Difference of Esophageal Motility and Reflux Characteristics in Patients with Gastroesophageal Reflux Disease (GERD) and Chronic Cough (CC) and the Impact of Standardized Drug Therapy.

This study aimed to explore the difference between esophageal motility and reflux characteristics in patients with gastroesophageal reflux disease (GERD) and chronic cough (CC) and the effect of standardized drug therapy. Eighty-four patients diagnosed with GERD in The First People's Hospital of Hangzhou from December 2020 to December 2022 were enrolled in this study. They were divided into an observation group (Obs group, patients with GERD + CC, n = 26 cases) and a control group (control group, patients with typical GERD, n = 58 cases). Reflux symptom integral questionnaire, cough symptom integral questionnaire, high-resolution esophageal manometry (HRM), and 24-hour esophageal pH/impedance monitoring were performed. The upper esophageal sphincter pressure at resting (UESP) and distal systolic score (DCI) in the Obs group were much lower. They exhibited differences with P < .05 than those in the control group. The total numbers of proximal reflux, proximal weak acid reflux, proximal non-acid reflux, weak acid reflux, and gas-liquid mixed reflux in the Obs group were more. They showed a difference with P < .05 than those in the control group. After a standard treatment, the reflux symptom score of patients with GERD + CC was greatly lower than those of patients with typical GERD (P < .05). Ineffective esophageal motility (IEM) was dominant in patients with GERD +CC. HRM and 24-hour pH/impedance monitoring can objectively evaluate the properties of esophageal motility and reflux, respectively, which had a guiding significance for individual patient treatment.

Efficacy of Black Gold, Delicate Pulse Light, Super Photon Skin Rejuvenation for Pigmented Dermatoses.

Context: Pigmented dermatoses are skin diseases characterized by pigmentation changes in the skin's surface due to abnormal melanocyte production. Photon-skin-rejuvenation technology can be effective for the management of facial pigmented dermatoses. Black Gold Delicate Pulse Light (DPL) Super Photon Skin Rejuvenation therapy is a new technology based on traditional photo rejuvenation. Objective: The study intended to evaluate the therapeutic efficacy of DPL therapy in the management of targeted pigmented skin diseases, such as melasma, solar lentigines, and postinflammatory hyperpigmentation. Design: The research team conducted a prospective cohort study. Setting: The study took place at Department of Dermatology, Affiliated Hospital of Shaoxing University, Shaoxing, China. Participants: Participants were 130 patients with facial pigmented dermatoses treated at the hospital between February 2021 and December 2021. Interventions: The research team assigned participants to one of two groups, with 65 participants in each group: (1) the control group, the intense pulsed light (IPL) group, who received IPL treatment, and (2) the intervention group, the DPL group, who received black gold DPL super photon skin rejuvenation. Both groups received the treatments once a month for 6 months. Outcome Measures: At baseline and postintervention for both groups, the research team: (1) collected 5 ml of fasting venous blood from participants and measured serum concentrations of melatonin (MEL), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) using enzyme-linked immunosorbent assay (ELISA); (2) assessed the degree of reduction of facial pigmentation using the Visia skin test and each participant's clinical results and calculated total efficacy; and (3) monitored and recorded adverse events. Results: Compared to the IPL group, the DPL group: (1) had greater symptom mitigation of the facial pigmented dermatosis, as evinced by significantly lower serum MEL (P = .001) and ET-1 (P = .020) concentrations and higher VEGF levels (P = .001); (2) for participants with freckles (P = .045), cafe-au-lait spots (P = .021), or post-acne hyperpigmentation (P = .029), had a significantly higher total efficacy; and (3) had a lower incidence of adverse events (P = .041). Conclusions: Black Gold DPL Super Photon Skin Rejuvenation offers a significantly higher safety profile and treatment efficacy for pigmented-skin diseases compared to IPL treatment. These promising results suggest potential for its use in clinical practice, but clinical adoption requires future trials.

Digital droplet immunoassay based on a microfluidic chip with magnetic beads for the detection of prostate-specific antigen.

Sensitive biomarker detection techniques are beneficial for both disease diagnosis and postoperative examinations. In this study, we report an integrated microfluidic chip designed for the immunodetection of prostate-specific antigens (PSAs). The microfluidic chip is based on the three-dimensional structure of quartz capillaries. The outlet channel extends to 1.8 cm, effectively facilitating the generation of uniform droplets ranging in size from 3 to 50 µm. Furthermore, we successfully immobilized the captured antibodies onto the surface of magnetic beads using an activator, and we constructed an immunosandwich complex by employing biotinylated antibodies. A key feature of this microfluidic chip is its integration of microfluidic droplet technology advantages, such as high-throughput parallelism, enzymatic signal amplification, and small droplet size. This integration results in an exceptionally sensitive PSA detection capability, with the detection limit reduced to 7.00 ± 0.62 pg/mL.

Applications of capillary electrophoresis in the fields of environmental, pharmaceutical, clinical, and food analysis (2019-2021).

So far, the potential of capillary electrophoresis in the application fields has been increasingly excavated due to the advantages of simple operation, short analysis time, high-resolution, less sample consumption, and low cost. This review examines the implementations and advancements of capillary electrophoresis in different application fields (environmental, pharmaceutical, clinical, and food analysis) covering the literature from 2019 to 2021. In addition, ultrasmall sample injection volume (nanoliter range) and short optical path lead to relatively low concentration sensitivity of the most frequently used ultraviolet-absorption spectrophotometric detection, so the pretreatment technology being developed has been gradually utilized to overcome this problem. Despite the review being focused on the development of capillary electrophoresis in the fields of environmental, pharmaceutical, clinical, and food analysis, the new sample pretreatment techniques of microextraction and enrichment fit excellently to capillary electrophoresis in recent three years are also described briefly.

Novel evidence for retinoic acid-induced G (Rig-G) as a tumor suppressor by activating p53 signaling pathway in lung cancer.

Lung cancer is one of most common malignancies worldwide. We have previously identified retinoic acid-induced gene G (Rig-G) as a tumor suppressor in not only acute promyelocytic leukemia, but also in other solid tumors. However, the clinical significance of Rig-G and the underlying mechanism(s) for its biological function in lung cancer remain largely unexplored. Herein, we first compared the expression of Rig-G between lung cancer (n = 138) and normal tissues (n = 23), from public-available data sets and our patient cohort. We further analyzed the correlation of Rig-G expression with key clinico-pathological features and survival outcomes in a multi-site clinical cohort of 300 lung cancer patients. Functional studies for Rig-G were performed in cell lines, and an animal model to support clinical findings. We found that Rig-G was frequently downregulated in lung cancer tissues and cell lines, and correlated with poor prognosis in lung cancer patients. Overexpression of Rig-G led to significantly reduced cell growth and suppressed migration in A549 and NCI-H1944 cells, accompanied by reduced epithelial-mesenchymal transition. Likewise, restoration of Rig-G in Lewis lung carcinoma cells permitted development of fewer cancer metastases versus controls in an animal model. Gene expression profiling results identified p53 pathway as a key downstream target of Rig-G, and p53 inhibition by pifithrin-α caused abrogation of tumor-suppressive effects of Rig-G in lung cancer. In conclusion, we, for the first time, have identified Rig-G as a novel and important tumor suppressor, which may serve as a potential therapeutic target for restoring p53 expression in lung cancer patients.

Traditional and new applications of the HCR in biosensing and biomedicine.

The hybridization chain reaction is a very popular isothermal nucleic acid amplification technology. A single-stranded DNA initiator triggers an alternate hybridization event between two hairpins forming a double helix polymer. Due to isothermal, enzyme-free and high amplification efficiency characteristics, the HCR is often used as a signal amplification technology for various biosensing and biomedicine fields. However, as an enzyme-free self-assembly reaction, it has some inevitable shortcomings of relatively slow kinetics, low cell internalization efficiency, weak biostability of DNA probes and uncontrollable reaction in these applications. More and more researchers use this reaction system to synthesize new materials. New materials can avoid these problems skillfully by virtue of their inherent biological characteristics, molecular recognition ability, sequence programmability and biocompatibility. Here, we summarized the traditional application of the HCR in biosensing and biomedicine in recent years, and also introduced its new application in the synthesis of new materials for biosensing and biomedicine. Finally, we summarized the development and challenges of the HCR in biosensing and biomedicine in recent years. We hope to give readers some enlightenment and help.

Rapid detection of carbamate pesticide residues using microchip electrophoresis combining amperometric detection.

The long-term consumption of food with pesticide residues has harmful effects on human health and the demand for pesticide detection technology tends to be miniaturized and instant. To this end, we demonstrated the first application of indirectly detecting two carbamate pesticides, metolcarb and carbaryl, by gold nanoparticle-modified indium tin oxide electrode in dual-channel microchip electrophoresis and amperometric detection (ME-AD) system. m-Cresol and α-naphthol were obtained after pesticide hydrolysis in alkaline solution, and then separated and detected by ME-AD. Parameters including the detection potential and running buffer concentration and pH were optimized to improve the detection sensitivity and separation efficiency. Under the optimal conditions, the two analytes were completely separated within 80 s. m-Cresol and α-naphthol presented a wide linear range from 1 to 100 µM, with limits of detection of 0.16 µM and 0.34 µM, respectively (S/N = 3). Moreover, the reliability of this system was demonstrated by analyzing metolcarb and carbaryl in spiked vegetable samples.

Combination of microfluidic chip and electrostatic atomization for the preparation of drug-loaded core-shell nanoparticles.

To overcome the shortcoming of drug-loaded nanoparticles, such as high initial burst release and wide size distribution, a novel manufacturing technique for core-shell structure nanoparticle was developed by combining microfluidic chip and electrohydrodynamic atomization. In this study, the mixture solution of the surfactant 1, 2- dipalmitoyl-sn-glycero-3-phosphoglycerol and the polymeric coating material polylactic-glycolic-acid was introduced into the outer microchannel of the microfluidic chip as the particle's shell. And the encapsulated drug paclitaxel was pumped into the inner microchannel as the core. Then, the particles with a nanoscale-size core-shell structure were generated by applying an electric field on the laminar flow which was formed in the microfluidic chip. Operation parameters, including working voltage, carrier material and surfactant concentration as well as liquid flow rates were optimized for nanoparticles generation. The properties of drug-loaded nanoparticles in terms of their particle size, zeta potential and encapsulation efficiency were investigated. Under the optimal experimental conditions, the particle size was approximately 145 nm and encapsulation efficiency reached 92%. Moreover, the drug release of these nanoparticles could be prolonged over a significant period for more than ten days. It can be expected that this innovative approach could provide a useful platform for drug-loaded core-shell nanoparticles developing.

Novel approaches for biomolecule immobilization in microscale systems.

Biomolecule-immobilized microscale systems present promising potential in the analysis field based on their reduced reagent consumption, improved analysis speed, automated processing, and high throughput. To increase the biomolecule binding capacity, improve the biomolecule activity and stability, enhance renewability, and develop easy-to-operate procedures, novel immobilization approaches have attracted tremendous attention recently. In this review, a variety of methods employed in preparing state-of-the-art DNA-, protein-, and polysaccharide-immobilized microscale systems are summarized. We focus on highlighting the merits of applying the click reaction, the nanomaterial-based strategy, encapsulation, layer-by-layer assembly, and the reversible immobilization strategy for improving the biomolecule-immobilized microscale system performance. Moreover, the utilization of innovative biomolecule-immobilized microscale systems for biosensing, affinity chromatography separation, bioreaction, and enantioseparation is also discussed.

Click chemistry at the microscale.

Click chemistry has attracted tremendous attention for the fabrication of novel microscale systems based on its high reaction efficiency, satisfactory versatility and simple processing. Meanwhile, microscale systems also provide desirable analytical platforms for click reaction study. Herein, we review the employment of click reactions for developing state-of-the-art microchip-based and capillary-based systems. The advantages of innovative off-stoichiometry thiol-ene (OSTE)-microchips, bio-functionalized microchips and monolithic microsystems for chemical and biological assays are highlighted. Moreover, the potential of microscale systems applied for click reaction investigation is indicated as well. This article presents an overview of the recent developments in the combination of microscale systems and click chemistry.

A multichannel microchip containing 16 chambers packed with antibody-functionalized beads for immunofluorescence assay.

A multichannel chip containing 16 microchambers was developed for fast and sensitive immunoassays. In each chamber, antibody-functionalized nonmagnetic beads were applied as the solid phase to capture target antigens. Four types of IgGs (human, rabbit, chicken, and mouse) could be detected simultaneously by our combining this microchip with a sandwich immunoassay technique. A three-layer chip structure was investigated for integration of multiple processes, including washing, immune reaction, and detection, in one microchip. Moreover, the proposed chip design could improve batch-to-batch repeatability and avoid interferences between different channels without the preparation of complex microvalves. The total operation time of this system was less than 30 min, with a desirable detection limit of 0.2 pg/mL. The results indicate that the microfluidic platform is promising for the immunoassay of multiple clinical biomarkers. Graphical abstract.

Novel Surface-Enhanced Raman Spectroscopy Techniques for DNA, Protein and Drug Detection.

Surface-enhanced Raman spectroscopy (SERS) is a vibrational spectroscopic technique in which the Raman scattering signal strength of molecules, absorbed by rough metals or the surface of nanoparticles, experiences an exponential growth (10³-106 times and even 1014-1015 times) because of electromagnetic or chemical enhancements. Nowadays, SERS has attracted tremendous attention in the field of analytical chemistry due to its specific advantages, including high selectivity, rich informative spectral properties, nondestructive testing, and the prominent multiplexing capabilities of Raman spectroscopy. In this review, we present the applications of state-of-the-art SERS for the detection of DNA, proteins and drugs. Moreover, we focus on highlighting the merits and mechanisms of achieving enhanced SERS signals for food safety and clinical treatment. The machine learning techniques, combined with SERS detection, are also indicated herein. This review concludes with recommendations for future studies on the development of SERS.

Immobilization of carbonic anhydrase on polyvinylidene fluoride membranes.

In recent years, the application of carbonic anhydrase (CA) in CO2 removal has attracted great interest. However, obtaining high enzyme recovery activity is difficult in existing immobilization techniques. In this work, water plasma-treated poly(vinylidene fluoride) (PVDF) membranes were modified via 3-aminopropyl triethoxy silane (KH550) or γ-(2, 3-epoxypropoxy) propyl trimethoxy silane (KH560), and then CA was attached. The immobilization process was optimized, and the catalytic properties of PVDF-attached CA were characterized. The maximum activity recovery of PVDF-KH550-CA was 60%, whereas that of PVDF-KH560-CA was 33%. The Km values of PVDF-KH550-CA, PVDF-KH560-CA, and free enzyme were 9.97 ± 0.37, 12.5 ± 0.2, and 6.18 ± 0.23 mM, respectively, and their Kcat /Km values were 206 ± 2, 117 ± 5, and 488 ± 4 M-1 ·Sec-1 . PVDF-attached CA shows excellent storage stability and reusability, and their half-life values were 82 and 78 days at 4 °C. At 25 °C, they were 50 and 37 days, respectively. PVDF-KH550-CA and PVDF-KH560-CA retained approximately 85% and 72% of the initial activity after undergoing 10 cycles. In the presence of them, the generation rates of CaCO3 were 76% and 65% of the free CA system, which were 1.6 and 1.3 times that of the blank system, respectively. Its role in accelerating CO2 sequestration holds great promise for its practical application.

Population pharmacokinetics of mycophenolic acid and its glucuronide metabolite in lung transplant recipients with and without cystic fibrosis.

1. Cystic fibrosis (CF) is a disease affecting multiple organs that may reduce the systemic exposure of some drugs. The objective of this work was to characterize and compare the population pharmacokinetics (PK) of the immunosuppressant mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) in adult lung transplant recipients with and without CF (NCF) following repeated oral administration of the prodrug mycophenolate mofetil (MMF). 2. A population PK model was developed, with simultaneous modeling of MPA and MPAG, using nonlinear mixed effects modeling. MPA and MPAG serum concentration-time data were adequately described by a compartmental model including enterohepatic recirculation (EHR). Both MPA and MPAG apparent clearance values were significantly elevated (>65%) in patients with CF (24.1 and 1.95 L/h, respectively) compared to the values in the NCF patients (14.5 and 1.12 L/h, respectively), suggesting a notable influence of CF on MPA absorption and disposition. 3. The population PK model developed from our study successfully characterized the absorption, distribution, elimination and EHR of MPA and the metabolite MPAG in lung transplant recipients with or without CF. This model may help to further understand the impact of CF to the overall clinical effects of MPA therapy including immunosuppression and gastrointestinal side effects.

Two-Step Centrifugation Method for Subpicomolar Surface-Enhanced Raman Scattering Detection.

The potentiality of surface-enhanced Raman scattering (SERS) to detect ultralow concentrations of analyte has attracted much attention in detection of trace components in both medicinal and environmental samples. However, detection at trace concentration usually requires sophisticated systems. Here, we present an ultrasensitive and facile SERS approach, a two-step centrifugation method, which achieved a detection limit of 500 fM with phenformin hydrochloride and risperidone as acidic and alkaline analyte, respectively. This method consists of two steps: (1) centrifuging colloidal silver to increase nanoparticles' concentration and to remove small-size nanoparticles, thus increasing the chance of analyte adsorption on large nanoparticles that have strong SERS activity; (2) centrifuging samples after the analytes were mixed with nanoparticles. After the first centrifugation and mixing with aqueous analyte, the colloidal silver is either flocculated (for high-concentration samples) or forms a nanoparticle-analyte complex (for low-concentration samples). Until the second centrifugation, the concentration of analyte and hot-spot formation is significantly increased, and thus a high SERS enhancement factor is obtained. In short, the two-step centrifugation method overcomes drawbacks of the traditional method, which demands not only sophisticated operation but also expensive instruments, to fully exploit the potential of SERS detection.

Photonic bandgap extension of surface-disordered 3D photonic crystals based on the TiO2 inverse opal architecture.

A photonic bandgap (PBG) extension of surface-disordered 3D photonic crystals (PCs) based on the TiO2 inverse opal (TiO2-IO) architecture has been demonstrated. By using a liquid phase deposition (LPD) process based on the controlled hydrolysis of ammonium hexafluorotitanate and boric acid, an extra layer of TiO2 nanoparticles were deposited onto the internal surface of the air voids in the TiO2-IOs to increase their surface roughness, thereby introducing surface disorder in the 3D order structures. The PBG relative width of surface-disordered TiO2-IOs has been broadened significantly, and, compared to the original TiO2-IO, its largest rate of increase (27%) has been obtained. It was found that the PBG relative width increased rapidly at first and then to a much slower rate of change with increase of the duration of the LPD time. A possible cause for this finding is discussed in this Letter.

Preservation of VGLUT1 synapses on ventral calbindin-immunoreactive interneurons and normal locomotor function in a mouse model of spinal muscular atrophy.

Dysfunction in sensorimotor synapses is one of the earliest pathological changes observed in a mouse model [spinal muscular atrophy (SMA)Δ7] of spinal muscular atrophy. Here, we examined the density of proprioceptive and cholinergic synapses on calbindin-immunoreactive interneurons ventral to the lateral motor column. This population includes inhibitory Renshaw interneurons that are known to receive synaptic input from muscle spindle afferents and from motoneurons. At postnatal day (P)13, near the end stage of the disease, the somatic area of calbindin(+) neurons in the L1/L2 and L5/L6 segments was reduced in SMAΔ7 mice compared with controls. In addition, the number and density of terminals expressing the glutamate vesicular transporter (VGLUT1) and the vesicular acetylcholine transporter (VAChT) were increased on calbindin(+) cells in the L1-L2 but not in the L5-L6 segments of SMAΔ7 mice. In addition, the isolated spinal cord of SMA mice was able to generate locomotor-like activity at P4-P6 in the presence of a drug cocktail or in response to dorsal root stimulation. These results argue against a generalized loss of proprioceptive input to spinal circuits in SMA and suggest that the loss of proprioceptive synapses on motoneurons may be secondary to motoneuron pathology. The increased number of VGLUT1(+) and VAChT(+) synapses on calbindin(+) neurons in the L1/L2 segments may be the result of homeostatic mechanisms. Finally, we have shown that abnormal locomotor network function is unlikely to account for the motor deficits observed in SMA mice at P4-6.

The association of matrix metalloproteinase-1 genetic polymorphism (-1607 1G>2G) with colorectal cancer: a meta-analysis.

Several case-control studies on the relation between matrix metalloproteinase (MMP)-1 gene -1607 1G>2G polymorphism and colorectal cancer do not have similar conclusions. The previous two meta-analyses focusing on the same issue also were inconsistent. To further evaluate the relation between the MMP-l gene polymorphism and colorectal cancer, we selected eight case-control studies related to MMP-1 gene polymorphism and colorectal cancer by searching MEDLINE, Embase, CANCERLIT, American Association for Cancer Research, Chinese Biomedical Literature Database, Chinese CNKI, and Wanfang database. Q test and I (2) test were used to test the heterogeneity. We utilized the random effects model to calculate the odds ratio (OR), 95% confidence interval (CI), and the overall effect of P value using the RevMan 5.2 software. The present study included 1,403 patients with colorectal cancer and 1,754 healthy control subjects. Both -1607 2G/2G genotype carriers [OR = 1.59, 95 % CI (1.27-2.01); P < 0.001] and the -1607 2G allele carriers [OR = 1.26, 95% CI (1.05-1.51); P = 0.01] were found to have an increased risk of colorectal cancer. Therefore, we concluded that MMP-1 -1607 1G>2G polymorphism was associated with colorectal cancer.

Properties of Dual-Crosslinked Collagen-Based Membranes as Corneal Repair Material.

Corneal disease has become the second leading cause of blindness in the world. Corneal transplantation is currently considered to be one of the common treatments for vision loss. This paper presents a novel approach utilizing dual-crosslinked membranes composed of polyrotaxane multiple aldehydes (PRAs), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS) in the development process. Collagen was crosslinked, respectively, by EDC/NHS and PRAs to form stable amide bonds and imine groups. Through the formation of a double interpenetrating network, dual-crosslinked (Col-EDC-PRA) membranes exhibited enhanced resistance to collagenase degradation and superior mechanical properties compared to membranes crosslinked with a single crosslinker. Furthermore, Col-EDC-PRA membranes display favorable light transmittance and water content characteristics. Cell experiments showed that Col-EDC-PRA membranes were noncytotoxic and were not significantly different from other membranes. In a rabbit keratoplasty model, corneal stromal repair occurred at 5 months, evidenced by the presence of stromal cells and neo-stroma, as depicted in hematoxylin-eosin-stained histologic sections and optical coherence tomography images of the anterior segment. Moreover, there was no inflammation and corneal neovascularization, as well as no corneal rejection reaction in the surgical area. Overall, the results demonstrated that the dual-crosslinked membranes served effectively for corneal tissue regeneration after corneal defect.

The randomized, single- and multiple- ascending dose studies of the safety, tolerability, pharmacokinetics of CSPCHA115 in healthy Chinese subjects.

CSPCHA115 is a highly selective and potent antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability of single and multiple ascending doses of CSPCHA115 in Chinese healthy subjects. Two phase I studies both adopted a randomized, double-blind, placebo-controlled, single-center, and ascending-dose design. In the single ascending dose (SAD) study, subjects were randomly allocated to receive a single dose of CSPCHA115 (25-1000 mg) or a placebo. In the multiple ascending dose (MAD) study, 100, 200, 400, or 600 mg of CSPCHA115 or placebo were given to subjects once daily for 7 days. PK parameters were estimated by noncompartmental analysis. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs), clinical laboratory tests, electrocardiograms, vital signs, and physical examinations throughout the study period. Forty-eight healthy subjects were enrolled in the SAD study, and 40 healthy subjects were in the MAD study. Following single and multiple administrations, CSPCHA115 was rapidly absorbed with a median time to maximum concentration of ~0.5-3.5 h; and the systemic exposure of CSPCHA115 generally increased dose-proportionally within the dose range studied. Steady-state was approximately achieved by day 5, and <1.5-fold accumulation was observed following multiple doses. Mean terminal half-life was ~8.16-16.43 h after a single dose. CSPCHA115 was well-tolerated in both studies, with a low overall incidence of TEAEs. The most common TEAE related to CSPCHA115 was hypertriglyceridemia. No significant safety concerns were identified in healthy subjects.