Preparation and characterization of pectin-alginate-based microbeads reinforced by nano montmorillonite filler for probiotics encapsulation: Improving viability and colonic colonization.

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.

HPLC-MS/MS analysis of primary alkaloids in rat plasma after oral administration of "Nux vomica - Glycyrrhiza glabra decoction": A pharmacokinetic study.

ETHNOPHARMACOLOGICAL RELEVANCE: Decoction is the most common form of administering traditional Chinese medicine (TCM). During the preparation of decoction, the high temperature and complex chemical environment result in the formation of complex and multiple phases. The differences in drug components in different phases induce gastrointestinal absorption and physiological response. Nux vomica (Strychnos nux-vomica L) is a typical toxic TCM used in China, with remarkable pharmacological activity. In order to reduce its toxicity, nux vomica (NV) is often decocted with Glycyrrhiza glabra (GG) in clinic, and the detoxification mechanism has always been the focus of research interest. Most studies investigated the compatibility of NV-GG, but the in vivo behavior of individual constituents based on phase state has yet to be elucidated. AIM OF THE STUDY: To investigate the pharmacokinetic behavior of typical toxic components in different phase states of "NV-GG decoction" in rat plasma. MATERIALS AND METHODS: The sediment, suspension, colloid and true solution of "NV-GG decoction" was obtained via physical methods. The main components in different phase states were analyzed via reliable UFLC-Q-TOF-MS high-resolution mass spectrometry. A rapid and accurate HPLC-qqq-MS/MS method was established and validated for accurate determination of brucine and strychnine levels in plasma, followed by pharmacokinetic evaluation of different phase states of "NV-GG decoction" in rats. Kinetex F5 100A (50 mm × 3.0 mm, 2.6 µm) column was used for chromatographic separation. Aqueous solution containing acetonitrile and 0.1% formic acid was used as the mobile phase, followed by gradient elution at 0.4 mL/min. Mass spectra were detected by electrospray ionization (ESI) multiple reaction monitoring (MRM) in positive ion mode. RESULTS: Fifteen different alkaloids were detected in different phase states of "NV-GG decoction". Strychnine and brucine, which are toxic components with high content, were selected for quantitative analysis. The established UPLC-qqq-MS/MS method is accurate and reliable with a good linearity (R2 > 0.99) in the respective concentration range, satisfying the quantitative requirements. The pharmacokinetic parameters of different phase states of rats differed significantly after gavage. The deposition phase was the most prominent. The index components showed higher Cmax, AUC0 and Tmax, while the T1/2, MRT, V/F and CL/F were the smallest, with a relatively slow plasma clearance rate in rats. The true solution group showed the lowest Tmax and the fastest absorption. CONCLUSION: This method has been successfully utilized to study the pharmacokinetics of different phase states of "NV-GG decoction". Among the four phases, the deposition phase contributed to a large proportion of the in vivo kinetic behavior similar to that of sustained-release preparations, with slow absorption of toxic components and prolonged peak time. The pharmacokinetic parameters and plasma concentration-time curves of each phase can be used to study toxicity reduction of NV-GG and increase its biocompatibility.

Preferences of Patients with Non-Communicable Diseases for Primary Healthcare Facilities: A Discrete Choice Experiment in Wuhan, China.

OBJECTIVES: To elicit stated preferences of patients with non-communicable diseases (NCDs) for primary healthcare (PHC) facilities and to explore the willingness-to-pay (WTP) for facility attributes. METHODS: A discrete choice experiment (DCE) was conducted through face to face interviews. The DCE survey was constructed by five attributes: type of service, treatment measures, cost, travel time, and care provider. Patients' preferences and willingness to pay for facility attributes were analyzed using a mixed logit model, and interaction terms were used to assess preference heterogeneity among patients with different sociodemographic characteristics. RESULTS: Patients placed different weights on attributes, depending on whether they perceived their health condition as minor or severe. For conditions perceived as minor, patients valued treatment measures (56.60%), travel time (32.34%) and care provider (8.51%) most. For conditions perceived as severe, they valued treatment measures (52.19%), care provider (38.69%), and type of service (7.30%) most. The WTP related to the change from Traditional Chinese Medicine (TCM) service to Modern Medicine (MM) service was the largest for both severity scenarios. For conditions perceived as minor, patients would be willing to pay 102.84 CNY (15.43 USD) for a reduction in travel time to below 30 min. For conditions perceived as severe, WTP related to the change from general service to specialized service and from junior medical practitioner to senior medical practitioner, were highly valued by respondents, worth 107.3 CNY (16.10 USD) and 565.8 CNY (84.87 USD), respectively. CONCLUSIONS: Factors related to the provision of PHC, such as treatment measures, care provider and type of service were highly valued. The findings could contribute to the design of better PHC delivery, improve the participation of patients in PHC, and provide some evidence to promote shared decision-making.

Characterization of selenium-containing polysaccharides isolated from selenium-enriched tea and its bioactivities.

Two novel selenium polysaccharide fractions (SeTPS-1 and SeTPS-2) were isolated purified, characterized from Se-enriched tea. The results showed that the molecular weights and Se content of SeTPS-1 and SeTPS-2 were 1.7 × 104 Da, 1.3 × 104 Da, and 23.50 µg/g and 13.47 µg/g, respectively. SeTPS-1 and SeTPS-2 had absorption spectra typical of selenium esters. SeTPS-1 was composed of glucose and galactose at a molar ratio of 80.1:2.3, respectively, while SeTPS-2 was composed of arabinose, glucose, galactose and galacturonic acid with a molar ratio of 2.04: 48.83: 3.21: 1.30, respectively. Both SeTPS-1 and SeTPS-2 adopted a random coil conformation. Importantly, in vitro assessment of the antioxidant capacity revealed that SeTPS-1 is a more potent antioxidant compared to SeTPS-2. Both compounds were effective at reducing DNA damage induced by H2O2. The promising data suggesting that these compounds confer natural protection against DNA-damaging agents, thereby contributing to the functional food qualities of tea.

[Analysis on the origin and development of elements of reinforcing and reducing needling techniques].

Reinforcing and reducing needling manipulations are important factors affecting clinical therapeutic effect. In the present paper, the relevant elements of the reinforcing and reducing techniques of acupuncture needle including the left- and right-ward twirling, gender, needling at the left and right, front and back parts of the body, needling along or against the running course of the meridian, and their origin and development recorded in ancient Chinese medical books were collected and sorted out, followed by analysis on the understandings of Chinese ancient medical practitioners about them. Results show that the right- or left-ward twirling of needles, gender, and needling at the right or left part, the front or the back part of the body of patients are not the core components of the reinforcing and reducing techniques. Of the three stimulus parameters of needling, named amplitude, frequency and duration which are frequently researched at present, only the duration of single twirling (frequency) was highly noted in GAO Wu's book Zhenjiu Juying (A Collection of Gems in Acupuncture and Moxibustion). It is worthy of being studied in the further. Regarding the stimulation intensity of acupuncture involving the identification of reinforcing or reducing manipulations, the factors influencing the patients' feelings of needling intensity of acupuncture should be studied at the same time.

[The origin, development and mechanisms of special acupuncture needle tools for cutaneous region].

In this paper, we expound the origin and development of special acupuncture needle tools for cutaneous region, and discuss its mechanisms from modern medical theory. By consulting related acupuncture books and literature and in combination with needles used in clinical practice, we conclude that acupuncture needle tools can be divided into skin massage needle (digital pressing, spoon needle, etc.), cutaneous pricking blood needle (shear needle, three-edged needle, plum blossom needle, etc.), subcutaneous shallow puncture needle (intradermal needle, superficial needle, subcutaneous in-dwelling needle), etc. The skin-brain axis is the core of skin stimulation therapy. Mechanical pressure exerted on the skin surface induced by acupuncture stimulation or pressing, microcirculation changes and drug superposition are probably the underlying mechanisms of special skin acupuncture needle tools for treatment of various clinical disorders.

[Summary and core technique on the origin and evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle].

By analyzing the evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle recorded in ancient literature of traditional Chinese medicine, it is found that the main contents of reinforcing-reducing manipulation by lifting and thrusting the needle include manipulating speed change, manual amplitude, insertion layer, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity. Among them, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity are the unnecessary parameters, while the manipulating speed change, manual amplitude and insertion layer are the indispensable parameters. The manipulating speed change is the core of the necessary parameters for the reinforcing-reducing manipulation achieved by lifting and thrusting the needle. Combined with the manual amplitude, the manipulating speed of needle determines the volume of needling stimulation. The insertion layer is decided on the base of the clinical demand. In the core technique of reinforcing-reducing manipulation by lifting and thrusting the needle, the reinforcing is achieved by thrusting the needle forcefully and quickly and then lifting the needle body slowly and evenly back to the original layer. The reducing is achieved by lifting the needle forcefully and quickly and then thrusting the needle body slowly and evenly back to the original layer. The manipulating speed and manual amplitude of needling are the parameters to quantize acupuncture manipulation. In association with the acupuncture effects in human body, these parameters contribute to the interpretation of the dose-effect relationship of acupuncture and the improvement of clinical effects.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry.

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

[Metabolomics of bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS].

The metabonomic techniques were used to study the changes in endogenous metabolites between urines of rats in normal physiological conditions and bovine serum albumin induced allergic reactions, identify potential biomarkers associated with allergic reactions, and then analyze the metabolic pathways and the metabolic mechanisms of allergic reactions. The bovine serum albumin-induced allergic reactions in rats were adopted as a model to detect histamine and tryptase in rat serum and observe the issue morphology of lungs and trachea in rats. UPLC-Q-TOF-MS was applied in metabonomic analysis on urines between control group and allergic reaction model group. Principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were applied to observe the differences in metabolic profiling between urines of the two groups and select differential metabolites. There were significant differences in metabolism spectrum between the model group and the control group. Totally 14 differential metabolites and 4 major metabolic pathways were screened out. The metabonomic research method for urines of rats with bovine serum albumin-induced allergic reactions based on UPLC-Q-TOF-MS was established in this study. It was speculated that the mechanism of bovine serum albumin-induced allergic reactions may involve biosynthesis of isoflavone and folic acid and metabolism of tryptophan, nicotinic acid and nicotinamide. It lays a foundation for further exploration of the application of metabolomics in drug allergy reaction studies.