Application of multiple strategies to enhance oleanolic acid biosynthesis by engineered Saccharomyces cerevisiae.

Oleanolic acid and its derivatives are widely used in the pharmaceutical, agricultural, cosmetic and food industries. Previous studies have shown that oleanolic acid production levels in engineered cell factories are low, which is why oleanolic acid is still widely extracted from traditional medicinal plants. To construct a highly efficient oleanolic acid production strain, rate-limiting steps were regulated by inducible promoters and the expression of key genes in the oleanolic acid synthetic pathway was enhanced. Subsequently, precursor pool expansion, pathway refactoring and diploid construction were considered to harmonize cell growth and oleanolic acid production. The multi-strategy combination promoted oleanolic acid production of up to 4.07 g/L in a 100 L bioreactor, which was the highest level reported.

Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential.

3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.

Efficacy of Chinese Herbal Medicine Formula in the Treatment of Mild to Moderate Erectile Dysfunction: Study Protocol for a Multi-Center, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Introduction: Erectile dysfunction (ED) is a prevalent condition in urology, primarily managed with PDE5 inhibitors (PDE5Is). However, approximately 20% of patients do not experience improvement in overall sexual satisfaction (OS) after taking PDE5Is. Among these, traditional Chinese medicine (TCM) has emerged as a complementary approach, with formulas like Hongjing I granules (HJIG) showing promise in preliminary studies. This study aims to rigorously evaluate the effectiveness and safety of HJIG in mild to moderate ED cases, assessing improvement in both sexual function and TCM pattern alignment. Methods: This study is a randomized, double-blind, placebo-controlled multicentre trial. Recruitment will be conducted from patients who have a strong willingness to try using only traditional Chinese medicine treatment (This is very common in traditional Chinese medicine hospitals.). A total of 100 patients diagnosed with mild to moderate ED caused by qi deficiency and blood stasis will be recruited and randomly assigned to receive one of two treatments: HJIG (N = 50) or placebo (N = 50). Patients will receive 8 weeks of treatment and a 16-week follow-up starting from the fourth week of treatment. Outcome measures, including the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, Sexual Encounter Profile (SEP), and Traditional Chinese Medicine symptom score, will be evaluated. Discussion: The expected outcome of this trial is that the use of the herbal formula HIJG alone can improve overall sexual satisfaction (OS) in patients with mild to moderate ED, while also improving their traditional Chinese medicine symptom scores. This will provide evidence-based support for the use of Chinese medicine in the treatment of ED in China. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000041127, Registered on 19 December 2020, https://www.chictr.org.cn/showproj.html?proj=46469. Trial Status: Recruitment began in March 2021, therefore 80 patients have been recruited. It is expected to finish recruiting in December 2023.

Selenized glucose improves rat semen quality by improving the gut microbiota and serum metabolome.

Selenium (Se), a well-known antioxidant, is important for male fertility and sperm quality. The gut microbiota is involved in vital activities and cross-talk between reproduction and the gut axis. It is still unclear whether the gut microbiota mediates the impact of selenium on semen quality, and what the underlying mechanisms may be. A selenized glucose (SeGlu) derivative is a novel organic Se compound. After 7 days of acclimation, the Sprague-Dawley (SD) male rats (230 g, 6 weeks) were divided into three drinking groups: deionized water group (CK), SeGlu 0.15 group (0.15 mg Se per L), and SeGlu 0.4 group (0.4 mg Se per L). All animals were euthanized 30 days post-treatment. Serum and intratesticular testosterone and semen parameters were measured. Metagenomic and non-targeted metabolomic approaches were used to study the effects of SeGlu on the gut microbiota and serum metabolites of rats. In both the SeGlu 0.15 Group and the SeGlu 0.4 Group, we found a significant increase in seminiferous epithelium thickness. While the SeGlu 0.4 Group had a tendency to increase with insignificant difference, the SeGlu 0.15 Group significantly improved the sperm viability, survival rate, and seminal plasma fructose. SeGlu had no effect on intratesticular testosterone levels, or abnormal sperm counts. Measured serum testosterone levels using ELISA and LC-MS, which showed a decreasing trend. ELISA did not reveal significant differences, but LC-MS indicated a significant decrease in SeGlu 0.4 group. Meanwhile, the SeGlu 0.15 Group reduced the abundance of harmful bacteria such as Rikenella, Barnesiella, Tenacibaculum, and Aeromonas while increasing the abundance of beneficial microbiota such as Intestinimonas, Christensenella, Coprococcus, and Butyrivibrio. Linear discriminant analysis Effect Size (LEfSe) identified the SeGlu 0.15 group's feature genera as Roseburia, Clostridium, Ruminococcus, and Eubacterium. Serum metabolites showed that the SeGlu 0.15 Group increased 5 beta-androstane-3,17-dione while decreasing estrone and 2-methoxyestradiol (2-MeOE2). In conclusion, the SeGlu 0.15 Group can significantly alter the levels of several sex hormones in serum, improve the quality of rats' sperm, and reduce harmful bacterial colonization. SeGlu 0.15 may be used as an effective dietary supplement.

Expression of lncRNA MALAT1 through miR-144-3p in Osteoporotic Tibial Fracture Rats and Its Effect on Osteogenic Differentiation of BMSC under Traction.

Objective: To investigate the expression of lncRNA MALAT1 and miR-144-3p in osteoporotic (OP) tibial fracture rats and analyze their targeting relationship and effects on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC) under traction. Methods: The OP tibial fracture model was established, and the rats were divided into a sham group and a model group. The tibial tissue of these rats was taken. BMSC of cultured rats with good growth was purchased and grouped according to the presence or absence of transfection of si-MALAT1 and miR-144-3p-mimic. The expression of MALAT1 and miR-144-3p in each group was detected. The bioinformatics website and double luciferase were used to predict the targeting relationship between MALAT1 and miR-144-3p and to detect the expression of genes related to bone differentiation (collagen I, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP)) of each component, and ALP staining and AR staining were used to detect the formation of BMSC calcium nodules. Results: The levels of ALP and TRAP in the model group were higher than that in the sham group (P < 0.05). qRT-PCR results showed that the relative expression level of MALAT1 in the model group was higher than that in the sham group, and the relative expression level of miR-144-3p was lower than that in the sham group (P < 0.05). MALAT1 has a targeting relationship with miR-144-3p. qRT-PCR results showed that the relative expression level of MALAT1 in the tension-MSC group was higher than the MSC group, and the relative expression level of miR-144-3p was lower than the MSC group (P < 0.05). The expressions of collagen I, OCN, OPN, and ALP proteins in the si-MALAT1 group were higher than those of the si-NC group (P < 0.05). The results of ALP staining showed that BMSCs of the si-MALAT1 group had stronger osteogenic differentiation capacity and higher ALP activity than those of the si-NC group. The results of AR staining showed that compared with the si-NC group, the mineralization degree of cells in the si-MALAT1 group was higher, the number of calcium nodules was more, and the cells were more deeply stained. The expressions of collagen I, OCN, OPN, and ALP proteins in the miR-144-3p-mimic group were higher than the mimic-NC group (P < 0.05). ALP staining results showed that BMSCs in the miR-144-3p-mimic group had strong osteogenic differentiation capacity and high ALP activity compared with the mimic-NC group. The results of AR staining showed that, compared with the mimic-NC group, the mineralization degree of cells in the miR-144-3p-mimic group was higher, the number of calcium nodules was more and the cells were more deeply stained. Conclusion: In the OP rat model with the tibial fracture, the expression of MALAT1 is upregulated and that of miR-144-3p is downregulated. MALAT1 has a targeting relationship with miR-144-3p, and downregulation of MALAT1 and upregulation of miR-144-3p can promote the osteogenic differentiation of BMSC under traction.

A Traditional Chinese Medicine for the Treatment of Endometrial Hyperplasia via Regulating the HPO Axis in Rats.

Dysfunctional uterine bleeding, accompanied by endometrial hyperplasia (EH), is a common gynecological disease that seriously affects female physical and mental health. Some drugs have been prompted to cure the disease, but most medications have certain side effects and limitations. In the present study, we demonstrated an unexploited Chinese traditional medicine, a combination of Saururus chinensis, Celosia cristata, and Spatholobus suberectus (SCS), which could be used for the treatment of EH and associated complications in rats. We identified the active components from the three Chinese herbs via thin-layer chromatography and high-performance liquid chromatography methods. In addition, serum biochemical indexes and histologic section results found that acute high-dose SCS exerted no adverse impacts on the rats. We then showed that SCS shortened coagulation time (p=0.018) and degree of swelling (p=0.021) on rats at 30 min compared to blank control. Further studies proved that recovered endometrial thickness was associated with the modulation of four hormones (follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone). Specifically, follicle-stimulating hormone and progesterone contents increased gradually with time, and estrogen was decreased, whereas luteinizing hormone content was returned to normal after a short-term elevation (p < 0.05). Besides, SCS increased uterine endometrium's mRNA expression levels of matrix metalloproteinase-1 (p < 0.001) and tissue inhibitor of matrix metalloproteinase-1 (p < 0.001), promoting the repair of proliferating endometrium in the rats. Collectively, our study indicates that SCS harbors a profoundly curative effect on the treatment of EH and relative complications and uncovers the mechanism at molecular and gene expression levels.

Versatile polarization manipulation in vanadium dioxide-integrated terahertz metamaterial.

Broadband and switchable versatile polarization metamaterial is crucial in the applications of imaging, sensing and communication, especially in the terahertz frequency. Here, we investigated versatile polarization manipulation in a hybrid terahertz metamaterial with bilayer rectangular rods and a complementary vanadium dioxide (VO2) layer. The VO2 phase transition enables a flexible switching from dual-band asymmetric transmission to dual-band reflective half-wave plate. The full width half maximum (FWHM) bandwidths of dual-band asymmetric transmission are 0.77 and 0.21 THz, respectively. The polarization conversion ratio (PCR) of the reflective metamaterial is over 0.9 in the frequency ranges of 1.01-1.17 THz and 1.47-1.95 THz. Angular dependences of multiple polarization properties are studied. The proposed switchable polarization metamaterial is important to the development of multifunctional polarization devices and multichannel polarization detection.

Protective Effects of Total Flavonoids from Lysimachia christinae on Calcium Oxalate-Induced Oxidative Stress in a Renal Cell Line and Renal Tissue.

Oxidative stress (OS) in renal tubular epithelial cells (RTECs) is induced by calcium oxalate (CaOx) stones and plays an important role in the pathology of CaOx nephrolithiasis. The nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important endogenous antioxidant pathway. Flavonoids are compounds with 2-phenylchromone as the basic mother nucleus and are natural antioxidant components of Lysimachia christinae. Our previous studies demonstrated that the total flavonoids from L. christinae (TFL) reduced calcium and oxalic acid concentrations in urine, thus inhibiting CaOx stone formation. We also showed that TFL can reduce OS in renal tissue. However, whether TFL inhibit the formation of CaOx stones through the Nrf2/ARE pathway requires further investigation. Here, we found that TFL protected against injury to a renal cell line and renal tissue, reduced CaOx-induced OS in renal tissue, and reduced CaOx crystal formation. In addition, TFL significantly increased nuclear Nrf2 and the expression of the downstream antioxidant genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). Furthermore, TFL increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content, thereby alleviating OS in RTECs. Silencing Nrf2 expression blocked the protective effect of TFL on CaOx-induced OS. Taken together, our findings indicate that TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway.

O-glycosyltransferases from Homo sapiens contributes to the biosynthesis of Glycyrrhetic Acid 3-O-mono-ß-D-glucuronide and Glycyrrhizin in Saccharomyces cerevisiae.

Glycyrrhizin (GL) and Glycyrrhetic Acid 3-O-mono-ß-D-glucuronide (GAMG) are the typical triterpenoid glycosides found in the root of licorice, a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations. However, only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far. In mammals, glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases. In this study, we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate, glycyrrhetinic acid (GA) for its glycodiversification. Out of 22 selected glycosyltransferases, only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG. Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels (P82~R85) and substrates. Furthermore, the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time, resulting in the production of 5.98 ± 0.47 mg/L and 2.31 ± 0.21 mg/L of GL and GAMG, respectively.

In vivo and in vitro protective effects of the Wuzi Yanzong pill against experimental spermatogenesis disorder by promoting germ cell proliferation and suppressing apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuzi Yanzong pill (WZYZP) is a classical traditional Chinese medicine (TCM) formula originated from the Tang dynasty. WZYZP has a long history of use for reinforcing kidney and alleviating male infertility in China. AIM OF THE STUDY: The effect of WZYZP on male infertility and the mechanism underlying this effect was not clarified clearly. Therefore, this study aimed to investigate the protective effect of WZYZP in experimental spermatogenesis disorder via in vivo and in vitro studies, to promote the use of this formula for the treatment of spermatogenesis disorder. MATERIAL AND METHODS: Male SD rats were exposed to tripterygium glycosides to induce experimental spermatogenesis disorder, and WZYZP was subsequently administrated at different dosages for treatment. Sperm counts, sperm motility, and serum hormone levels were detected. HE staining and TUNEL staining were performed to evaluate the pathological lesions and apoptosis of testes, respectively. Next, germ cells were isolated from spermatogenesis disorder-model rats and treated with WZYZP- containing serum at different concentrations. CCK-8 assay and flow cytometry assay were performed to detect cell proliferation and apoptosis. Immunofluorescence assay, qRT-PCR and Western blotting analyses were performed to detect the expression of Beclin 1, LC3 and TGF-ß-PI3k/AKT-mTOR pathway - related factors, including TGF-ß, PI3K, AKT, mTOR, 4 EBP-1 and p70S6K. RESULTS: In vivo experiments showed that WZYZP protected against spermatogenesis disorder in model rats by improving sperm count and motility, as well as restoring serum hormone levels. HE and TUNEL staining demonstrated that the pathological injuries and cell apoptosis in testes of the model rats were alleviated by WZYZP treatment. Moreover, in vitro experiments of germ cells isolated from spermatogenesis disorder-model rats showed that WZYZP treatment increased the cell proliferation, inhibited cell apoptosis and autophagy. qRT-PCR and Western blotting assay results showed that this protective effect was associated with the regulation of the TGF-ß/PI3K/AKT/mTOR signaling pathway. The expression levels of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, 4 EBP-1 and p70S6K were increased, while TGF-ß was inhibited in the WZYZP treated groups. CONCLUSION: The results showed that WZYZP could protect against experimental spermatogenesis disorder by increasing the germ cell proliferation and inhibiting their apoptosis. Our support the clinical use of this formula for the management of spermatogenesis disorder.

A four-component combination derived from Huang-Qin Decoction significantly enhances anticancer activity of irinotecan.

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index Ei, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo. As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.

Neuroprotective effect of Hongjing I granules on erectile dysfunction in a rat model of bilateral cavernous nerve injury.

Neurogenic erectile dysfunction (NED) is an inevitable postoperative disease of cavernous nerve injury which will lead to various pathophysiological changes in the corpus cavernosum and dorsal penile nerve caused by radical prostatectomy (RP). Although serval years of clinical application of HJIG I granules (HJIG), an innovative formulation, has demonstrated its reliable clinical efficacy against NED, the mechanism of HJIG remains unclear. This study aimed to assess the neuroprotective effect of HJIG, to repair damaged nerves in a rat model of bilateral cavernous nerve injury (BCNI) in vivo and their effects on neurites of major pelvic ganglia (MPG) regeneration and Schwann cells (SCs) proliferation in vitro. Rats were divided into five groups randomly: normal control (NC), BCNI-induced ED model (M), M + low-dose HJIG (HL), M + medium-dose HJIG (HM), and M + high-dose HJIG (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after a standard NED animal model. Our data revealed that administration of HJIG improved NED that was detected by intracavernous pressure (ICP) in a dose-dependent manner. The haematoxylin-eosin (HE) and Immunofluorescence (IF) staining demonstrated that HJIG ameliorate the shape of penis and induced the protein synthesis of GAP43, NF200, S100, and nNOS. NF200 and S100 level were also detected by western blotting. Moreover, HJIG (0.78 mg/mL) markedly increased SCs viability and promoted neurites regeneration of MPG. These findings provide new insights into the NED therapy by HJIG.

Network Pharmacology and Bioactive Equivalence Assessment Integrated Strategy Driven Q-markers Discovery for Da-Cheng-Qi Decoction to Attenuate Intestinal Obstruction.

BACKGROUND: Intestinal obstruction (IO) is a kind of acute abdomen with high morbidity and mortality. Patients suffer from poor quality of life and tremendous financial pressure. Da-Cheng-Qi decoction (DCQD), a classical purgation prescription, has clinically been proven to be an effective treatment for IO. PURPOSE: Network pharmacology integrated with bioactive equivalence assessment was used to discover the quality marker (Q-marker) of DCQD against IO. METHODS: As there is hardly any targets recorded in database, thus the collection of IO targets was conducted by searching those of alternative diseases which have similar pathological symptoms with IO. In order to improve the reliability of the obtained targets, IO metabolomics data was introduced. Active compounds combination (ACC) was focused as potential Q-markers via component-target network analysis and function query from the identified components corresponding to the common targets. Bioequivalence between ACC and DCQD was assessed from the aspects of intestine motility (somatostatin secretion), inflammation (IL-6 secretion) and injury (wound healing assay) in vitro and was further validated in ileus rat model. PPI network analysis of core targets followed by gene pedigree classification and experimental validation confirmed the potential intervention pathway. RESULTS: A combination of 11 ingredients, including emodin, physcion, aloe-emodin, rhein, chrysophanol, gallic acid, magnolol, honokiol, naringenin, tangeretin, and nobiletin was finally confirmed bioequivalence with DQCD to some extent and could serve as Q-markers for DCQD to attenuate IO. PI3K/AKT was verified as a possible affected pathway that DCQD exerted the effectiveness against IO. CONCLUSION: For the disease with few recorded targets, searching those of alternative diseases which have similar pathological symptoms could be a feasible and effective approach. The proposed network pharmacology integrated bioactive equivalence evaluation paradigm is efficient to discover Q-marker of herbal formulae.

Tong-fu-li-fei decoction exerts a protective effect on intestinal barrier of sepsis in rats through upregulating ZO-1/occludin/claudin-1 expression.

Tong-fu-li-fei (TFL) prescription has already used to treat sepsis in clinic but its mechanism remains unclear. Here, we aimed to investigate the effect and mechanism of Tong-fu-li-fei (TFL) prescription on sepsis in rats. The Sprague-Dawley rats were divided into the sham group, model group, the TFL 3.6 g/kg and 7.2 g/kg-treated group. The sepsis model was induced by cecal ligation and puncture (CLP). After 7 days, TFL treatment improved the survival rate of CLP rats and alleviated sepsis-induced intestinal mucosal injury. The ELISA assay showed that inflammatory cytokine expressions including TNF-α and IL-1ß in serum from TFL-treated rats were lower than that in the model. And TNF-α, IL-1ß and IL-6 from intestinal tissues were also decreased and IL-10 was increased in TFL-treated rats. Meanwhile the expression levels of the tight junction molecules occludin, claudin-1, and zonula occludens-1 (ZO-1) mRNA and protein expressions examined by RT-PCR, western blot and immunohistochemistry, were also restored in rats that received TFL treatment. Our data showed that TFL mitigates the inflammatory response and maintains intestinal barrier function in sepsis through upregulating ZO-1/occludin/claudin-1 expression, providing a good experimental basis for its clinical treatment of sepsis.

Simo decoction versus domperidone suspension for post-pyloric spiral nasoenteric tube placement: A multicenter, randomized, non-inferiority trial.

BACKGROUND & AIMS: Leveraging prokinetics to facilitate trans-pyloric migration is a conventional strategy. However, due to restrictions on the use of domperidone suspension, oral prokinetics is relatively modest. The study aims to assess the effectiveness of simo decoction as an alternative to domperidone suspension in facilitating post-pyloric placement of spiral nasoenteric tubes. METHODS: A prospective, open-label, parallel, and non-inferiority randomized controlled trial was performed involving critically ill adults in 6 university hospitals in China between September 2017 and May 2019. Patients were randomly assigned to receive either simo decoction 20 ml q8h, or domperidone suspension 20 mg/20 ml q6h for 24 h. The primary outcome was procedure success defined as post-pyloric placement (spiral nasoenteric tubes reached the first portion of the duodenum or beyond confirmed by abdominal X-ray 24 h after tube insertion). RESULTS: Of 268 patients assessed for eligibility, 224 patients were enrolled and randomly assigned to the simo decoction group or the domperidone suspension group (n = 112 per group). The success rate of post-pyloric placement was 41.1% (46/112) in the simo decoction group, as compared with 47.3% (53/112) in the domperidone suspension group (a risk difference of -6.3%, 95% CI, -19.2% to 6.7%, adjusted risk difference -3.7%, 95% CI -16.3% to 9.0%), in the intention-to-treat analysis, crossing the prespecified margin of -10% for non-inferiority. There were no differences between groups in the success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond) and proximal jejunum placement, the incidences of any adverse events, length of ICU stay or mortality in ICU. CONCLUSIONS: Non-inferiority of simo decoction to domperidone suspension was not confirmed in facilitating post-pyloric placement of spiral nasoenteric tubes. Registration: The trial was registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn (registration number ChiCTR-INR-17011311).

The ameliorating effects of Bushen Tiaoxue Granules and Kunling Wan on impaired angiogenesis and endometrial receptivity in rats following controlled ovarian hyperstimulation.

OBJECTIVE: To investigate the effects of Bushen Tiaoxue Granules and Kunling Wan, the two Chinese medicines, on vascular dysfunction and the impairment of endometrial receptivity caused by controlled ovarian hyperstimulation and its underlying mechanism. METHODS: Female Sprague Dawley rats with regular estrous cycle were enrolled and given Bushen Tiaoxue Granules or Kunling Wan by gavage for 12 days, and then, controlled ovarian hyperstimulation model was induced. We assessed endometrial microvessels, endometrial blood flow, levels of estradiol and progesterone in serum, vascular endothelial growth factor A upstream molecules estrogen and progesterone receptors in the endometrium, and pregnancy outcome. RESULTS: Pre-treatment of Bushen Tiaoxue Granules or Kunling Wan increases endometrial blood flow of controlled ovarian hyperstimulation rats, up-regulates vascular endothelial growth factor A and microvessels, improves the endometrial morphology of controlled ovarian hyperstimulation rats during implantation, decreases the super physiological concentration of estradiol and progesterone in serum, and increases the expression of vascular endothelial growth factor A upstream molecules estrogen and progesterone receptors in the endometrium. In addition, Bushen Tiaoxue Granules or Kunling Wan elevates the lysophosphatidic acid receptor 3 that participates in vascularization and increases the expression of leukemia inhibitory factor through up-regulating the expression of p53 in the endometrium, ultimately affecting pregnancy outcome. CONCLUSION: This study demonstrated Bushen Tiaoxue Granules or Kunling Wan as a potential strategy for prevention of impairment in angiogenesis and endometrial receptivity induced by controlled ovarian hyperstimulation.

Effect of HongJing I in Treating Erectile Function and Regulating RhoA Pathway in a Rat Model of Bilateral Cavernous Nerve Injury.

HongJing I (HJI), a traditional Chinese herbal formula, has been confirmed to be effective for the clinical treatment of erectile dysfunction (ED). However, the mechanism of action of HJI remains unclear. Here, we aimed to investigate the effect and underlying mechanisms of HJI against ED in a rat model of bilateral cavernous nerve injury (BCNI). Rats were divided into five groups: normal control (NC), BCNI-induced ED model (M), M + low-dose HJI (HL), M + medium-dose HJI (HM), and M + high-dose HJI (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after inducing BCNI-ED. At the end of the treatment period, the intracavernous pressure (ICP) was recorded, and histological examination was conducted using Masson's trichrome staining. Immunofluorescence staining and western blotting were applied to detect the changes in fibrosis protein and Ras homolog A (RhoA), Rho-associated protein kinase 1 (ROCK1), and ROCK2 expression. We found that HJI effectively improved the ICP in the treatment groups. In addition, RhoA, ROCK1, and ROCK2 expression levels were increased upon BCNI-ED induction, and HJI successfully inhibited cavernosum fibrosis and the activation of RhoA/ROCK2 signaling. Overall, these results suggest that the effects of HJI in attenuating ED may be caused, at least in part, by the suppression of RhoA/ROCK2 signaling and alleviation of fibrosis. However, the precise mechanism surrounding this requires further investigation in future studies.

Impact of family integrated care on infants' clinical outcomes in two children's hospitals in China: a pre-post intervention study.

BACKGROUND: Most Neonatal Intensive Care Units (NICUs) in China have restricted visiting policies for parents. This also implicates that parents are not involved in the care of their infant. Family Integrated Care (FIC), empowering parents in direct care delivery and decisions, is becoming the standard in NICUs in many countries and can improve quality-of-life and health outcomes of preterm infants. The aim of this study was to evaluate the impact of a FIC intervention on the clinical outcomes of preterm infants with Bronchopulmonary Dysplasia (BPD). METHODS: A pre-post intervention study was conducted at NICUs in two Chinese children's hospitals. Infants with BPD were included: pre-intervention group (n = 134) from December 2015 to September 2016, post-intervention (FIC) group (n = 115) and their parents from October 2016 to June 2017. NICU nurses were trained between July and September 2016 to deliver the FIC intervention, including parent education and support. Parents had to be present and care for their infant minimal three hours a day. The infants' outcome measures were length-of-stay, breastfeeding, weight gain, respiratory and oxygen support, and parent hospital expenses. RESULTS: Compared with control group (n = 134), the FIC group (n = 115) had significantly increased breastfeeding rates (83% versus 71%, p = 0.030), breastfeeding time (31 days versus 19 days, p < 0.001), enteral nutrition time (50 days versus 34 days, p < 0.001), weight gain (29 g/day versus 23 g/day, p = 0.002), and significantly lower respiratory support time (16 days versus 25 days, p < 0.001). Oxygen Exposure Time decreased but not significant (39 days versus 41 days p = 0.393). Parents hospital expenses in local Chinese RMB currency was not significant (84 K versus 88 K, p = 0.391). CONCLUSION: The results of our study suggests that FIC is feasible in two Chinese NICUs and might improve clinical outcomes of preterm infants with BPD. Further research is needed to include all infants admitted to NICUs and should include parent reported outcome measures. Our study may help other NICUs with limited parental access to implement FIC to enhance parental empowerment and involvement in the care of their infant.