Comparative pharmacokinetics of 11 major bioactive components between two dosage forms of Qixue Shuangbu Prescription in rats by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.

Comparative pharmacokinetics of four bioactive components in normal and chronic heart failure rats after oral administration of Qiangxin Lishui Prescription by microdialysis combined with ultra-high-performance liquid chromatography.

Qiangxin Lishui Prescription (QLP) has been clinically applied for treating heart failure with remarkable curative effects. A multi-component pharmacokinetic research is very necessary for determining active substances in it. This study aims to profile the traits and differences in the pharmacokinetics of salvianolic acid B, astragaloside IV, calycosin-7-O-ß-D-glucoside and kaempferol in QLP between normal and chronic heart failure (CHF) rats by microdialysis combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sensitive, selective, and online microdialysis combined with the UHPLC-MS/MS method was successfully established and applied to study the pharmacokinetics of QLP. The pathological condition of CHF could lead to the enhancement of systematic exposure and reduction of the metabolic rate of four bioactive components for better bioavailability and therapeutic efficacy. The pharmacokinetic results will provide data support for the clinical application of QLP.

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.

A study of the "Swiss-roll" folding method for placement of self-gripping mesh in TAPP.

BACKGROUND: Using self-gripping mesh eliminates the need for additional mechanical fixation in laparoscopic groin hernia repair when surgeons plan to fix it. However, the mesh's 'self-gripping' characteristic makes it much more difficult to unfold and place. Here, the novel "Swiss-roll" placement method of folding self-gripping mesh is introduced and compared to the common folding placement method. MATERIAL AND METHODS: The cohort of this prospective randomized controlled study included 100 patients who underwent transabdominal preperitoneal (TAPP) groin hernia repair in the Department of Hernia and Abdominal Wall Surgery of Shanghai East Hospital between January and December 2018. The patients were randomly assigned to the "Swiss-roll" folding group or the common folding group. The time required for mesh placement, total surgical duration, and the incidences of postoperative pain and complications were compared. RESULTS: The times required for mesh placement in the "Swiss-roll" and common folding groups were 155.10 ± 48.66 and 202.80 ± 61.05 sec, respectively. The "Swiss-roll" folding method significantly shortened the time required for mesh placement (p = 0.000). There were no significant differences in total surgical duration and the incidences of postoperative pain and complications between the two groups. CONCLUSIONS: The "Swiss-roll" folding method facilitates self-gripping mesh placement without increasing the incidence of complications and recurrences in TAPP.

MiR-122 is involved in immune response by regulating Interleukin-15 in the orange-spotted grouper (Epinephelus coioides).

Epinephelus coioides is an important economic culture marine fish and is susceptible to various pathogenic diseases. Increasingly evidences showed that miRNAs participated in the regulation of the cell proliferation, differentiation and immune response. MiR-122 has been reported to play an essential role in immune response by triggering an inflammatory reaction. However, the function of miR-122 in response to bacterial infection is unclear in Epinephelus coioides. Herein, we report that miR-122 is involved in response to Aeromonas hydrophila infection of grouper spleen cells (GS). IL-15, IL-6 and IL-1ß are inhibited in overexpression miR-122 GS cells, while induced in silence miR-122 GS cells. In addition, IL-15 is predicted to be the target gene of miR-122, which is further confirmed by LUC. Taken together, we propose that miR-122 regulates the immune response to bacterial infection by triggering IL-15.

A preliminary multicenter evaluation of endoscopic sublay repair for ventral hernia from China.

BACKGROUND: For ventral hernia, endoscopic sublay repair (ESR) may overcome the disadvantages of open sublay and laparoscopic intraperitoneal onlay mesh repair. This retrospective study presents the preliminary multicenter results of ESR from China. The feasibility, safety, and effectiveness of ESR were evaluated; its surgical points and indications were summarized. METHODS: The study reviewed 156 ventral hernia patients planned to perform with ESR in ten hospitals between March 2016 and July 2019. Patient demographics, hernia characteristics, operative variables, and surgical results were recorded and analyzed. RESULTS: ESR was performed successfully in 153 patients, 135 with totally extraperitoneal sublay (TES) and 18 with transabdominal sublay (TAS). In 19 patients, TES was performed with the total visceral sac separation (TVS) technique, in which the space separation is carried out along the peritoneum, avoiding damage to the aponeurotic structure. Endoscopic transversus abdominis release (eTAR) was required in 17.0% of patients, and only 18.3% of patients required permanent mesh fixation. The median operative time was 135 min. Most patients had mild pain and resume eating soon after operation. No severe intraoperative complications occurred. Bleeding in the extraperitoneal space occurred in two patients and was stopped by nonsurgical treatment. Seroma and chronic pain were observed in 5.23 and 3.07% of patients. One recurrence occurred after TAS repair for an umbilical hernia. CONCLUSION: ESR is feasible, safe, and effective for treating ventral hernias when surgeons get the relevant surgical skills, such as the technique of "partition breaking," TVS, and eTAR. Small-to-medium ventral hernias are the major indications.

Comparative pharmacokinetics of seven bioactive components after oral administration of crude and processed Qixue Shuangbu Prescription in chronic heart failure rats by microdialysis combined with UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Qixue Shuangbu Prescription (QSP) is a classical traditional Chinese medicine prescription, which has widely used for the treatment of chronic heart failure (CHF). Preliminary clinical studies have shown that the efficacy of processed QSP (P-QSP) in treating CHF is greater than crude QSP (C-QSP). However, the pharmacokinetic characteristics of its major bioactive components under pathological conditions are unclear. AIM OF STUDY: This study aims to compare pharmacokinetics of seven bioactive components after oral administration of C-QSP and P-QSP in CHF model rats. MATERIALS AND METHODS: Ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ferulic acid, astragaloside IV, calycosin-7-O-ß-D-glucoside, and paeoniflorin in QSP were used as the target components. CHF model in rats was induced by the intraperitoneal injection of doxorubicin. A microdialysis combined with UPLC-MS/MS method was first established to compare the pharmacokinetics of seven major bioactive components in CHF model rats after oral administration of C-QSP and P-QSP. RESULTS: This method was successfully applied to the pharmacokinetic investigation of seven major components of C-QSP and P-QSP following oral administration in CHF model rats. Compared with the C-QSP group, the Cmax, AUC0-t and AUC0-∞ of ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ferulic acid, astragaloside IV and paeoniflorin significantly increased (P < 0.05) in the P-QSP group, which suggested that the absorptivity and bioavailability were increased. Lower T1/2, MRT0-t of ginsenoside Rb1, gerulic acid and higher T1/2, MRT0-t of ginsenoside Rb1, astragaloside IV, paeoniflorin in the P-QSP group, which indicated that eliminated more quickly or slowly, respectively. CONCLUSIONS: The pharmacokinetic parameters of bioactive components were significantly changed for better bioavailability and absorption, longer lasting time elimination, which were beneficial for enhancing therapeutic efficacy in the P-QSP group. This study will provide a new perspective to explain the pharmacokinetic-pharmacodynamic correlation of P-QSP on the treatment of CHF.

Functionalized Strategies and Mechanisms of the Emerging Mesh for Abdominal Wall Repair and Regeneration.

Meshes have been the overwhelmingly popular choice for the repair of abdominal wall defects to retrieve the bodily integrity of musculofascial layer. Broadly, they are classified into synthetic, biological and composite mesh based on their mechanical and biocompatible features. With the development of anatomical repair techniques and the increasing requirements of constructive remodeling, however, none of these options satisfactorily manages the conditional repair. In both preclinical and clinical studies, materials/agents equipped with distinct functions have been characterized and applied to improve mesh-aided repair, with the importance of mesh functionalization being highlighted. However, limited information exists on systemic comparisons of the underlying mechanisms with respect to functionalized strategies, which are fundamental throughout repair and regeneration. Herein, we address this topic and summarize the current literature by subdividing common functions of the mesh into biomechanics-matched, macrophage-mediated, integration-enhanced, anti-infective and antiadhesive characteristics for a comprehensive overview. In particular, we elaborate their effects separately with respect to host response and integration and discuss their respective advances, challenges and future directions toward a clinical alternative. From the vastly different approaches, we provide insight into the mechanisms involved and offer suggestions for personalized modifications of these emerging meshes.

Employing a Xiphoid-umbilicus Approach in an Endoscopic Totally Extraperitoneal Procedure for the Preperitoneal Repair of Midline Ventral Hernias.

OBJECTIVES: Endoscopic totally extraperitoneal sublay (TES) repair seems to be a promising procedure for treating ventral hernias because repairing at the preperitoneal layer reduces damage to the natural musculoaponeurotic structures of the abdominal wall. This article reports the preliminary surgical results after such a procedure with a xiphoid-umbilicus approach for a midline ventral hernia of the middle-upper abdomen. MATERIALS AND METHODS: Fifteen cases with a small midline ventral hernia scheduled for preperitoneal repair with a TES procedure with a xiphoid-umbilicus approach were included. Patient demographics, hernia characteristics, operative variables, and surgical results were recorded and analyzed. RESULTS: The patients' average age was 55.80±15.33 years, body mass index was 26.49±2.98, defect size was 4.59±2.28 cm2, and the most frequent region was M3. Five of 15 procedures were conducted in a bottom-up direction, and 10 of 15 with single-port surgery. Only 1 repair failed due to severe peritoneal damage. The operation duration was 120.4±47.7 minutes. All patients recovered quickly and uneventfully, and no case needed readmission. No severe intraoperative and postoperative complications occurred. Only 1 case developed seroma, and there was no surgical site infection, pain, trocar site hernia, and recurrence observed during short-term follow-up (3 to 12 mo). CONCLUSIONS: Endoscopic preperitoneal repair helps reduce damage to the abdominal wall during a TES procedure. Compared with a suprapubic approach, employing a xiphoid-umbilicus approach facilitates preperitoneal repair for small ventral hernias of the middle-upper abdomen. This will be a future option for minimally invasive surgical repair of such ventral hernias (Supplemental Digital Content 1, Video, http://links.lww.com/SLE/A287).

Novel XTENylated AWRK6 analog with hypoglycemic activity, and anti-HSV-2 potential in combination with double shRNA.

AIMS: To design and evaluate a novel AWRK6 peptide-based long-acting GLP-1 receptor agonist (GLP-1RA) conjugated a recombinant polyethylene glycol mimetic (XTEN protein) with significant therapeutic potential on type 2 diabetes mellitus (T2DM) alone as well as Herpes simplex virus type 2 (HSV-2) infection in combination with double shRNA. MAIN METHODS: First, four AWRK6 analogs (termed XA-1 to XA-4) were designed and produced by solid phase synthesis strategy. Further surface plasmon resonance (SPR) measurement and in vitro cAMP accumulation assay were performed to detect the GLP-1R binding affinities and GLP-1R activation, respectively. The in vivo efficacy evaluation including pharmacokinetic test, oral glucose tolerance test (OGTT), hypoglycemic duration test and chronic pharmacodynamics study in rodent animals were all carefully performed. KEY FINDINGS: Four XA peptides were synthesized with purity >99%. High binding affinity as well as activation potency of XA-4 for GLP-1R were demonstrated by SPR and cell-based luciferase reporter assay, respectively. Additionally, XA-4 exhibited the long-lasting antidiabetic effects in the multiple OGTTs, hypoglycemic duration test and chronic study in mice. Furthermore, combined treatment of XA-4 and double shRNA (D-shRNA) achieved potent antiviral effects in HSV-2 infected HEK293 cells. SIGNIFICANCE: XA-4 exhibited promising pharmaceutical potential to be a therapeutic drug for treating T2D, and also held potential to against the HSV-2 infection, which is really an accidental discovery. The strategy of recombinant XTENylation can also be applied to other peptides or small molecules for the development of long-acting therapeutic drugs.

Elucidation of the Mechanisms and Molecular Targets of Sanhuang Xiexin Decoction for Type 2 Diabetes Mellitus Based on Network Pharmacology.

Sanhuang Xiexin Decoction (SXD) is commonly used to treat type 2 diabetes mellitus (T2DM) in clinical practice of traditional Chinese medicine (TCM). In order to elucidate the specific analysis mechanisms of SXD for T2DM, the method of network pharmacology was applied to this article. First, the effective ingredients of SXD were obtained and their targets were identified based on the TCMSP database. The T2DM-related targets screened from the GEO database were also collected by comparing the differential expressed genes between T2DM patients and healthy individuals. Then, the common targets in SXD-treated T2DM were obtained by intersecting the putative targets of SXD and the differential expressed genes of T2DM. And the protein-protein interaction (PPI) network was established using the above common targets to screen key genes through protein interactions. Meanwhile, these common targets were used for GO and KEGG analyses to further elucidate how they exert antidiabetic effects. Finally, a gene pathway network was established to capture the core one in common targets enriched in the major pathways to further illustrate the role of specific genes. Based on the data obtained, a total of 67 active compounds and 906 targets of SXD were identified. Four thousand one hundred and seventy-six differentially expressed genes with a P value < 0.005 and ∣log2(fold change) | >0.5 were determined between T2DM patients and control groups. After further screening, thirty-seven common targets related to T2DM in SXD were finally identified. Through protein interactions, the top 5 genes (YWHAZ, HNRNPA1, HSPA8, HSP90AA1, and HSPA5) were identified. It was found that the functional annotations of target genes were associated with oxygen levels, protein kinase regulator, mitochondria, and so on. The top 20 pathways including the PI3K-Akt signaling pathway, cancers, HIF-1 signaling pathway, and JAK-STAT signaling pathway were significantly enriched. CDKN1A was shown to be the core gene in the gene-pathway network, and other several genes such as CCND1, ERBB2, RAF1, EGF, and VEGFA were the key genes for SXD against T2DM. Based on the network pharmacology approach, we identified key genes and pathways related to the prognosis and pathogenesis of T2DM and also provided a feasible method for further studying the chemical basis and pharmacology of SXD.

Policies of US Companies Offering Direct-to-Consumer Laboratory Tests.

This qualitative study assesses the practices and policies of companies offering direct-to-consumer laboratory testing in the US.