MiR-22-3p facilitates bone marrow mesenchymal stem cell osteogenesis and fracture healing through the SOSTDC1-PI3K/AKT pathway.

Bone fractures are the most common form of musculoskeletal trauma worldwide. Numerous microRNAs (miRNAs) have been suggested to be participants in regulating bone-related diseases. Recent studies revealed the regulatory role of miR-22-3p in osteogenic differentiation, but its role in fracture healing has not been investigated previously. Here, a rat femoral fracture model was established, Bone marrow mesenchymal stem cells (BMSCs) were isolated to detect the specific function and underlying mechanisms of miR-22-3p. MiR-22-3p and sclerostin domain-containing 1 (SOSTDC1) expression was determined by RT-qPCR and immunohistochemistry staining. The levels of proteins associated with osteogenic differentiation were assessed by western blotting. Flow cytometry was conducted to identify the isolated rat BMSCs. Alizarin red staining, alkaline phosphatase staining and Oil Red O staining were used to evaluate the osteogenic and adipogenic differentiation of rat BMSCs. The interaction between miR-22-3p and SOSTDC1 was verified using a luciferase reporter assay. Haematoxylin and Eosin (H&E) staining of the bone tissues was performed to analyse the effect of miR-22-3p on histopathological changes in vivo. MiR-22-3p was downregulated in the callus tissues of rat femoral fracture, while the expression of SOSTDC1 was upregulated. The isolated rat BMSCs had the capacity for both osteogenic and adipogenic differentiation. The differentiation capacity of BMSCs into osteoblasts was increased by miR-22-3p overexpression. MiR-22-3p activated the PI3K/AKT pathway by targeting SOSTDC1. SOSTDC1 overexpression and PI3K/AKT signalling inhibitor LY294002 abolished the enhancing effect of miR-22-3p overexpression on the osteogenesis of BMSCs. Thus MiR-22-3p facilitated the femoral fracture healing in rats. MiR-22-3p overexpression promoted fracture healing via the activation of PI3K/AKT pathway by targeting SOSTDC1.

Study on the enhanced efficacy mechanism of vinegar-processed Cyperus rotundus in the treatment of primary dysmenorrhea.

The enhanced efficacy of vinegar-processed Cyperus rotundus (VCR) in treating primary dysmenorrhea (PD) has been observed. However, the active components and potential mechanisms of synergy are still unclear. The objective of this study was to develop a method that combines bionic technology, plant metabolomics and network pharmacology to discover the active components and potential mechanisms underlying the enhanced therapeutic effects of VCR for PD. Vinegar processing alters the flavor of C. rotundus, leading to changes in its properties. The acidic nature of vinegar enhances the selectivity of the medicine toward the liver, thereby improving its ability to soothe the liver, regulate qi and provide pain relief. Through gas chromatography-mass spectrometry and multivariate statistical analysis, 30 key differential components between raw C. rotundus and VCR have been screened and identified. These differential components primarily exert their therapeutic effects in treating PD by modulating targets such as interleukin-6, TNF, TP53 and PTGS2, as well as pathways including the estrogen signaling pathway, ovarian steroidogenesis, the TNF signaling pathway and the HIF-1 signaling pathway. The findings of this study serve as a reference for the application of VCR in compound formulas and clinic practiceal. Furthermore, the methodology employed in this study provides research insights for the processing of other Chinese medicines.

Hesperidin Anti-Osteoporosis by Regulating Estrogen Signaling Pathways.

Osteoporosis (OP) is distinguished by a reduction in bone mass and degradation of bone micro-structure, frequently resulting in fractures. As the geriatric demographic expands, the incidence of affected individuals progressively rises, thereby exerting a significant impact on the quality of life experienced by individuals. The flavonoid compound hesperidin has been subject to investigation regarding its effects on skeletal health, albeit the precise mechanisms through which it operates remain ambiguous. This study utilized network pharmacology to predict the core targets and signaling pathways implicated in the anti-OP properties of hesperidin. Molecular docking and molecular dynamics simulations were employed to confirm the stability of the interaction between hesperidin and the core targets. The effects of hesperidin on osteoblastic cells MC3T3-E1 were assessed using MTT, ELISA, alkaline phosphatase assay, and RT-qPCR techniques. Furthermore, in vivo experiments were conducted to determine the potential protective effects of hesperidin on zebrafish bone formation and oxidative stress response. The results demonstrate that network pharmacology has identified 10 key target points, significantly enriched in the estrogen signaling pathway. Hesperidin exhibits notable promotion of MC3T3-E1 cell proliferation and significantly enhances ALP activity. ELISA measurements indicate an elevation in NO levels and a reduction in IL-6 and TNF-α. Moreover, RT-qPCR analysis consistently reveals that hesperidin significantly modulates the mRNA levels of ESR1, SRC, AKT1, and NOS3 in MC3T3-E1 cells. Hesperidin promotes osteogenesis and reduces oxidative stress in zebrafish. Additionally, we validate the stable and tight binding of hesperidin with ESR1, SRC, AKT1, and NOS3 through molecular dynamics simulations. In conclusion, our comprehensive analysis provides evidence that hesperidin may exert its effects on alleviating OP through the activation of the estrogen signaling pathway via ESR1. This activation leads to the upregulation of SRC, AKT, and eNOS, resulting in an increase in NO levels. Furthermore, hesperidin promotes osteoblast-mediated bone formation and inhibits pro-inflammatory cytokines, thereby alleviating oxidative stress associated with OP.

[Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome].

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.

Quality evaluation of the classical prescription, Danggui Jianzhong decoction, using ultra-high-performance liquid chromatography fingerprint, chemical pattern recognition, and network pharmacology.

Danggui Jianzhong decoction is a classical prescription that has been widely used for thousands of years. However, the quality of this formula is difficult to control owing to its complex chemical component system. In this study, a simple and efficient method comprising ultra-high-performance liquid chromatography fingerprint, chemical pattern recognition, and network pharmacology was established to evaluate the quality of this decoction. A total of 20 common peaks were obtained by fingerprint analysis and 19 chemicals were identified. The fingerprint similarity of 15 batch samples ranged from 0.963 to 0.991. Chemical pattern recognition analysis could clearly classify 15 batches of Danggui Jianzhong decoction into three groups. Further, seven chemical markers were screened out. A herbs-active components-targets-disease network was constructed and enrichment analyses were performed, which indicated that these 19 chemical components are the medicinal substances of Danggui Jianzhong decoction. Further, the mechanism employed by this formula to treat primary dysmenorrhea may be related to the regulation of inflammatory response. In conclusion, this combination approach enables accurate evaluation and prediction of the quality of Danggui Jianzhong decoction, and lays the foundation for studies on the material basis and exploration of the mechanism of Danggui Jianzhong decoction in the treatment of primary dysmenorrhea.

Effects of sevoflurane exposure on apoptosis and cell cycle of peripheral blood lymphocytes, and immunologic function.

BACKGROUND: Waste anesthetic gases (WAGs) leaked from new-type halogenated inhalational anesthetics such as sevoflurane have been were reported to pose a risk for the health of operating room personnel. The effects of WAGs on peripheral blood lymphocytes, however, remain yet controversial. The present study was undertaken to examine the effects of occupational sevoflurane exposure on the peripheral blood lymphocytes of medical personnel who work in the operating room. METHODS: A cohort of 56 medical residents were divided into exposed group (n = 28) and control group (non-exposed group) (n = 28). Gas chromatography was used to measure the concentration of sevoflurane in the medical resident's breathing zone during surgeries under inhalation anesthesia in the exposure group. The gas collection lasted an hour. Peripheral blood lymphocytes were isolated from venous blood, and then apoptosis and cell cycle were analyzed by flow cytometry. EDTA-anticoagulated whole blood was harvested to analyze the lymphocyte subsets by flow cytometry. Immunoglobulins (IgA, IgM, IgG) were quantified by immunoturbidimetry. RESULTS: The average concentration of sevoflurane in the exposed group was 1.03 ppm with a range from 0.03 ppm to 2.24 ppm. No significant effects were found on the apoptosis rates or cell cycles of peripheral blood lymphocytes in the exposed group relative to the control group (P > 0.05). Similarly, there were no significant differences in the lymphocyte subsets or the levels of immunoglobulins (IgA, IgM, IgG) between the two groups (P > 0.05). CONCLUSIONS: Occupational exposure to low-level sevoflurane has no significant effect on the peripheral blood lymphocytes of operating room staff, but this conclusion needs to be confirmed by multicenter and long-term follow-up studies with large samples. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ChiCTR2000040772 , December 9, 2020 (Retrospective registration).

KRAS-retroviral fusion transcripts and gene amplification in arsenic-transformed, human prostate CAsE-PE cancer cells.

CAsE-PE cells are an arsenic-transformed, human prostate epithelial line containing oncogenic mutations in KRAS compared to immortalized, normal KRAS parent cells, RWPE-1. We previously reported increased copy number of mutated KRAS in CAsE-PE cells, suggesting gene amplification. Here, KRAS flanking genomic and transcriptomic regions were sequenced in CAsE-PE cells for insight into KRAS amplification. Comparison of DNA-Seq and RNA-Seq showed increased reads from background aligning to all KRAS exons in CAsE-PE cells, while a uniform DNA-Seq read distribution occurred in RWPE-1 cells with normal transcript expression. We searched for KRAS fusions in DNA and RNA sequencing data finding a portion of reads aligning to KRAS and viral sequence. After generation of cDNA from total RNA, short and long KRAS probes were generated to hybridize cDNA and KRAS enriched fragments were PacBio sequenced. More KRAS reads were captured from CAsE-PE cDNA versus RWPE-1 by each probe set. Only CAsE-PE cDNA showed KRAS viral fusion transcripts, primarily mapping to LTR and endogenous retrovirus sequences on either 5'- or 3'-ends of KRAS. Most KRAS viral fusion transcripts contained 4 to 6 exons but some PacBio sequences were in unusual orientations, suggesting viral insertions within the gene body. Additionally, conditioned media was extracted for potential retroviral particles. RNA-Seq of culture media isolates identified KRAS retroviral fusion transcripts in CAsE-PE media only. Truncated KRAS transcripts suggested multiple retroviral integration sites occurred within the KRAS gene producing KRAS retroviral fusions of various lengths. Findings suggest activation of endogenous retroviruses in arsenic carcinogenesis should be explored.

Efficient 3D silicon mode (de)multiplexer based on a sidewall-aligned vertical coupler.

An efficient three-dimensional (3D) quasi-TE0 and quasi-TE1 mode (de)multiplexer [(De)MUX] is proposed and optimized based on a dual-waveguide 3D-coupler, in which the sidewalls of a bottom silicon waveguide and an upper poly-silicon waveguide are aligned vertically. The full-vectorial finite element method and 3D full-vectorial finite difference time domain method are utilized to study the performances of the proposed 3D mode (De)MUX. The results indicate that the proposed mode (De)MUX can achieve a compact coupling length of 6.88 µm, a mode crosstalk of -30.04dB, an insertion loss of 0.02 dB, and an ultra-broad 1 dB bandwidth of 300 nm. The proposed 3D mode (De)MUX based on a sidewall-aligned vertical coupler has the potential to extend the functionality and to increase the integration of the mode division multiplexing (MDM) systems.

Screening and Identification of the Main Metabolites of Schisantherin a In Vivo and In Vitro by Using UHPLC-Q-TOF-MS/MS.

Schisantherin A is an active ingredient originating from Schisandra chinensis (Turcz.) which has hepatoprotective and anti-oxidation activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on male Sprague Dawley rats of Schisantherin A were tested, respectively. The metabolites of Schisantherin A were identified using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the method, 60 metabolites were successfully identified and structurally characterized including 48 phase-I and 12 phase-II metabolites. Among the metabolites, 45 metabolites were reported for the first time. Moreover, 56 and eight metabolites were detected in urine and bile and 19 metabolites were identified in rats' plasma. It demonstrated that hepatic and extra-hepatic metabolic pathways were both involved in Schisantherin A biotransformation in rats. Five in vitro metabolites were structurally characterized for the first time. The results indicated that the metabolic pathways mainly include oxidation, reduction, methylation, and conjugation with glucuronide, taurine, glucose, and glutathione groups. This study provides a practical strategy for rapidly screening and identifying metabolites, and the results provide basic data for future pharmacological and toxicology studies of Schisantherin A and other lignin ingredients.

Catheter-Based Renal Denervation Attenuates Kidney Interstitial Fibrosis in a Canine Model of High-Fat Diet-Induced Hypertension.

BACKGROUND/AIMS: Catheter-based renal denervation (RDN) has emerged as an innovative interventional approach for reducing blood pressure (BP), suppressing ventricular substrate remodeling, and attenuating heart failure, which suggests that it might reduce kidney fibrosis in a canine model of high-fat diet-induced hypertension. This study thus sought to assess whether RDN could reduce kidney fibrosis and halt the progression of renal impairment in a canine model of high-fat diet-induced hypertension. METHODS: Thirty-two beagles were randomized into either the normal control group (normal diet, n = 10) or the hypertension group (high-fat diet, n = 22). After successful establishment of the model, the hypertension model group was randomized to either the RDN group (n = 9) or the sham-surgery group (n = 8). Renal artery angiography, BP, heart rate (HR), and blood and urine biochemistry results were assessed at 1, 3, and 6 months after surgery. Canines were sacrificed at 6 months after surgery. The extent of kidney interstitial fibrosis, transforming growth factor-beta 1, alpha-smooth muscle actin, connective tissue growth factor, and E-cadherin protein were measured. RESULTS: The group fed a high-fat diet had significantly (p ˂ 0.05) increased body weight, BP, and HR and higher levels of urine albumin, serum noradrenaline (NE), and angiotensin II (AngII) than the control group. The sham-surgery group and RDN group also had higher levels than the control group (p ˂ 0.05). Compared with the sham-surgery group, the RDN group had lower BP, urine albumin, serum NE, and AngII and less fibrotic tissue (all p ˂ 0.05). CONCLUSION: RDN reduced BP, slowed progression of albuminuria, and suppressed renal remodeling in a canine model of high-fat diet-induced hypertension.

Comparison of long-term outcomes of young patients after a coronary event associated with familial hypercholesterolemia.

OBJECTIVE: Familial hypercholesterolemia (FH) is an important cause of premature coronary artery disease (CAD). Prognosis data are lacking in patients with FH and coronary artery disease particularly in the era of widespread statin use. We compared long-term prognosis between patients with and without FH after a coronary event. METHODS: In this retrospective study, 865 patients younger than 40 years of age with CAD were enrolled. FH was diagnosed based on the Dutch Lipid Clinic Network algorithm. Baseline characteristics, coronary angiographic findings and prognosis during median follow-up of 5 (3-8) years were compared between patients with or without FH. RESULTS: Definite or probable FH was detected in 37 patients (4.3%) and possible FH in 259 patients (29.9%). FH was associated with significantly higher prevalence of multi-vessel lesions (p < 0.001) and higher Gensini score (p = 0.008). In the subset of 706 patients for whom follow-up data were available, 127 (18.0%) suffered major adverse cardiovascular and cerebrovascular events (MACCE). FH was associated with increased risk of MACCE, independently of age, sex, smoking, body mass index, hypertension or diabetes mellitus (HR = 2.30, 95%CI = 1.09 to 4.84, p = 0.028). CONCLUSIONS: FH is an independent risk factor for MACCE in young patients after a coronary event during long-term follow-up. It is necessary to optimize lipid treatment of patients with FH after a coronary event.

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer.

BACKGROUND/AIMS: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer. METHODS: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy. RESULTS: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro. CONCLUSIONS: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

Preliminary Study of the Role F-Box Protein 32 (FBXO32) in Colorectal Neoplasms Through the Transforming Growth Factor beta (TGF-ß)/Smad4 Signalling Pathway.

BACKGROUND F-box protein 32 (FBXO32) (also known as atrogin-1), a member of the F-box protein family, was recently shown to be a transforming growth factor beta (TGF-ß)/Smad4 target gene involved in regulating cell survival. It can be transcriptionally silenced by epigenetic mechanisms in some cancers, but its role in colorectal carcinoma (CRC) is unclear. We investigated the role of FBXO32 in CRC and determined its prognostic significance. MATERIAL AND METHODS We used real-time quantitative PCR, Western blot, and immunohistochemistry to elucidate the role of FBXO32 in clinical specimens and primary CRC cell lines. Differences in patient survival were determined by the Kaplan-Meier method and log-rank test. RESULTS We found that the FBXO32 and SMAD4 levels were higher in normal tissues than in CRC tissues, but PAI-1 and VEGF levels showed the opposite pattern. The expressions of FBXO32 and SMAD4 were related to clinicopathological parameters in CRC. Kaplan-Meier analyses showed that the 5-year overall survival of the low-FBXO32 expression group was significantly shorter than that of the high-FBXO32 expression group (p=0.010). CONCLUSIONS The fbxo32 gene is a novel tumor suppressor that inhibits CRC progression by inducing differentiation. Elevated expression of FBXO32 predicts longer survival in CRC patients.

Molecular identification of Neofabraea species associated with bull's-eye rot on apple using rolling-circle amplification of partial EF-1α sequence.

A rolling-circle amplification (RCA) method with padlock probes targeted on EF-1α regions was developed for rapid detection of apple bull's-eye rot pathogens, including Neofabraea malicorticis, N. perennans, N. kienholzii, and N. vagabunda (synonym: N. alba). Four padlock probes (PLP-Nm, PLP-Np, PLP-Nk, and PLP-Nv) were designed and tested against 28 samples, including 22 BER pathogen cultures, 4 closely related species, and 2 unrelated species that may cause serious apple decays. The assay successfully identified all the bull's-eye rot pathogenic fungi at the level of species, while no cross-reaction was observed in all target species and no false-positive reaction was observed with all strains used for reference. This study showed that the use of padlock probes and the combination of probe signal amplification by RCA provided an effective and sensitive method for the rapid identification of Neofabraea spp. The method could therefore be a useful tool for monitoring bull's-eye rot pathogens in port quarantine and orchard epidemiological studies.

Screening and identification of multiple constituents and their metabolites of Zhi-zi-chi decoction in rat urine and bile by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Zhi-zi-chi decoction (ZZCD) is a classical formula widely used in Chinese clinical application. In the present study, a novel and efficient strategy has been developed for screening and identification of multiple constituents and their metabolites of ZZCD using ultra-high-performance liquid chromatography combined with triple time-of-flight mass spectrometry. The novel approach of an online data acquisition method dependent on multiple mass defect filter and dynamic background subtraction is combined with multiple data processing techniques. First, a total of 109 potential bioactive compounds were detected in ZZCD. Based on the same instrumental conditions, 100 compounds were found in rat biofluids after oral administration of ZZCD, including 61 original compounds of ZZCD as well as 39 metabolites. Conjugations with sulfate, glucuronate and amino acids were found as the predominant metabolic reaction of ZZCD. As more xenobiotics were detected in urine than those in bile were, it demonstrated that multiple components of ZZCD have undergone comprehensive renal excretion. This study reported the urinary and biliary excretion in rats after oral administration of ZZCD for the first time. The present study expands our knowledge about the constituents and metabolism of ZZCD, which could be very useful for further pharmacological and clinical studies of ZZCD.

Identify Unsuitable Patients with Left Main Coronary Artery Disease in Intermediate SYNTAX Scores Treated by Percutaneous Coronary Intervention.

BACKGROUND: With the follow-up extending to 5 years, the outcomes of SYNTAX (Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) trial were comparable between coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in left-main (LM) patients with intermediate SYNTAX scores of 23-32. A subdivision depending on SYNTAX score will help to identify unsuitable LM patients with intermediate SYNTAX scores to receive PCI treatment. METHODS: Between January 2011 and June 2013, 104 patients with LM Coronary Artery Disease (CAD) undergoing PCI were selected retrospectively. We compared clinical outcomes in patients with SYNTAX score <27 and ≥27. The follow-up time was 25.23 ± 7.92 months. Kaplan-Meier survival analyses and Cox proportional hazards models were used to compare various outcomes between two groups. RESULTS: Higher rates of repeated revascularization (18.2% versus 4.2%, P = .027) and major adverse cerebro-cardiovascular events (MACCE) (24.2% versus 7.0%, P = .014) were shown in patients with SYNTAX score ≥ 27. After multivariate adjustment, a significant higher risk of repeated revascularization (hazard ratio: 6.25, 95% confidence interval: 1.48 to 26.37, P = .013) and MACCE (hazard ratio: 4.49, 95% confidence interval: 1.41 to 14.35, P = .011) were also found in patients with SYNTAX score ≥ 27. CONCLUSIONS: Based on the higher rate of repeated revascularization and MACCE, patients with LM CAD and intermediate SYNTAX scores will need a subdivision to identity the one not benefit from PCI. CABG is still the standard treatment method for patients of LM CAD with a SYNTAX score of ≥ 27.

[Effect of Acupoint Application Therapy of Summer Treatment for Winter Diseases on Nerve-Endocrine-Immune Network System in Patient with Non-Acute Attack Asthma].

Objective To observe the effect of acupoint application therapy in summer to treat winter diseases (abbreviated as AATSTWD) on nerve-endocrine-immune network system in patients with non-acute attack asthma, and to study possible mechanisms. Methods Fifty healthy volunteers were re- cruited as the normal control group and 50 patients with non-acute attack asthma were recruited as the asthma group. Patients in the normal control group received no intervention. Those in the control group were treated with acupoint application therapy on hot days (applied on the first day of three dog days, 3 times in total). Blood samples were tested before treatment and after 3 times of application. The contents of serum immunoglobulin E (IgE) , interleukin-4 (IL-4) , plasma substance P (SP) , and vasoactive intes- tinal peptide (VIP) were detected using radioimmunoassay. Contents of immunoglobulin A and G (IgA, IgG) were tested by immunoturbidimetry. Content of interferon-y (INF-y) were tested by enzyme linked immunosorbent assay. Results Compared with the normal control group, serum contents of IgA, igG, IFN-y, and plasma VIP decreased, contents of IgE, IL-4, and SP significantly increased in the asthma group before treatment (P <0. 05). Compared with before treatment in the same group, serum contents of IgA, IgG, VIP, and IFN-y increased, and contents of IgE, IL-4, and SP decreased in the asthma group after treatment (P <0. 05). Conclusion Acupoint application therapy in summer to treat winter diseases method could prevent and treat bronchial asthma possibly through improving immune function, control- ling the release of cytokines , and regulating neurotransmitters.

Lattice-Matched Epitaxial Growth of Organic Heterostructures for Integrated Optoelectronic Application.

Development of nanowire photonics requires integration of different nanowire components into highly ordered functional heterostructures. Herein, we report a sequential self-assembly of binary molecular components into branched nanowire heterostructures (BNHs) via lattice-matched epitaxial growth, in which the microribbon backbone of 2,5-Bis(5-tert-butyl-2-benzoxazolyl)thiophene (BBOT) functions as blue-emitting microlaser source to pump the nanowire branches of BODIPY. By constructing Au electrodes on both branch sides and measuring the photocurrent in them, we successfully realize the integration of an organic laser and a power meter in a single device. This work provides a new insight into the integration of 1D organic nanostructures into BNHs for realizing organic multifunctional photonic devices.

Studies on metabolism of total glucosides of paeony from Paeoniae Radix Alba in rats by UPLC-Q-TOF-MS/MS.

Total glucosides of paeony are the active constituents of Paeoniae Radix Alba. In this study, a novel strategy was proposed to find more metabolites and the differences between paeoniflorin, albiflorin and total glucosides of paeony (TGP). This strategy was characterized as follows: firstly, the animals were divided into three groups (paeoniflorin, albiflorin and TGP) to identify the source of TGP metabolites from paeoniflorin or albiflorin; secondly, a generic information-dependent acquisition scan for the low-level metabolites was triggered by the multiple mass defect filter and dynamic background subtraction; thirdly, the metabolites were identified with a combination of data-processing methods including mass defect filtering, neutral loss filtering and product ion filtering; finally, a comparative study was used in the metabolism of paeoniflorin, albiflorin and TGP. Based on the strategy, 18 metabolites of TGP, 10 metabolites of paeoniflorin and 13 metabolites of albiflorin were identified respectively. The results indicated that the hydrolysis, conjugation reaction and oxidization were the major metabolic pathways, and the metabolic sites were the glycosidic linkage, the ester bond and the benzene ring. This study is first to explore the metabolism of TGP, and these findings enhance our understanding of the metabolism and the interactions of paeoniflrin and albiflorin in TGP.

[Regulation of hydrogen sulfide on transporter protein Bsep and Mdr2 in acute liver failure].

OBJECTIVE: To observe the effect of hydrogen sulfide on Bsep and Mdr2 in acute liver failure induced by thioacetamide. METHODS: Twenty-four male SD rats were randomly divided into thioacetamide (TAA) induced model group (n=6), control group (n=6), TAA+sodium hydrosulfide group (n=6), and TAA+ propargylglycine group (n=6). TAA was given to enterocoelia at the dose of 600 mg/kg for the model group, sodium hydrosulfide group and propargylglycine group rats.Sodium hydrosulfide with the dose of 0.15 mmol/kg and propargylglycine of 30 mg/kg was injected into enterocoelia one hour before the TAA used. All rats were sacrificed and serum specimen was collected to test hydrogen sulfide and hepatic function. The method of Western blot and Immunohistochemistry were used to measure the expression of Bsep and Mdr2 in the liver. RESULTS: The Liver function of TAA group rats was severely injured [ALT(524.0±32.0) vs (28.3±8.4) U/L]. It was worsen by application of sodium hydrosulfide [ALT(861.9±55.1) U/L] while recovered [ALT(59.5±10.2) U/L)] by propargylglycine. The level of bilirubin and bile acid was significantly higher in the TAA group rats than in the normal control group, and the application of sodium hydrosulfide caused bile acids increased further besides of bilirubin. On the contrary, the levels of bile acids and bilirubin were significantly decreased with PPG application. The level of hydrogen sulfide in the serum of the TAA group rats was higher than normal group rats'. That was elevated by sodium hydrosulfide and decreased by propargylglycine.Severely edema, necrosis and inflammatory cell infiltration were observed in TAA group rats, which worse by sodium hydrosulfide and released by propargylglycine. The expression of Bsep and Mdr2 down regulated in TAA and deteriorated by sodium hydrosulfide application and relieved by propargylglycine application. CONCLUSION: Hydrogen sulfide exacerbated the Bsep and Mdr2 loss in the liver failure and contributed to high serum concentration of bile acids.