Stability of tryptophan-containing LOs in flaxseed oil and their response towards γ-tocopherol.

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.

Rapid Determination of Positive-Negative Bacterial Infection Based on Micro-Hyperspectral Technology.

To meet the demand for rapid bacterial detection in clinical practice, this study proposed a joint determination model based on spectral database matching combined with a deep learning model for the determination of positive-negative bacterial infection in directly smeared urine samples. Based on a dataset of 8124 urine samples, a standard hyperspectral database of common bacteria and impurities was established. This database, combined with an automated single-target extraction, was used to perform spectral matching for single bacterial targets in directly smeared data. To address the multi-scale features and the need for the rapid analysis of directly smeared data, a multi-scale buffered convolutional neural network, MBNet, was introduced, which included three convolutional combination units and four buffer units to extract the spectral features of directly smeared data from different dimensions. The focus was on studying the differences in spectral features between positive and negative bacterial infection, as well as the temporal correlation between positive-negative determination and short-term cultivation. The experimental results demonstrate that the joint determination model achieved an accuracy of 97.29%, a Positive Predictive Value (PPV) of 97.17%, and a Negative Predictive Value (NPV) of 97.60% in the directly smeared urine dataset. This result outperformed the single MBNet model, indicating the effectiveness of the multi-scale buffered architecture for global and large-scale features of directly smeared data, as well as the high sensitivity of spectral database matching for single bacterial targets. The rapid determination solution of the whole process, which combines directly smeared sample preparation, joint determination model, and software analysis integration, can provide a preliminary report of bacterial infection within 10 min, and it is expected to become a powerful supplement to the existing technologies of rapid bacterial detection.

Vitamin D alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism.

Background: Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrition, Vitamin D (VD) plays an important role in regulating gut microbiota based on its receptor (Vitamin D Receptor, VDR) which is highly expressed in the gastrointestinal tract. Methods: Rats were fed with HFD (high-fat diet) for 12 weeks. And the rats were treated with VD two times a week by intraperitoneal injection for 12 weeks. H&E staining combined with plasma biochemical index was performed to characterize pathological changes and function of the liver. Fecal microbiota 16S rRNA gene sequencing and metabolomics were taken to reveal the altered gut microbiota and metabolites. Result: The VD alleviates the HFD-induced lipid accumulation in the liver as well as decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, arginosuccinate, and serine, respectively. Conclusion: VD treatment inhibited HFD-induced NAFLD accompany by dysbiosis gut microbiota and metabolites, suggesting that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.

Biosurfactant promoted enzymatic saccharification of alkali­pretreated reed straw.

The decrease of cellulase activity and unproductive adsorption of lignin are important obstructive factors for inefficient enzymatic hydrolysis. This paper applied five different kinds of biosurfactants including rhamnolipid, sophorolipid, chitin, tea saponin, and sodium lignosulfonate in the enzymatic hydrolysis process of alkali-pretreated reed straw (RS) to enhance the saccharification efficiency. When 8 g/L sophorolipid is added, the efficiency of enzymatic hydrolysis is 91.68 %, which is 30.65 % higher than that without using any biosurfactant. The efficiency of enzymatic hydrolysis can be further increased to 99.56 % when 7.5 g/L sophorolipid and 1.5 g/L tea saponin are added together. This is because the sophorolipid, rhamnolipid, and chitin can synergistically hamper the enzymatic inactivation during enzymatic hydrolysis, while tea saponin and sodium lignosulfonate can inhibit the non-productive adsorption of lignin. This work proposed a very effective method to improve the efficiency of enzymatic hydrolysis and reduce the dosage of the enzyme by adding biosurfactants.

Fluorination Enhances NIR-II Emission and Photothermal Conversion Efficiency of Phototheranostic Agents for Imaging-Guided Cancer Therapy.

Phototheranostics with second near-infrared (NIR-II) imaging and photothermal effect have become a burgeoning biotechnology for tumor diagnosis and precise treatment. As important parameters of phototheranostic agents (PTAs), fluorescence quantum yield (QY) and photothermal conversion efficiency (PCE) are usually considered as a pair of contradictions that is difficult to be simultaneously enhanced. Herein, a fluorination strategy for designing A-D-A type PTAs with synchronously improved QY and PCE is proposed. Experimental results show that the molar extinction coefficient (ε), NIR-II QY, and PCE of all fluorinated PTAs nanoparticles (NPs) are definitely improved compared with the chlorinated counterparts. Theoretical calculation results demonstrate that fluorination can maximize the electrostatic potential difference by virtue of the high electronegativity of fluorine, which may increase intra/intermolecular D-A interactions, tighten molecule packing, and further promote the increase of ε, ultimately leading to simultaneously enhanced QY and PCE. In these PTA NPs, FY6-NPs display NIR-II emission extended to 1400 nm with the highest NIR-II QY (4.2%) and PCE (80%). These features make FY6-NPs perform well in high-resolution imaging of vasculature and NIR-II imaging-guided photothermal therapy (PTT) of tumors. This study develops a valuable guideline for constructing NIR-II organic PTAs with high performance.

Investigating the Metabolic Level of Endogenous and Exogenous Substances on the Intervention of Traditional Chinese Medicine Fuzheng Yiliu Decoction in a Rat Orthotopic Liver Cancer Model.

Background: Fuzheng Yiliu decoction (FZYLD), a Chinese formula consisting of four herbs, can be clinically used as an adjuvant therapy after surgery or palliative treatment for advanced liver cancer. Methods: This study identified the endogenous and exogenous metabolites of FZYLD in rat serum to characterize the underlying mechanism of its antitumor activity, as well as relieving cancer-related weakness. An orthotopic transplantation rat model of HepG2 cells was established and administered with FZYLD by gastric perfusion for 14 days. Cardiopulmonary function and tail suspension test were used to evaluate the bodily weakness of hepatocellular carcinoma (HCC) rats. Tumor weight and size were measured to calculate inhibition ratios. Serum of different concentrations of FZYLD was used to culture the 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose-labeled HepG2 cells. IC50 value was measured using MTT assay. Endogenous and exogenous metabolites in rat serum were detected using nuclear magnetic resonance or LC-MS/MS spectroscopy. Results: FZYLD improved cardiopulmonary function, decreased immobility time in tail suspension test, and yielded tumor inhibition ratios of up to 27%. Serum endogenous markers, such as lipoproteins (high- and low-density lipoproteins), glucose, and valine, and lactic acid metabolic disturbance were recovered, to some extent, in HCC rats. Exogenous metabolites, diosgenin, apigenin-7-O-acetyl-ß-D-glucoside, calycosin-7-glucoside, calycosin, ganoderic-acid-A, formononetin, and methylnissolin, became detectable in the blood. FZYLD-containing serum substantially inhibited the proliferation of HepG2-cells. IC50 value was found to be 24.31%. Further, we confirmed that FZYLD could revert energy and lipid metabolism disorders and that its constituents could be bioactive components that induce apoptosis in cancer cells. Conclusion: The present study explained the mechanism of the effect of FZYLD on body empty, fatigue, and low immunity in patients with cancer, offering an efficient way for research of natural compounds in traditional Chinese medicine.

Ginsenoside Rb1 prevents osteoporosis via the AHR/PRELP/NF-κB signaling axis.

BACKGROUND: Accumulating clinical and experimental evidence shows multiple biological effects of ginsenoside Rb1 (GRb1) in the treatment of aging related diseases such as osteoporosis (OP). Recently, GRb1 has attracted extensive attention as an anti-osteoporosis agent. Here, we sought to identify the mechanism by which GRb1 improves OP. METHODS: A dexamethasone (DEX)-induced rat model of OP was constructed and the rats were treated with GRb1 to examine its role in OP. We screened the action targets of GRb1 online and validated by performing functional experiments. The correlation between aryl hydrocarbon receptor (AHR) and proline/arginine-rich end leucine-rich repeat protein (PRELP) was identified through luciferase and chromatin immunoprecipitation assays. In the isolated osteoblasts from DEX-induced OP rats, the expression of osteogenic differentiation-associated genes, and nuclear factor-kappa B (NF-κB) pathway-related genes, mineralization, and number of calcium nodules were assessed. RESULTS: GRb1 enhanced the differentiation of osteoblasts, the mechanism of which was related to upregulation of AHR. AHR could promote the transcription of PRELP by binding to the PRELP promoter region and consequently caused its upregulation. Meanwhile, PRELP inhibited the activation of the NF-κB pathway, which underlay the promoting impact of AHR in the osteogenic differentiation. Additionally, GRb1 could ameliorate OP in DEX-induced rats via the AHR/PRELP/NF-κB axis. CONCLUSIONS: Our findings demonstrate that GRb1 might function as an effective candidate to prevent the progression of OP via regulation of the AHR/PRELP/NF-κB axis, revealing a new molecular mechanism underpinning the impact of GRb1 in the progression of OP and offering a theoretical contribution to the treatment of OP.

Short-Term High-Fat Diet Fuels Colitis Progression in Mice Associated With Changes in Blood Metabolome and Intestinal Gene Expression.

Clinical cases and animal experiments show that high-fat (HF) diet is involved in inflammatory bowel disease (IBD), but the specific mechanism is not fully clear. A close association between long-term HF-induced obesity and IBD has been well-documented. However, there has been limited evaluation of the impact of short-term HF feeding on the risk of intestinal inflammation, particularly on the risk of disrupted metabolic homeostasis. In this study, we analyzed the metabolic profile and tested the vulnerability of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis after short-term HF feeding in mice. The results showed that compared with the control diet (CD), the fatty acid (FA), amino acid (AA), and bile acid (BA) metabolisms of mice in the HF group were significantly changed. HF-fed mice showed an increase in the content of saturated and unsaturated FAs and a decrease in the content of tryptophan (Trp). Furthermore, the disturbed spatial distribution of taurocholic acid (TCA) in the ileum and colon was identified in the HF group using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). After HF priming, mice on TNBS induction were subjected to more severe colonic ulceration and histological damage compared with their CD counterparts. In addition, TNBS enema induced higher gene expressions of mucosal pro-inflammatory cytokines under HF priming conditions. Overall, our results show that HF may promote colitis by disturbing lipid, AA, and BA metabolic homeostasis and inflammatory gene expressions.

Effects of Zhishi Daozhi Decoction on the intestinal flora of nonalcoholic fatty liver disease mice induced by a high-fat diet.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear. Methods: Mice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique. Results: ZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group. Conclusions: ZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.

A combination of garlic oil and cooked chilli oil could be effective and efficient for pigeon production.

This study was conducted to investigate whether the combination of garlic oil and cooked chilli oil is worth using for pigeon production in the context of a total ban on antibiotics in feed additives in China. Two hundred female white king pigeons aged 23 days were randomly divided into five groups with ten replicates (four birds each). In the 47 days trial, the control group was fed with a basal diet, treatment groups were given a basal diet supplemented with 20 mg/kg neomycin sulphate or 2 g/kg corresponding oil (garlic oil or cooked chilli oil or their mixture) respectively. The mixed oil showed obvious antibacterial activity against gram-positive bacterium and its minimal bactericidal concentration against St. aureus, Salmonella and Escherichia coli were all no more than 1.0 mg/ml. In the feeding experiment, pigeons feed with garlic oil with strong bacteriostatic activity had lower FCR and better protein metabolism, and chilli oil showed strong effects of promoting feed intake and weight gain on pigeons but increased serum glucose and lipid content. Compared with the control and the antibiotic group, the mixed oil got increased growth performance, less drip loss of meat, better protein metabolism promoting, and more complete intestinal structure of pigeon. In addition, the breast meat in the mixed oil group had higher total points in the sensory test. The mixed oil combined the strong bacteriostasis of garlic oil with the feeding promotion effect of cooked chilli oil, it improved the comprehensive performance of pigeons and had the feasibility to be popularized as a non-antibiotic strategy in pigeon production.

[Exploring and practicing over 80 years in traditional Chinese medicine: the academic career of professor XUE Chong-cheng].

This paper reviewes the clinical and scientific research history of professor XUE Chong-cheng and summarizes his academic thoughts and main achievements. Professor XUE Chong -cheng created the first personality and constitution inventory in China to lay the foundation for the discipline of TCM psychology; discovered meridian sensory conduction in phantom limbs and proposed the extension of the central model; invented a method for treating mental illness with a low-dose electroacupuncture convulsion therapy instrument; and interpreted the TCM medical model as a Time-Space-Social- Psychological-Biological medical model.

Acquisition of clofazimine resistance following bedaquiline treatment for multidrug-resistant tuberculosis.

OBJECTIVES: We described the prevalence of clofazimine (CFZ) resistance in a multidrug-resistant tuberculosis (MDR-TB) cohort in China. We also aimed to identify dynamic changes in CFZ susceptibility and its molecular mechanism after exposure to bedaquiline (BDQ) and/or CFZ. METHODS: The experimental settings were conducted based on our MDR-TB cohort receiving BDQ-containing regimens. Sequential isolates were obtained from patients. CFZ and BDQ susceptibility of isolates were determined using the minimum inhibitory concentration (MIC) method. The fragments of Rv0678 and pepQ were sequenced. RESULTS: A total of 277 patients infected with MDR-TB were included in our study. CFZ resistance was noted in 23 (23/277, 8.3%) isolates. The rate of acquired CFZ resistance (12/189, 6.3%) was significantly greater than that of primary resistance (11/88, 12.5%, P = 0.028). Out of 23 CFZ-resistant isolates, five (5/23) were BDQ-resistant, and the other 18 (18/23) were susceptible to BDQ. Of note, nine 9/23) out of 23 CFZ-resistant isolates had mutations within either target genes. Kaplan-Meier analysis demonstrated that the baseline CFZ resistance had no influence on time to culture conversion in our cohort (P = 0.828). Acquired CFZ resistance emerged in eight (8/94, 8.5%) patients during treatment for MDR-TB, including three patients receiving regimens without CFZ. CONCLUSIONS: Our results demonstrate the high rate of CFZ resistance among MDR-TB patients in China. Patients treated with BDQ-containing regimens achieve comparative culture conversion rate regardless of baseline CFZ susceptibility. The presence of acquired CFZ-resistance following BDQ treatment without known mutation indicates that other mechanisms conferring cross resistance to these two compounds may exist.

Reduced Susceptibility of Mycobacterium tuberculosis to Bedaquiline During Antituberculosis Treatment and Its Correlation With Clinical Outcomes in China.

BACKGROUND: We aimed to assess the proportion of multidrug-resistant tuberculosis (MDR-TB) cases with initial bedaquiline (BDQ) resistance, monitor the dynamics of BDQ susceptibility of Mycobacterium tuberculosis isolates during therapy, and correlate susceptibility with MDR-TB patient clinical outcomes in China. METHODS: A retrospective, cohort study of MDR-TB patients was conducted, with positive cultures collected from cases at 13 sites. Patients with nontuberculous mycobacterial infection during anti-TB therapy were excluded. BDQ minimal inhibitory concentrations (MICs) were determined using a 7H9 Middlebrook broth-based microdilution method. Mutations that conferred BDQ resistance were detected via Sanger sequencing. RESULTS: A total of 277 patients receiving BDQ treatment were studied, with BDQ resistance noted in isolates from 2.2% (6/277) of MDR-TB cases, sputum conversion observed in 5 cases, and culture conversion observed in 138 cases within 2 weeks. Another 15 and 30 isolates were excluded from final analysis due to failures in obtaining subcultures and serial isolates, respectively. Of 94 cases that yielded serial isolates, 11 exhibited reduced BDQ susceptibility, while 3 of 5 cases with acquired resistance failed to culture-convert. Sequence analysis revealed that 6 of 11 BDQ-resistant isolates harbored Rv0678 mutations; no mutations were detected in 3 other BDQ resistance-associated genes. No significant intergroup difference in culture conversion time was observed. CONCLUSIONS: MDR-TB patients in China exhibited a low initial BDQ resistance rate. MDR-TB cases with acquired BDQ resistance were at greater risk of treatment failure relative to initially BDQ-resistant cases. Rv0678 mutations accounted for BDQ resistance in this cohort.

Efficacy and Safety of Duhuo Jisheng Decoction for Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.

AIM: To evaluate the effects and medication safety of Duhuo Jisheng Decoction (DHJSD) alone or as a combination therapy with other interventions on the related clinical index in postmenopausal osteoporosis condition. METHODS: Search in CNKI, WanFang, CBM, VIP, PubMed, EMBASE, and Cochrane Library databases and randomized controlled trials where at least one group received any form of DHJSD for postmenopausal osteoporosis condition. Risk of bias was based on the Cochrane handbook, the quality of evidence was assessed by the GRADEpro online, and analyses were performed by RevMan 5.3 software. RESULTS: Eight studies were enrolled with 650 participants. DHJSD alone or with other interventions had a significant effect on BMD of the lumbar spine (MD = 0.46, 95%CI (0.24, 0.68), P < 0.0001), E2 (SMD = 0.49, 95%CI (0.30, 0.68), P < 0.0001), and clinical effectiveness (OR = 5.07, 95%CI (3.07, 8.35), P < 0.0001). However, no effect at BGP (MD = -0.84, 95%CI (-1.69, 0.00), P=0.05) was seen. CONCLUSION: The pooled estimate suggested that DHJSD combined with conventional medical therapies has a certain clinical curative effect on postmenopausal osteoporosis. However, considering the unsatisfactory quality of included trials, more high-quality trials are needed to elucidate this issue.

Effects of cardiopulmonary bypass with low-priming volume on clinical outcomes in children undergoing congenital heart disease surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) with high-priming volume can significantly activate the inflammatory response and increse the usage of packed red blood cells (PRBCs). As risks and complications related to transfusions are increasing, many cardiac centers are focusing on reducing the priming volume of CPB. In our center, efforts have also been made to reduce the priming volume, and the effects of CPB with low-priming volume on clinical outcomes in children undergoing congenital heart disease (CHD) surgery were investigated in this study to provide referential experiences for pediatric CPB. METHODS: The clinical case data of 158 children undergoing CHD surgery with CPB were collected. The children were divided into the low-priming-volume group (group A, n = 79) and the traditional group (group B, n = 79) according to the priming volume. The amount of PRBCs transfused, the postoperative hematological test results and the clinical outcomes of the two groups were compared by the independent sample t-test or the chi-square test. RESULTS: The amount of PRBCs transfused during CPB and during the whole operation were significantly lower in group A than in group B (p < 0.01), but the hemoglobin (Hb) concentration was higher in group A on the first day after surgery (p < 0.01) and before hospital discharge. However, the latter showed no statistical significant difference. The lowest postoperative platelet count was higher in group A than in group B (p < 0.05). There was no statistical difference in the postoperative inflammatory markers and the main clinical outcomes between the two groups. CONCLUSIONS: The usage of PRBCs in CPB with low-priming volume decreased significantly, but the postoperative Hb concentration and platelet count could still be maintained at a high level, improving the use efficiency of PRBCs. CPB with low-priming volume did not affect the postoperative recovery of patients, so it is worthy of continuous promotion and optimization.

Mechanism differences between typical yin and typical yang personality individuals assessed by Five-Pattern Personality Inventory (FPPI): Evidence from resting-state brain functional networks.

BACKGROUND: Most studies assessing brain-personality mechanisms have used Western personality questionnaires. However, Western personality questionnaires may not objectively reflect the personality characteristics of individuals in Eastern cultures such as China. Hence, we adopted the functional magnetic resonance imaging (fMRI) and the Chinese localized scale, FPPI, to explore the brain mechanisms differences of typical yin and typical yang personalities of individuals in China. METHODS: 30 typical yin personality participants (TYI) and 34 typical yang personality participants (TYA) were enrolled according to the FPPI. The group differences of the functional brain networks among 90 specific brain regions were mapped using fMRI data and then analyzed by the conventional network metrics (CNM) and frequency subgraph mining (FSM). RESULTS: The CNM and FSM differences between two typical personality groups were traced to the frontal, temporal, and parietal cortices. The yin group, reflecting the rich emotions and feelings of individuals, showed higher betweenness centrality (BCi) and nodal efficiency (Ei) values in putamen and middle frontal gyrus. The yang group, reflecting active behaviors and tendency to adapting to the changing surroundings, showed higher BCi and Ei values in precuneus, posterior cingulate gyrus, and inferior parietal lobule, brain areas in the default mode network (DMN). CONCLUSION: These results supplied evidence for the neurobiological differences between typical yin and typical yang personality participants based on Chinese culture. These results also provide a new perspective to help researchers understand brain mechanism differences between yin and yang personality groups in the Chinese culture.

The efficacy of Chinese herbal medicines on acute coronary syndrome with renal insufficiency after percutaneous coronary intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Chuanxiong capsule consists of Angelica sinensis radix and Chuanxiong rhizome, which are used in the traditional Chinese medicine for the treatment of coronary artery disease, and Xinyue capsule is composed of panax quinquefolius saponin extracted from leaves and stems of Panax quinquefolium L, which has the functions of anti-myocardial ischemia, improving myocardial energy metabolism and inhibiting apoptosis of cardiomyocytes. OBJECTIVE: To observe the role of Chinese herbal medicines in the cardiovascular outcome among patients with acute coronary syndrome (ACS) and renal insufficiency after percutaneous coronary intervention (PCI). METHODS: The subjects came from the 5C trial (chictr.org number: chictr-trc-07000021), post-PCI patients suffered from ACS with mild-to-moderate renal insufficiency (30 mL•min-1•1.73 m-2 < estimated glomerular filtration rate≤89 mL•min-1•1.73 m-2) included. The study population consisted of 215 subjects in the control group who were treated with western medicine standard therapy, and 211 subjects in the treatment group who were treated with Chinese herbal medicines (Fufang Chuanxiong Capsule and Xinyue Capsule) for 6 months on the basis of western medicine standard therapy. All were followed for 1 year. The primary endpoint included the composite of cardiac death, nonfatal recurrent myocardial infarction, and ischemia-driven revascularization. Secondary endpoint included the composite of stroke, congestive heart failure, and readmission for ACS. The serum creatinine and estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: After 1 year follow-up of two groups, there were 16 cases of primary endpoint in the control group and 6 cases of primary endpoint in the treatment group [absolute risk reduction (ARR): 0.046, 95%CI: 0.004-0.088; relative risk (RR): 0.38, 95%CI: 0.15-0.96, P = 0.040]. There were 15 cases of secondary endpoint in the control group and 5 cases of secondary endpoint in the treatment (ARR: 0.041, 95%CI: 0.006-0.086; RR: 0.34, 95%CI: 0.13-0.92, P = 0.033). The eGFR in the treatment group was significantly higher than that in the control group (75.19 ±â€¯16.74 mL min-1·1.73 m-2 VS 72.03 ±â€¯14.96 mL min-1·1.73 m-2, P < 0.05). The eGFR in the treatment group was significantly higher after the intervention with Chinese herbal medicines than that before intervention (72.27 ±â€¯11.83 mL min-1·1.73 m-2 VS 75.19 ±â€¯16.74 mL min-1·1.73 m-2, P < 0.05). CONCLUSION: Chinese herbal medicines plus western medicine standard therapy improved clinical outcomes in patients with ACS and mild-to-moderate renal insufficiency. Additionally, this study also demonstrated Chinese herbal medicines were useful in deferring decline of renal function.

Systems Pharmacology Dissection of Multiscale Mechanisms of Action for Herbal Medicines in Treating Rheumatoid Arthritis.

As a chronic inflammatory and angiogenic disease with increased morbidity and mortality, rheumatoid arthritis (RA) is characterized by the proliferation of synovial tissue and the accumulation of excessive mononuclear infiltration, which always results in the joint deformity, disability, and eventually the destruction of the bone and cartilage. Traditional Chinese Medicine (TCM), with rich history of proper effectiveness in treating the inflammatory joint disease containing RA, has long combated such illness from, actually, an integrative and holistic point of view. However, its "multi-components" and "multi-targets" features make it very difficult to decipher the molecular mechanisms of RA from a systematic perspective if employing only routine methods. Presently, an innovative systems-pharmacology approach was introduced, which combined the ADME screening model, drug targeting, and network pharmacology, to explore the action mechanisms of botanic herbs for the treatment of RA. As a result, we uncovered 117 active compounds and 85 key molecular targets from seven RA-related herbs, which are mainly implicated in four signaling pathways, that is, vascular endothelial growth factor, PI3K-Akt, Toll-like receptor, and T-cell-receptor pathways. Additionally, the network relationships among the active components, target proteins, and pathways were further built to uncover the pharmacological characters of these herbs. Besides, molecular dynamics (MD) simulations and molecular mechanics-Poisson-Boltzmann surface area calculations were carried out to explore the binding interactions between the compounds and their receptors as well as to investigate the binding affinity of the ligand to their protein targets. In vitro experiments by ligand binding assays validate the reliability of the drug-target interactions as well as the MD results. The high binding affinities and good inhibitions of the active compounds indicate that the potential therapeutic effects of these herbal medicines for treating RA are exerted probably through the modulation of these relevant proteins, which further validates the rationality and reliability of the drug-target interactions as well as our the network-based analytical methods. This work may be of help for not only understanding the action mechanisms of TCM and for discovering new drugs from plants for the treatment of RA, but also providing a novel potential method for modern medicine in treating complex diseases.

A New Strategy for Deleting Animal drugs from Traditional Chinese Medicines based on Modified Yimusake Formula.

Traditional Chinese medicine (TCM), such as Uyghur Medicine (UM) has been used in clinical treatment for many years. TCM is featured as multiple targets and complex mechanisms of action, which is normally a combination of medicinal herbs and sometimes even contains certain rare animal medicinal ingredients. A question arises as to whether these animal materials can be removed replaced from TCM applications due to their valuable rare resources or animal ethics. Here, we select a classical UM Yimusake formula, which contains 3 animal drugs and other 8 herbs, and has got wealthy experience and remarkable achievements in treating erectile dysfunction (ED) in China. The active components, drug targets and therapeutic mechanisms have been comprehensively analyzed by systems-pharmacology methods. Additionally, to validate the inhibitory effects of all candidate compounds on their related targets, in vitro experiments, computational analysis and molecular dynamics simulations were performed. The results show that the modified, original and three animal materials display very similar mechanisms for an effective treatment of ED, indicating that it is quite possible to remove these three animal drugs from the original formula while still keep its efficiency. This work provides a new attempt for deleting animal materials from TCM, which should be important for optimization of traditional medicines.

A randomized, controlled comparison of different intensive lipid-lowering therapies in Chinese patients with non-ST-elevation acute coronary syndrome (NSTE-ACS): Ezetimibe and rosuvastatin versus high-dose rosuvastatin.

BACKGROUND: Statin combined with ezetimibe demonstrates significant benefit in lowering low density lipid cholesterol (LDL-C) and cardiovascular events abroad, but whether intermediate intensity statins combined with ezetimibe is superior to high-intensity statin monotherapy in Chinese people is unknown. METHODS: A total of 125 patients were randomly assigned to a intermediate intensity rosuvastatin group (rosuvastatin 10mg/d, n=42), high-dose rosuvastatin group (rosuvastatin 20mg/d, n=41) or combination therapy group (ezetimibe 10mg/d and rosuvastatin 10mg/d, n=42) with a 12-week follow-up. The primary end point was the proportion of patients who achieved the 2011 ESC/EAS LDL-C goal <70mg/dL (1.8mmol/L) at week 12. Secondary end points included changes from baseline in lipids, the occurrence of all cardiovascular events, high-sensitivity C-reactive protein and safety markers. RESULTS: The combination therapy group in the primary end point was significantly higher than rosuvastatin (20mg) and rosuvastatin (10mg) at week 12 (81.0% vs 68.3% vs 33.3%, P<0.001). And the similar change was observed in reducing LDL-C levels at week 12 (67.28% vs 52.80% vs 43.89%, P<0.001). The incidence of drug-related adverse events was much higher in the rosuvastatin 20mg group than the rosuvastatin 10mg group and the combination therapy group (17.0% vs 2.4% vs 4.8%, P<0.05). CONCLUSIONS: The combination of rosuvastatin 10mg/ezetimibe 10mg was an effectively alternative therapy superior to rosuvastatin 20mg or 10mg with a greater effect on lowering LDL-C and a lower incidence of drug-related adverse events in Chinese patients.