of SOD activity significantly decreased during (T2) and after CPB (T3 and T4) in the control group, as compared to the T1 (P < 0.01), but it was unchanged in the tested group; level of MDA increased during and after CPB in both groups (P < 0.01), but more significantly in the control group (P < 0.05), so comparison after CPB between the two groups showed a higher SOD and lower MDA level in the tested group. Plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 significantly increased in both groups after CPB (T3 and T4, P < 0.01) as compared to the T1, but the comparison between groups showed lower plasma TNF-alpha, IL-6 and IL-8 levels at T3 and T4, and higher IL-10 level at T4 in the test group (P < 0.01). All patients had stable life signs with no occurrence of adverse reaction. CONCLUSION: DHI has obvious protective effect on cerebral injury in patients undergoing CABG with CPB, the mechanisms may be associated with the actions of anti-oxidation, anti-inflammation and regulation on immune factors.