Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

INTRODUCTION: Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that ß-hydroxy ß-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. METHODS AND ANALYSIS: In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. ETHICS AND DISSEMINATION: This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences. TRIAL REGISTRATION NUMBER: NCT05525039.

Moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle-aged and elderly female patients with hypertension.

To explore the moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle-aged and elderly female patients with hypertension and provide a foundation for the development of more effective mindfulness intervention strategies. A total of 109 middle-aged and elderly female patients with hypertension participated in this cross-sectional study from April to July 2022 and provided valid responses to the Five Facet Mindfulness Questionnaire (FFMQ), the Hospital Anxiety and Depression Scale (HADS), and the Somatization Symptom Self-rating Scale (SSS). The moderating effect of mindfulness was determined using multiple linear regression. The participants' average scores were as follows: mindfulness: 123.86 ± 10.49; anxiety: 7.41 ± 3.62; and somatization symptoms: 41.2 ± 9.44. The anxiety (P = .000) and somatization symptoms (P = .001) of participants with high mindfulness were significantly reduced. Anxiety was positively correlated with somatization symptoms (r = 0.606, P = .000), while mindfulness was negatively correlated with both anxiety (r = -0.468, P = .000) and somatization symptoms (r = -0.439, P = .000). Moreover, mindfulness had a significant moderating effect on the relationship between anxiety and somatization symptoms (n = 109) (B = -0.166, t = -2.125, P = .036). The effect of mindfulness on anxiety and somatization symptoms was more significant in participants with low mindfulness levels (n = 56) (B = 0.144, t = 2.805, P = .008) than in participants with high mindfulness levels (n = 53) (B = -0.037, t = -0.864, P = .393). The moderating effect analysis based on regression analysis showed that mindfulness had a significant moderating effect on anxiety and somatization symptoms, especially in participants with low mindfulness levels.

Treatment of Elderly Femoral Intertrochanteric Fracture by InterTan Intramedullary Nail and PFNA.

To analyze the treatment of elderly femoral intertrochanteric fracture (EFIF) using InterTan intramedullary nail (InterTanIN) and proximal femoral nail antirotation (PFNA). A total of 75 patients suffering from EFIF receiving intramedullary fixation were retrospectively collected. According to intramedullary fixation methods, the patients were separated into InterTanIN group and PFNA group. Parameters including the surgery time, blood loss, number of X-ray fluoroscopy, hospital stays, bone-healing time, postoperative Harris hip score (HIS) (1 month, 3 months, 6 months, and 12 months), and complications were collected and analyzed. The results showed surgery time, blood loss, and number of X-ray fluoroscopy in InterTanIN group were higher than those in PFNA group (P < 0.05). The mean hospital stay in the InterTanIN group was comparable to that in the PFNA group (P > 0.05). There was no significant difference in bone-healing time between the InterTanIN group and PFNA group (P > 0.05). The postoperative HIS of InterTanIN group was statistically better than PFNA group at the 3rd month and the 6th month (P < 0.05). With the extension of recovery time, the gap between the two groups gradually narrowed. The postoperative implant displacement happened more often in the PFNA group than in the InterTanIN group. EFIF treated with InterTanIN or PFNA could achieve good long-term efficacy. Although InterTanIN has the disadvantages of increased operative time, blood loss, and radiation exposure compared to PFNA, the postoperative hip function recovery of InterTanIN seems to be more reliable and stable than PFNA.

Simultaneous adsorption-photocatalytic treatment with TiO2-Sep nanocomposites for in situ remediation of sodium pentachlorophenol contaminated aqueous and soil.

Sodium pentachlorophenol (NaPCP) is a highly toxic and persistent organic pollutant. With sepiolite as the support, a series of TiO2-Sep nanocomposites (NCs) with different Ti/Sep ratios were developed. The objective was to understand the effect of Ti/Sep ratio on the structure and activity of the NCs in aqueous and soil systems and to evaluate the feasibility of the NCs for in situ soil remediation. The prepared NCs were characterized with XRD, SEM, TEM, and N2 adsorption-desorption, respectively. The results showed that high surface area and good dispersion of TiO2 on sepiolite surface were obtained. The photocatalytic activities in aqueous and soil of the as-developed NCs were examined using NaPCP as a model pollutant. Compared with bare sepiolite and TiO2, the heterogeneous NCs showed significantly higher photocatalytic performance in decomposing NaPCP, and the photocatalytic activities varied with the content of TiO2 in the NCs. In aqueous media, treatment with TiO2-S-30 showed excellent degradation efficiency with about 90% NaPCP decomposed in 140 min. Nevertheless, the sample TiO2-S-20 promotes maximum rate reduction of NaPCP with above 90% within 20-h irradiation in soil. The results indicate that an appropriate Ti/Sep ratio could significantly enhance the activities of NCs on NaPCP remediation and the role of carrier sepiolite is more important in soil media than that in aqueous phase. The excellent performance of the TiO2-Sep in wastewater degradation and soil remediation can be attributed to the synergistic effects between the high photocatalytic activity of TiO2 nanoparticles and the strong adsorption capacity of sepiolite nanofibers. This work revealed that sepiolite adsorption coupled with TiO2 photocatalysis can be one promising technique for in situ remediation of NaPCP-contaminated soil.

Utilizing network pharmacology and experimental validation to explore the potential molecular mechanisms of BanXia-YiYiRen in treating insomnia.

BanXia-YiYiRen (Pinellia Ternata and Coix Seed, BX-YYR) has been clinically proven to be an effective Chinese medicine compatible with the treatment of insomnia. However, the underlying mechanism of BX-YYR against insomnia remains unclear. This study aimed to explore the pharmacological mechanisms of BX-YYR in treating insomnia based on network pharmacology and experimental validation. The drug-disease targets were obtained using publicly available databases. The analysis revealed 21 active compounds and 101 potential targets of BX-YYR from the pharmacological database of Chinese medicine system and analysis platform (TCMSP) and 1020 related targets of insomnia from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Furthermore, 38 common targets of BX-YYR against insomnia were identified, and these common targets were used to construct a protein-protein interaction (PPI) network. The visual PPI network was constructed by Cytoscape software. The top three genes from PPI according to degree value are FOS, AKT1, and CASP3. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were applied to reveal the potential targets and signaling pathways involved in BX-YYR against insomnia, especially the serotonergic pathway. In addition, molecular docking revealed that baicalein, beta-sitosterol, and stigmasterol displayed strong binding to AKT1, FOS, PRKCA, and VEGFA. Experimental study found that BX-YYR against insomnia might play a role in improving sleep by modulating the serotonergic pathway. In summary, our findings revealed the underlying mechanism of BX-YYR against insomnia and provided an objective basis for further experimental study and clinical application.

Separation of Three Phenanthrenes and Two Bibenzyls from Chloroform Fractions of Pholidota Articulata Lindl. Using HPLC.

BACKGROUND: Pholidota articulata Lindl has been used as a traditional medicine and Yi-nationality herbal medicine for the treatment of various diseases. Phenanthrenes and bibenzyls commonly found in the genus Pholidota are one of their most important natural ingredients, due to their various biological activities. OBJECTIVE: This study aimed to establish an HPLC method for determination of the levels of three phenenthrenes (flavidin, lusianthridin, coelonin) and two bibenzyls (batatasin III, cirrhopetalidin) in rhizomes of P. articulata Lindl. METHOD: The separated and elucidated compounds from chloroform fractions of P. articulata Lindl were used as standards and analyzed by gradient elution HPLC with a variable wavelength detector at 274 nm. RESULTS: The calibration curves exhibited good linearity (R2 = 0.9999), ranging from 20 to 960 ng/mL, the average recoveries were between 91.5 and 102.9%, and the RSD values of precision, stability, and repeatability were <2.34%. There were significant differences in the content of phenenthrenes and bibenzyls from the plants of genus Pholidota, Dendrobium, and Bulbophyllum. Furthermore, this is the first report on the validation of a method for the quantitative analysis of flavidin and cirrhopetalidin. CONCLUSIONS: The present study provides an alternative method for the rapid separation of phenanthrenes and bibenzyls from natural products and lays a foundation for the study of biological activity. HIGHLIGHTS: When using developed method in this study for separation of phenanthrenes and bibenzyls in genus Pholidota, chemicalin formation was more abundant from chloroform fractions.

Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis.

Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.

Chinese midwives' perceptions on upright positions during the second stage of labour: A qualitative study.

OBJECTIVE: Upright positions are recommended by many international organizations due to their positive effects on improving birth outcomes. The effects can only be achieved when upright positions are properly adopted by women under the guidance of midwives. However, whether midwives in China have a clear understanding of upright positions during the second stage of labour is an issue that has not been explored. The aim of this study was to explore midwives' perceptions on assisting women in upright positions during the second stage of labour in the context of China. DESIGN: A qualitative descriptive design was adopted. We analysed the data using the conventional content analysis and reported the study in line with the COREQ checklist. SETTING: The study was conducted at the labour wards of two maternity hospitals and two general hospitals in China where the adoption of upright positions was encouraged during the second stage of labour. PARTICIPANTS: Semi-structured individual interviews with 17 midwives were conducted between May and July 2020. FINDINGS: Three main themes were identified: (1) safety and availability; (2) unclear method of implementation; (3) lack of knowledge of the potential risks and precautions. Midwives' perceptions were based primarily on clinical experience rather than evidence-based practice. Their perceptions on the indications and contraindications of upright positions were divergent and ambiguous. Midwives' suggested that the indications and contraindications should be adjusted in the context of China. Time limit for keeping an upright position and maternal pushing during uterine contractions were two questions that still confused midwives. Midwives lacked knowledge of the potential risks of upright positions and rarely systematically summarized the precautions. KEY CONCLUSIONS: This study shows that assisting women to give birth in upright positions during the second stage of labour can be a challenge for midwives in China, and also highlights the need for clarifying the detailed implementation methods of upright positions in the context of China by evidence-based approaches. IMPLICATIONS FOR PRACTICE: An evidence-based protocol for implementing upright positions during the second stage of labour should be developed to guide midwives' practice and facilitate the successful use of upright positions in China.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Four new phenanthrene derivatives from Bulbophyllum retusiusculum.

Three new dihydrophenanthrenes, retusiusine D (1), retusiusine E (2), retusiusine F (3), and a new phenanthrene retusiusine G (4), together with two known dihydrophenanthrenes 4,7-dihydroxy-2,3-methylenedioxy-9,10-dihydrophenanthrene (5) and epemeranthol-A (6) were isolated from the tubers of Bulbophyllum retusiusculum. Their structures were established on the basis of extensive spectroscopic analyses. Compounds 1 and 2 exhibited potent cytotoxic activities against SMMC-7721 and weak cytotoxic activities against HL-60. Compound 4 showed moderate cytotoxic activity against SMMC-7721 and MCF-7.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System.

OBJECTIVE: To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). METHODS: Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. RESULTS: Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. CONCLUSIONS: TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

Gold nanoparticle-modified black phosphorus nanosheets with improved stability for detection of circulating tumor cells.

Gold nanoparticle (AuNP)-anchored BP nanosheets were synthesized through in situ growth of AuNPs onto BP. Due to the strong chelating ability of P or phosphorus oxides with AuNPs, the stability of BP is improved. As proof-of-concept demonstration of the functionalized BP, electrochemical detection of circulating tumor cells (CTCs) based on BP@AuNPs@aptamer as a probe combined with immunomagnetic separation is reported. The aptamer can specifically bind with CTCs, while the phosphorus oxides including phosphite ion and phosphate ion (PxOy species) on BP and aptamer can react with molybdate to generate an electrochemical current, leading to dual signal amplification. The biosensor is applied to MCF-7 cell detection and displays good analytical performance with a detection limit of 2 cell mL-1. Furthermore, the practicality of this biosensor was validated through sensitive determination of MCF-7 cells in human blood. Therefore, the reported biosensor could be applied to detect other biomarkers, offering an ultrasensitive strategy for clinical diagnostics. Graphical abstract Electrochemical detection of circulating tumor cells based on gold nanoparticle-modified black phosphorus nanosheets is reported.

Early Intervention of Tongxinluo () on Right Ventricular Function Assessed by Echocardiography in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline.

OBJECTIVE: To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). METHODS: A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes. RESULTS: MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices. CONCLUSION: Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.

Aanat Knockdown and Melatonin Supplementation in Embryo Development: Involvement of Mitochondrial Function and DNA Methylation.

Aims: In addition to pineal gland, many cells, tissues, and organs also synthesize melatonin (N-acetyl-5-methoxytryptamine). Embryos are a group of special cells and whether they can synthesize melatonin is still an open question. However, melatonin application promoted embryo development in many species in in vitro condition. The purpose of this study was to investigate whether embryos can synthesize melatonin; if it is so, what are the impacts of the endogenously produced melatonin on embryo development and the associated molecular mechanisms. These have never been reported previously. Results: Melatonin synthesis was observed at different stages of embryonic development. Aanat (aralkylamine N-acetyltransferase), a rate-limiting enzyme for melatonin production, was found to mostly localize in the mitochondria. Aanat knockdown significantly impeded embryonic development, and melatonin supplementation rescued it. The potential mechanisms might be that melatonin preserved mitochondrial intact and its function, thus providing sufficient adenosine 5'-triphosphate for the embryo development. In addition, melatonin scavenged intracellular reactive oxygen species (ROS) and reduced the DNA mutation induced by oxidative stress. In the molecular level, Aanat knockdown reduced tet methylcytosine dioxygenase 2 (Tet2) expression and DNA demethylation in blastocyst and melatonin supplementation rescued these processes. Innovation: This is the first report to show that embryos synthesize melatonin, and its synthetic enzyme Aanat was located in the mitochondria of embryos. An effect of melatonin is to maintain Tet2 expression and normal methylation status, and thereby promote embryonic development. Conclusion: Embryos can produce melatonin that reduces ROS production, preserves mitochondrial function, and maintains Tet2 expression and the normal DNA methylation.

Preventive effect of Tongxinluo on endothelial survival and vascular integrity, together with inhibition of inflammatory reaction in rats model of intestine ischemia/reperfusion injury.

This study was design to investigate preventive function of Tongxinluo (TXL) capsule on micro vascular function and endothelial survival in rats model of intestine ischemia/reperfusion (I/R) injury. We randomly divided fifty male Sprague-Dawley rats into Sham group, I/R group, TXL0.4+I/R group, TXL0.8+I/R group, TXL1.6+I/R group (10 rats each). Rat intestine I/R injury was carried out using a model of acute superior mesenteric artery occlusion with 30 min ischemia followed by 60 min reperfusion. The distribution of endothelial apoptosis in intestine was determined by CD31+TUNEL immunofluorescent double staining analysis. VE-Cadherin, ANGPTL4, HMGB1 and NF-κB were determined by immunohistochemical analysis. I/R induced massively endothelial cell apoptosis, accompanied with reduced expression of adherens junction protein VE-Cadherin and up regulation of inflammatory mediator HMGB1 and NF-κB. TXL pretreatment groups (TXL0.4+I/R, TXL0.8+I/R and TXL1.6+I/R group) significantly attenuated endothelial cell apoptosis with a dose-dependent effect. TXL pretreatment could maintain the expression of VE-Cadherin and promote the expression of ANGPTL4 which help to maintain endothelial integrity. TXL pretreatment also exert great influence in inhibiting HMGB1 expression and NF-κB expression induced by I/R. It could be concluded from this study that micro vascular dysfunction and endothelial damage play a causal role in rat intestine I/R injury. TXL pretreatment could significantly prevent the I/R induced pathology of endothelial apoptosis, micro vascular integrity disruption and inflammatory reaction.

New phenylpropanoids from Bulbophyllum retusiusculum.

Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum. The absolute configurations of the new compounds were determined by calculating their electronic circular dichroism (ECD), spectra and specific optical rotations and comparing the calculated values with the experimental data. Compound 2 exhibited potent antifungal activity against Candida albicans (16 µg/mL). Compound 3 showed moderate antibacterial activity against Bacillus subtilis (64 µg/mL).

HEMORHEOLOGY INDEX CHANGES IN A RAT ACUTE BLOOD STASIS MODEL: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Blood stasis has received increasing attention in research related to traditional Chinese medicine (TCM) and integrative Chinese and Western medicine. More than 90% of research studies use hemorheology indexes to evaluate the establishment of animal blood stasis models rather than pathological methods, as hemorheology index evaluations of blood stasis were short of the consolidated standard. The aim of this study was to evaluate the accuracy of hemorheology indexes in rat models of acute blood stasis (ABS) based on studies in which the ABS model had been confirmed by pathological methods. MATERIALS AND METHODS: We searched the Chinese National Knowledge Infrastructure database (CNKI), Chinese Medical Journal Database (CMJD), Chinese Biology Medicine disc (CBM), Wanfang database, and PubMed for studies of rat blood stasis models; the search identified 18 studies of rat ABS models induced by subcutaneous injection of epinephrine combined with an ice bath. Each included study received a modified Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) score list and methodological quality assessment, then data related to whole blood viscosity, plasma viscosity, platelet aggregation rate, erythrocyte aggregation index, and fibrinogen concentration were extracted. Extracted data were analyzed using Revman 5.3; heterogeneity was tested using Egger's test. RESULTS: A total of 343 studies of rat blood stasis were reviewed. Eighteen studies were included in this meta-analysis; the mean CAMARADES score was 3.5. The rat ABS model revealed a significant increase in whole blood viscosity (medium shear rate), whole blood viscosity (high shear rate), plasma viscosity, platelet aggregation rate, erythrocyte aggregation index, and fibrinogen concentration compared to controls, with weighted mean differences (WMD) of 2.42 mPa/s (95% confidence interval (CI) = 1.73 - 3.10); 1.76 mPa/s (95% CI = 1.28 - 2.24); 0.39 mPa/s (95% CI = 0.24 - 0.55); 13.66% (95% CI = 9.78 - 17.55); 0.84 (95% CI = 0.53 - 1.16); and 1.22 g/L (95% CI = 0.76 - 1.67), respectively. Subgroup analysis showed that whole blood viscosity, plasma viscosity, and the platelet aggregation rate test methods were more sensitive when measured at 0-24 h than at 24-72 h after induction of blood stasis. CONCLUSIONS: Rat blood stasis studies have incomplete experimental design and quality controls, and thus need an integrated improvement. Meta-analysis of included studies indicated that the unified hemorheology index of whole blood viscosity (medium and high shear rate), platelet aggregation rate, erythrocyte aggregation rate, and fibrinogen concentration might be used for assessment of rat ABS models independent of pathology methods.

Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol.

Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells.

Changes in nitric oxide, angiotensin â ¡ angiopoietin-like protein 4 mRNA, neuregulin 1 mRNA, and platelet endothelial cell adhesion molecule-1 in rats with acute blood stasis induced by high-molecular-weight dextran.

OBJECTIVE: To investigate the influence of acute blood stasis on nitric oxide (NO), angiotensin Ⅱ(AngⅡ), angiopoietin-like protein 4 (ANGPTL4) mRNA, neuregulin 1 (NRG-1) mRNA, and platelet endothelial cell adhesion molecule-1 (PECAM-1) in rats with stasis induced by high-molecular-weight dextran (HMWD). METHODS: Seventy-five Sprague Dawley rats were divided randomly into five groups (n = 15 in each group): control group, immediate group, 1 h group, 3 h group, and 6 h group. A model of acute blood stasis was established via injection of HMWD into the tail vein. After performing electrocardiogram at the predetermined times according to the grouping, we collected blood and cardiac samples for hematoxylin-eosin (HE) staining and histopathological examination via transmission electron microscopy. Enzyme-linked immunosorbent assay was used to detect plasma levels of NO, AngⅡ, and fibrinogen. Real-time polymerase chain reaction was used to detect the expression of ANGPTL4 mRNA and NRG-1 mRNA. Immunohistochemical methods were used to detect PECAM-1 protein expression. RESULTS: The rat model of blood stasis showed blood retention in the capillary lumens. The ST segment showed gradual elevation, and was still elevated at 3 and 6 h after induction of blood stasis. HE staining showed myocardial cell necrosis and dissolution after modeling, along with basement membrane rupture and mitochondrial structural damage. Transmission electron microscopy showed endothelial cell swelling and an increase in absorption vesicles immediately after modeling. Endothelial cell apoptosis was increased at 3 and 6 h after modeling. Cardiac muscle fibers were disordered and intercalated discs were blurred immediately after modeling. There were massive numbers of dissolved cardiac muscle fibers, ruptured basement membranes, and mitochondrial structural damage at 3 and 6 h after modeling. NO plasma concentration was significantly reduced immediately and 1 h after modeling, while it was increased at 3 and 6 h. Ang¢ò plasma concentration was decreased immediately after modeling, but increased at 1, 3, and 6 h. Fibrinogen plasma concentration was significantly increased at immediate, 1, 3, and 6 h after modeling. PECAM-1 protein expression was obviously increased immediately after modeling, at 1, 6 h was found mild augment. Expression of AngPTL4 mRNA was increased at immediate, 1, 3, and 6 h after modeling, and was found further augment at 3, and 6 h. Expression of NRG-1 mRNA was increased at immediate, 1, 3, and 6 h after modeling, and the strongest expression was at 1 h. CONCLUSION: The pathological manifestation of acute blood stasis is characterized by microvascular blood retention. Prolonged blood stasis leads to worsening endothelial cell and cardiomyocyte damage, along with imbalances in the expression of vasomotor factors and increased vascular tone. The pathological damage caused by blood stasis also promotes the expression of cell protection factors.