Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine.

Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.

Construction of highly stable, monodisperse water-in-water Pickering emulsions with full particle coverage using a composite system of microfluidics and helical coiled tube.

Water-in-water (W/W) Pickering emulsions, exhibit considerable potential in the food and pharmaceutical fields owing to their compartmentalization and high biocompatibility. However, constrained by the non-uniform distribution of shear forces during emulsification or the spatial obstruction in polydimethylsiloxane (PDMS) passive microfluidic platform, the existing methods cannot generate monodisperse W/W Pickering emulsions with high particle coverage rate, thereby limiting their applications. Herein, a novel microfluidic system is designed for the preparation of monodisperse and highly particle-covered W/W Pickering emulsions under mild conditions. pH-responsive Polyethylene glycol (PEG)/phosphate aqueous two-phase system (ATPS) is used for the emulsions' preparation. Notably, a coverage rate of 96 ± 3 % is obtained by adjusting the length of the helical coiled tube, as well as the size and contact angle of genipin cross-linked BSA (BSA-GP) particles. Moreover, these W/W Pickering emulsions, with surfaces almost completely covered, can maintain monodisperse (Ncoal = 1.18 ± 0.03) for one day. Furthermore, the results of ranitidine hydrochloride (RH) release demonstrated that the drug release rate of W/W Pickering emulsions in the simulated gastric fluid (SGF) was 10 times faster than that in the neutral solution. We believe that the highly particle-covered monodisperse W/W Pickering emulsions possess great potential applications in bioencapsulation for foods and drug delivery.

Construction of Dome-Shaped 3D Corneal Epithelial Tissue Models Based on Eyeball-Shaped Gel Microspheres.

By overcoming interspecies differences and mimicking the in vivo microenvironment, three-dimensional (3D) in vitro corneal models have become a significant novel tool in contemporary ophthalmic disease research. However, existing 3D corneal models struggle to replicate the actual human corneal environment, especially the dome-shaped physiological structure with adjustable curvature. Addressing these challenges, this study introduces a straightforward method for fabricating collagen/chitosan-alginate eyeball-shaped gel microspheres with a Janus structure via a two-phase aqueous system, used subsequently to construct in vitro 3D corneal epithelial tissue models. By adjusting the diameter ratio of collagen/chitosan to alginate droplets, we can create eyeball-shaped gel microspheres with varying curvatures. Human corneal epithelial cells were seeded on the surfaces of these microspheres, leading to the formation of in vitro 3D corneal epithelial tissues characterized by dome-like multilayers and tight junctions. Additionally, the model demonstrated responsiveness to UVB exposure through the secretion of reactive oxygen species (ROS) and proinflammatory factors. Therefore, we believe that in vitro 3D corneal epithelial tissue models with dome-shaped structures hold significant potential for advancing ophthalmic research.

Preparation of Controlled Multicompartmental Gel Microcarriers Based on Aqueous Two-Phase Emulsions for 3D Partitioned Cell Coculture In Vitro.

A facile method was proposed for preparing controllable multicompartment gel microcarriers using an aqueous two-phase emulsion system. By leveraging the density difference between the upper polyethylene glycol solution and the lower dextran-calcium chloride (CaCl2) solution in the collection solution and the high viscosity of the lower solution, controllable fusion of core-shell droplets made by coextrusion devices was achieved at the water/water (w/w) interface to fabricate microcarriers with separated core compartments. By adjusting the sodium alginate concentration, collected solution composition, and number of fused liquid droplets, the pore size, shape, and number of compartments could be controlled. Caco-2 and HepG2 cells were encapsulated in different compartments to establish gut-liver coculture models, exhibiting higher viability and proliferation compared to monoculture models. Notably, significant differences in cytokine expression and functional proteins were observed between the coculture and monoculture models. This method provides new possibilities for preparing complex and functional three-dimensional coculture materials.

All-aqueous droplets-templated tailorable core-shell alginate microspheres for constructing vascularized intestinal mucosain vitromodels.

Recently,in vitromodels of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevantin vitromodels of intestinal mucosa is the creation of three-dimensional microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core-shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core-shell Alg microspheres provide a valuable method for generatingin vitromodels of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.

Research progress on the treatment of perimenopausal insomnia with Chaihu Jia Longgu Muli decoction based on brain-intestine-bacteria axis: A review.

With the progress and rapid societal development, women are confronted with multifaceted pressures in their lives, encompassing familial and other domains. Furthermore, during the perimenopausal phase, endocrine equilibrium is disrupted, leading to the emergence of psychological and physiological health challenges. Insomnia is a prevalent symptom among perimenopausal individuals. The brain-gut-bacteria axis assumes a pivotal role in the prevention, diagnosis, and management of perimenopausal insomnia. Chaihu Jia Longgu Muli decoction is a commonly prescribed remedy for addressing perimenopopausal insomnia. Consequently, this paper aims to investigate the interplay between the brain-gut-bacteria axis, intestinal microbiota, and the pathogenesis of perimenopausal insomnia. The study focuses on examining the regulatory effects of Chaihu Jia Longgu Muli decoction on the nervous system, intestinal microbiota, and the hypothalamus-pituitary-adrenal axis. Additionally, it explores the mechanisms underlying Hujia Longgu Muli decoction in mitigating perimenopausal insomnia.

Study on the active ingredients and mechanism of Jiaotai Pill in the treatment of primary insomnia based on network pharmacology and GEO statistics: A review.

OBJECTIVE: To explore the active components and mechanism of Jiaotai Pill (JTP) in the treatment of primary insomnia (PI) based on gene expression omnibus. METHODS: The main active components of Jiaotai Pills were obtained by TCMSP and literature mining, and the targets of the active components of Jiaotai Pills were predicted. The targets were verified and standardized by Uniprot database. PI-related targets were obtained from GeneCards, OMIM, DrugBank, PharmGKB, and TTD databases. Obtaining an intersection action target point of the Jiaotai pill and the PI by using a Venny diagram; Gene chip data (GSE208668) was downloaded from gene expression omnibus database, and then gene probe enrichment analysis (GSEA) was used to screen the differentially expressed genes between PI patients and normal controls, and molecular docking was used to virtually verify the screened differentially expressed genes with potential active compounds. RESULTS: 21 active components and 263 potential targets of Jiaotai Pill were screened by database analysis and literature mining, 112 of which were intersected with PI. Molecular docking results showed that quercetin, EGCG, kaempferol, R-kanatin, stigmasterol, berberine and other core active components had good docking activity with related differential genes. CONCLUSION: Jiaotai Pill can regulate the release of inflammatory factors through multiple active ingredients, multiple disease targets, multiple biological pathways and multiple pathways to achieve the purpose of treating PI, which provides a theoretical basis for the clinical treatment of PI and broadens the clinical use of Jiaotai Pill.

Multifeature Fusion Classification Method for Adaptive Endoscopic Ultrasonography Tumor Image.

Endoscopic ultrasonography (EUS) has been found to be of great advantage in the diagnosis of digestive tract submucosal tumors. However, EUS-based diagnosis is limited by variability in subjective interpretation on the part of doctors. Tumor classification of ultrasound images with the computer-aided diagnosis system can significantly improve the diagnostic efficiency and accuracy of doctors. In this study, we proposed a multifeature fusion classification method for adaptive EUS tumor images. First, for different ultrasound tumor images, we selected the region of interest based on prior information to facilitate the estimation in the subsequent works. Second, we proposed a method based on image gray histogram feature extraction with principal component analysis dimensionality reduction, which learns the gray distribution of different tumor images effectively. Third, we fused the reduced grayscale features with the improved local binary pattern features and gray-level co-occurrence matrix features, and then used the multiclassification support vector machine. Finally, in the experiment, we selected the 431 ultrasound images of 109 patients in the hospital and compared the experimental effects of different features and different classifiers. The results revealed that the proposed method performed best, with the highest accuracy of 96.18% and an area under the curve of 99%. It is evident that the method proposed in this study can efficiently contribute to the classification of EUS tumor images.

Microfluidic aqueous two-phase system-based nitrifying bacteria encapsulated colloidosomes for green and sustainable ammonium-nitrogen wastewater treatment.

A novel strategy was proposed for preparing micro-scale monodisperses nitrifying bacteria (NB) encapsulated Ca-Alg@CaCO3 colloidosomes by exploiting capillary microfluidic device, as an attempt to treat ammonium-nitrogen wastewater in an environment-friendly, efficient and repeatable manner based on the aqueous two-phase (ATPS) system. By complying with the spatial confined urease mediate biomineralization reactions, ATPS droplets (Dextran in Polyethylene glycol) containing urease, NB regent and alginate were used as templates to prepare 500 µm Ca-Alg@CaCO3 colloidosomes with 16.48 Mpa mechanical strength. The activity of NB encapsulated in the colloidosomes was high. The simulated wastewater treated with the colloidosomes achieved a high removal rate even at harsh temperature and pH value. In both simulated and real wastewater treatment, prolonged reuse times (216 h) with high removal rate (＞90%, after being applied 72 h) were obtained by using Ca-Alg@CaCO3 colloidosomes, as compared with that (96 h) by using general alginate microbeads.

Aqueous two-phase emulsions-templated tailorable porous alginate beads for 3D cell culture.

A facile method was developed to produce porous alginate beads (PABs) with a controllable interconnected porous structure with aqueous two phase (ATPS) emulsions as template for 3D cell culture. ATPS emulsions, containing two biocompatible immiscible aqueous phases of cell/dextran (Dex) mixture and alginate (Alg)/polyethylene glycol (PEG) mixture and stabilized by mPEG-BSA particles, were introduced to form PABs. The pore size of PABs could be controlled by changing the emulsification frequency and the volume ratio between the ATPS emulsions and PEG-Alg solution. Moreover, cells could be directly encapsulated in the interconnected pores due to the excellent biocompatibility of ATPS. HeLa and human liver cancer cells encapsulated in the PABs present stronger cell activity (>95 %), proliferation, and enhanced functions compared with the cells encapsulated in general alginate beads (GABs). It is believed that the PABs is a promising microcarriers for 3D cell culture in vitro.

Aqueous Two-Phase Droplet-Templated Colloidosomes Composed of Self-Formed Particles via Spatial Confined Biomineralization.

A facile and green approach is developed for fabricating colloidosomes with well-controlled size and structure from the microfluidic-generated aqueous two-phase system (ATPS) emulsion droplet. Unlike other methods that rely on self-assembly of externally added colloidal particles at the emulsion interface, urease-mediated biomineralization induced by "drainage" is introduced to form CaCO3 particles at the alginate emulsion interface for preparing Ca-alg@CaCO3 colloidosomes. Two types of bioactive molecules (bovine serum albumin and catalase) can be encapsulated with high efficiency (>85%) because of the partitioning effect of the ATPS and high viscosity of alginate solution. The encapsulated bioactive molecules can be controllably released by regulating the compactness of colloidosomes. Moreover, after being freeze-dried or dried at 37 °C, the activity of catalase in colloidosomes is obviously higher than that in alginate hydrogels, which confirms that the Ca-alg@CaCO3 structure has strong protection for inclusions. We believe that the biocompatible and controllable Ca-alg@CaCO3 colloidosomes possess great potential applications in bioencapsulation for foods, daily chemicals, and synthetic protocell formation.

Monodisperse Alginate Microcapsules with Spatially Confined Bioactive Molecules via Microfluid-Generated W/W/O Emulsions.

A simple process is developed for the one-step preparation of dual-compartment alginate microcapsules with controlled size and structure from microfluid-generated water-in-water-in-oil (W/W/O) emulsion droplet. Unlike other methods that rely on transient W/W/O emulsion droplet, we introduce an aqueous two-phase system (ATPS) to form a stable W/W/O emulsion droplet as a template for preparing dual-compartment alginate microcapsules. Two different bioactive molecules are able to be spatially confined encapsulated in the shell and core of alginate microcapsules due to the partitioning effect of ATPS and the high viscosity of alginate solution. Moreover, an enzyme cascade reaction with a spatial confined glucose oxidase and horseradish peroxidase in the shell and core of alginate microcapsules confirms its excellent biocompatibility and high activity. This method provides a green platform for enzyme-catalyzed tandem reactions and controlled sequential release of multiple drugs based on alginate microcapsules.

Cost-effectiveness comparison of routine transfusion with restrictive and liberal transfusion strategies for surgical patients in China.

BACKGROUND AND OBJECTIVES: A health industry standard recommending restrictive transfusion is to be in effect in China in April 2019. We aim to explore its potential economic and clinical impacts among surgical patients. MATERIALS AND METHODS: A decision tree model was applied to compare cost-effectiveness of current routine transfusion in China, a restrictive (transfusion at Hb < 8 g/dl or ischaemic symptoms) and a liberal (transfusion at Hb < 10 g/dl) strategy. Parameters were estimated from empirical data of 25 227 surgical inpatients aged ≥30 years in a multicenter study and supplemented by meta-analysis when necessary. Results are shown for cardio-cerebral-vascular (CCV) surgery and non-CCV (orthopaedics, general, thoracic) surgery separately. RESULTS: Per 10 000 patients in routine, restrictive, liberal transfusion scenarios, total spending (transfusion and length of stay related) was 7·67, 7·58 and 9·39 million CNY (1 CNY × 0.157 = 1 US dollar) for CCV surgery and 6·35, 6·70 and 8·09 million CNY for non-CCV surgery; infectious and severe complications numbered 354, 290, and 290 (CCV) and 315, 286, and 330 (non-CCV), respectively. Acceptability curves showed high probabilities for restrictive strategy to be cost-effective across a wide range of willingness-to-pay values. Such findings were mostly consistent in sensitivity and subgroup analyses except for patients with cardiac problems. CONCLUSION: We showed strong rationale, succeeding previous findings only in cardiac or joint procedures, to comply with the new standard as restrictive transfusion has high potential to save blood, secure safety, and is cost-effective for a wide spectrum of surgical patients. Experiences should be further summarized to pave the way towards individualized transfusion.

Effect of a risk-stratified intervention strategy on surgical complications: experience from a multicentre prospective study in China.

OBJECTIVES: To develop a risk-stratified intervention strategy and evaluate its effect on reducing surgical complications. DESIGN: A multicentre prospective study with preintervention and postintervention stages: period I (January to June 2015) to develop the intervention strategy and period II (January to June 2016) to evaluate its effectiveness. SETTING: Four academic/teaching hospitals representing major Chinese administrative and economic regions. PARTICIPANTS: All surgical (elective and emergent) inpatients aged ≥14 years with a minimum hospital stay of 24 hours, who underwent a surgical procedure requiring an anesthesiologist. INTERVENTIONS: Targeted complications were grouped into three categories (common, specific, serious) according to their incidence pattern, severity and preventability. The corresponding expert consensus-generated interventions, which focused on both regulating medical practices and managing inherent patient-related risks, were implemented in a patient-tailored way via an electronic checklist system. PRIMARY AND SECONDARY OUTCOMES: Primary outcomes were (1) in-hospital death/confirmed death within 30 days after discharge and (2) complications during hospitalisation. Secondary outcome was length of stay (LOS). RESULTS: We included 51 030 patients in this analysis (eligibility rate 87.7%): 23 413 during period I, 27 617 during period II. Patients' characteristics were comparable during the two periods. After adjustment, the mean number of overall complications per 100 patients decreased from 8.84 to 7.56 (relative change 14.5%; P<0.0001). Specifically, complication rates decreased from 3.96 to 3.65 (7.8%) for common complications (P=0.0677), from 0.50 to 0.36 (28.0%) for specific complications (P=0.0153) and from 3.64 to 2.88 (20.9%) for serious complications (P<0.0001). From period I to period II, there was a decreasing trend for mortality (from 0.64 to 0.53; P=0.1031) and median LOS (by 1 day; P=0.8293), without statistical significance. CONCLUSIONS: Implementing a risk-stratified intervention strategy may be a target-sensitive, convenient means to improve surgical outcomes.

Antiproliferative activity of Farnesol in HeLa cervical cancer cells is mediated via apoptosis induction, loss of mitochondrial membrane potential (ΛΨm) and PI3K/Akt signalling pathway.

PURPOSE: Cervical cancer remains the most gruesome health problem in women worldwide as it ranks third in incidence. Despite recent developments in the treatment options of cervical cancer, the survival of patients not fit for surgical treatment rather remains poor. The main purpose of the current research was to determine the anticancer effect of farnesol in HeLa human cervical cancer cells together with studying its impact on apoptosis induction, mitochondrial membrane potential (MMP) and PI3K/Akt signalling cascade. METHODS: Cell viability was estimated by MTT assay while clonogenic assay was used to assess the effects on colony formation tendency in these cells. Fluorescence microscopy indicated apoptosis induction while flow cytometry showed the farnesol effects on the loss of MMP. RESULTS: Farnesol exerted both dose and time-dependent antiproliferative effects on cervical cancer cells with IC50 values of 33.5, 23.8 and 17.6 µM at 24, 48 and 72 hrs time intervals, respectively. Colony formation of HeLa cells was considerably affected in a dose-dependent manner with the addition of farnesol to the cell culture. Farnesol-treated cells mostly emitted orange fluorescence indicating apoptotic cell death and this effect increased with increasing dose of the compound. Furthermore, farnesol induced considerable reduction in the number of cells with depolarized mitochondria corresponding to a reduction of MMP. With increase in the dosage of farnesol, there was a noticeable decrease in the expression levels of PI3K, p-PI3K and p-Akt proteins. CONCLUSIONS: In brief, this study showed that farnesol -a naturally occurring sesquiterpene- exerts powerful antiproliferative activity via apoptosis induction, loss of MMP and downregulation of the expression levels of PI3K, p-PI3K and p-Akt proteins.

Light and Magnetic Dual-Responsive Pickering Emulsion Micro-Reactors.

Emulsion droplets can serve as ideal compartments for reactions. In fact, in many cases, the chemical reactions are supposed to be triggered at a desired position and time without change of the system environment. Here, we present a type of light and magnetic dual-responsive Pickering emulsion microreactor by coadsorption of light-sensitive titania (TiO2) and super paramagnetic iron oxide (Fe3O4) nanoparticles at the oil-water interface of emulsion droplets. The droplets encapsulating different reactants in advance can be driven close to each other by an external magnetic field, and then the chemical reaction is triggered by UV illumination due to the contact of the isolated reactants as a result of droplet coalescence. An insight into the incorporation of hydrophobic TiO2 and hydrophilic Fe3O4 nanoparticles simultaneously at the emulsion interface is achieved. On the basis of that, an account is given of the coalescence mechanism of the Pickering emulsion microreactors. Our work not only provides a novel Pickering emulsion microreactor platform for triggering chemical reactions in a nonintrusive and well-controlled way but also opens a promising avenue to construct multifunctional Pickering emulsions by assembly of versatile building block nanoparticles at the interface of emulsion droplets.

Polymer-Protein Conjugate Particles with Biocatalytic Activity for Stabilization of Water-in-Water Emulsions.

Water-in-water (w/w) emulsions are attractive microcompartmentalized platforms due to their outstanding biocompatibility. To address the main disadvantage of poor stability that hampers their practical application, here we report a novel type of polymer-protein conjugate emulsifier obtained by Schiff base synthesis to stabilize w/w emulsions. In particular, the proposed mild approach benefits the modification of proteins of suitable size and wettability as particulate emulsifiers retaining their bioactivity. As demonstrated in a model system, the methoxy polyethylene glycol (mPEG)-urease conjugate particles anchor at the w/w interfaces, where they serve as an effective emulsifier-combined-catalyst and catalyze the hydrolysis of urea in water to ammonium carbonate. Our study is unique in that it employs bioactive particles to stabilize w/w emulsions. Considering the characteristics of all-aqueous, compartmental and interfacial biocatalysis of the system, it will open up new possibilities in the life sciences.

Pneumatic microfluidics-based multiplex single-cell array.

Large-scale single-cell arrays are urgently required for current high-throughput screening of cell function and heterogeneity. However, the rapid and convenient generation of large-scale single-cell array in a multiplex and universal manner is not yet well established. In this paper, we report a simple and reliable method for the generation of a single-cell array by combining pneumatic microvalve arrays (PµVAs) and hydrodynamic single-cell trapping sites in a single microfluidic device. The PµVAs, which can be precisely controlled by actuated pressures, were designed to guide multiple types of cells being trapped in the corresponding single-cell trapping sites located in the fluidic channel. According to the theoretical demonstration and computational simulation, we successfully realized a multiplex single-cell array with three different types of cells by a step-by-step protocol. Furthermore, the analysis of cellular esterase heterogeneity of the three types of cells was concurrently implemented in the device as a proof-of-concept experiment. All the results demonstrated that the method developed in the current study could be applied for the generation of large-scale single-cell array with multiple cell types, which would be also promising and helpful for single-cell-based high-throughput drug test, multipurpose immunosensor and clinical diagnosis.

High throughput and multiplex localization of proteins and cells for in situ micropatterning using pneumatic microfluidics.

Micropatterning technologies are emerging as an enabling tool for various microfluidic-based applications in life sciences. However, the high throughput and multiplex localization of multiple bio-components in a microfluidic device has not yet been well established. In this paper, we describe a simple and in situ micropatterning method using an integrated microfluidic device with pneumatic microstructures (PµSs) for highly controllable immobilization of both proteins and cells in a high throughput, geometry-dynamic, and multi-patterning way. The precise Pluronic F127 passivation of a microchamber surface except the PµS-blocked regions was performed and characterized, and the spatial dynamics and consistency of both the PµSs and protein/cell micropatterning were optically evaluated and quantitatively demonstrated too. Furthermore, a systematic investigation of PµS-assisted micropatterning in microfluidics was carried out. The feature of high throughput and spatial control of micropatterning can be simply realized by using the well-designed PµS arrays. Meanwhile, the co-micropatterning of different proteins (bovine serum albumin and chicken egg albumin) and cells (human umbilical vein endothelial cells and human hepatocellular carcinoma cells) in a microfluidic device was successfully accomplished with the orderly serial manipulation of PµS groups. We demonstrate that PµS-assisted micropatterning can be applied as a convenient microfluidic component for large-scale and diversified protein/cell patterning and manipulation, which could be useful for cell-based tissue organization, high-throughput imaging, protein-related interactions and immunoassays.