PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.

Purpose:Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. METHODS: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. RESULTS: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. CONCLUSION: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.

Natural phytoalexins inspired the discovery of new biphenyls as potent antifungal agents for treatment of invasive fungal infections.

With the aim of discovering novel and effective antifungal agents derived from natural sources, a series of new biphenyls based on natural biphenyl phytoalexins were designed, synthesized and evaluated for their antifungal activities against four invasive fungi. By modifying the two benzene rings of noraucuparin, a well-known biphenyl phytoantitoxin, some promising compounds with remarkable antifungal activity were discovered. Notably, compounds 23a, 23e and 23h exhibited potent activities and a broad antifungal spectrum with low MICs of 0.25-16 µg/mL, which were 8-256-fold more potent than that of the lead compound noraucuparin. Particularly, they displayed comparable potency to the positive control amphotericin B against Cryptococcus neoformans. Some interesting structure-activity relationships have also been discussed. Preliminary mechanism studies revealed that compound 23h might achieve its rapid fungicidal activity by disrupting the fungal cell membrane. Moreover, compound 23h exhibited significant inhibition against some virulence factors of Cryptococcus neoformans, low toxicity to normal human cells, as well as favorable pharmacokinetic and drug-like properties. The above results evidenced that the development of new antifungal candidates derived from natural phytoalexins was a bright and promising strategy.

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). METHODS: This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. RESULTS: The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. CONCLUSION: Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).

Correlation of Glucose Metabolism with Cancer and Intervention with Traditional Chinese Medicine.

Cancer is a complex disease with several distinct characteristics, referred to as "cancer markers" one of which is metabolic reprogramming, which is a common feature that drives cancer progression. Over the last ten years, researchers have focused on the reprogramming of glucose metabolism in cancer. In cancer, the oxidative phosphorylation metabolic pathway is converted into the glycolytic pathway in order to meet the growth requirements of cancer cells, thereby creating a microenvironment that promotes cancer progression. The precise mechanism of glucose metabolism in cancer cells is still unknown, but it is thought to involve the aberrant levels of metabolic enzymes, the influence of the tumor microenvironment (TME), and the activation of tumor-promoting signaling pathways. It is suggested that glucose metabolism is strongly linked to cancer progression because it provides energy to cancer cells and interferes with antitumor drug pharmacodynamics. Therefore, it is critical to unravel the mechanism of glucose metabolism in tumors in order to gain a better understanding of tumorigenesis and to lay the groundwork for future research into the identification of novel diagnostic markers and therapeutic targets for cancer treatment. Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, multiple components, and less toxic side effects and has unique advantages in tumor treatment. In recent years, researchers have found that a variety of Chinese medicine monomers and compound recipes play an antitumor role by interfering with the reprogramming of tumor metabolism. The underlying mechanisms of metabolism reprogramming of tumor cells and the role of TCM in regulating glucose metabolism are reviewed in this study, so as to provide a new idea for antitumor research in Chinese medicine.

Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.

OBJECTIVE: To investigate the protective effects and molecular mechanisms of Lizhong decoction (, LZD) against non-alcoholic fatty liver disease (NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined. RESULTS: Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage, inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor (PPAR)-γ expression, and suppressed dipeptidyl peptidase 4 (DPP4) expression in the liver. CONCLUSION: It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.

Identifying Active Substances and the Pharmacological Mechanism of Houttuynia cordata Thunb. in Treating Radiation-Induced Lung Injury Based on Network Pharmacology and Molecular Docking Verification.

Background: Houttuynia cordata Thunb. is a traditional Chinese herb widely used mainly because of the pharmacological effects related to heat clearance and detoxification. Emerging clinical evidence indicates that the efficacy of Houttuynia cordata Thunb. on RILI is upstanding. Nevertheless, its underlying therapeutic mechanism remains unclear and warrants further elucidation. Methods: The major active components and corresponding targets of Houttuynia cordata Thunb. were retrieved from the traditional Chinese medicine system pharmacology database (TCMSP) and literature review. The related targets of RILI were retrieved from the GeneCards database. Common targets among the active compounds and diseases were identified through Venn diagram analysis. Cytoscape was employed to construct and visualize the network relationship among the drug, active compounds, targets, and disease. The protein interaction network (PPI) was constructed by STRING. The reliability (the binding affinity) of the core targets and active compounds was verified by molecular docking. Results: A search of the TCMSP database and related literature revealed 12 active compounds of Houttuynia cordata Thunb. against RILI. The core active compounds included quercetin, kaempferol, hyperoside, and rutin. Hub nodes including TP53, VEGFA, JUN, TNF, and IL-6 were identified in the PPI network. The GO categories were classified into three functional categories: 112 biological processes, 9 molecular functions, and 32 cellular components of the active compounds of Houttuynia cordata Thunb. The KEGG pathway enrichment analysis demonstrated the enrichment of target genes in several key cancer-related signaling pathways, including the cancer pathways, TNF signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. Molecular docking analysis validated the effective binding capacity of the main active compounds with the core targets. Conclusion: The main active components of Houttuynia cordata Thunb. have a potential pharmacological effect against RILI via the cancer pathways, TNF signaling pathway, and PI3K-Akt signaling pathway.

[Electroacupuncture in the treatment of acute gastrointestinal injury in patients with severe traumatic brain injury: a prospective randomized controlled trial].

OBJECTIVE: To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI). METHODS: A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis. RESULTS: During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH2O, 1 cmH2O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH2O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH2O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ2 = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment. CONCLUSIONS: Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.

Use of Traditional Chinese Herbal Medicine Concurrently with Conventional Cancer Treatment Among Chinese Cancer Patients.

In the U.S. and Canada, Traditional Chinese Medicine (TCM) use has become increasingly common; Chinese immigrants have particularly high rates of TCM use. In this study, we used a cross sectional survey study design to assess the specific types of Traditional Chinese Herbal Medicine (TCHM) used, the concurrent use of TCHM and conventional cancer treatment, and communication with providers about TCHM use, among Chinese immigrant cancer patients in New York City (NYC). We surveyed 114 patients from several community and clinical settings in NYC. The mean age was 63, 59% were female, and 83% originated from mainland China. Breast (18%) and lung (21%) cancer were the most common cancer diagnoses, and 60% were receiving conventional cancer treatment at the time of the survey. 75% reported ever using TCHM since their most recent primary cancer diagnosis. 68% of those who used herbs reported concurrent use of TCHM with conventional cancer treatment. Only 13% of those who used herbs reported sharing TCHM use with a provider, and only 19% reported that a provider had ever discussed TCHM use with them. Our findings demonstrated an alarmingly high rate of concurrent use of TCHM and conventional cancer treatment and low rate of communication with providers about TCHM use. A wide variety of herbs were used, including those with potentially negative interactions with conventional treatment. This study highlights the urgent need for the development of interventions to assist providers and patients in improving communication around this important topic.

Traditional Chinese medicine bundle therapy for septic acute gastrointestinal injury: A multicenter randomized controlled trial.

OBJECTIVE: Current conventional treatments for sepsis associated with acute gastrointestinal injury (AGI) have limited efficacy. This study aimed to study traditional Chinese medicine (TCM) bundle therapy (based on TCM syndrome differentiation) as add-on to conventional treatments on the incidence of AGI and on the prognosis of patients with sepsis. DESIGN: This was a prospective multicenter randomized single-blind controlled trial. SETTING: Intensive care units (ICUs) of five university teaching hospitals in Zhejiang Province (China) from December 2012 to December 2014. INTERVENTIONS: The control group received conventional treatment for sepsis and AGI. The intervention group received the conventional treatment combined with TCM bundle therapy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day mortality. The secondary outcomes included the clinical indicators of sepsis. The 28-day mortality (35.3% vs. 48.3%, P = 0.01) and AGI-attributable mortality (15.1% vs. 36.2%, P = 0.02) in the intervention group were significantly lower than in controls. Duration of mechanical ventilation (17.4 ±â€¯10.4 vs. 19.9 ±â€¯11.1 days, P = 0.049) and duration of ICU stay (17.3 ±â€¯10.2 vs. 20.1 ±â€¯11.5 days) were significantly shorter in the intervention group compared with controls. On days 7 and 14, D-lactate, diamine oxidase, lipopolysaccharides, tumor necrosis factor-α, intra-abdominal pressure, and abdominal circumference in the intervention group were significantly lower than in controls, and serum MTL levels and bowel sounds were significantly higher (all P < 0.05). CONCLUSIONS: TCM bundle therapy in the early stage of sepsis can improve survival and the markers of gastrointestinal function in patients with sepsis associated with AGI.

Systemic air embolism in a fungal pneumonia patient with lung cavities formation and review of literature.

Systemic air embolism is a rare but potentially fatal complication related to many factors. The purpose of this article is to alert clinicians once patients occurs an abnormal neurological and cardiovascular status, following minor traumatic treatment, air embolism should be considered. A 20-year-old man who presented with fungal pneumonia with lung cavities formation was admitted to an intensive care unit (ICU) and received positive airway pressure ventilation. Four days later, the fungal pneumonia was improved, but the patient's blood pressure and arterial oxygen saturation deteriorated, so computed tomography (CT) scans were preformed to reevaluate him. The scans detected air embolism in the left atrium and ventricle, ascending aorta, aortic arch and its branches (right brachiocephalic, bilateral common carotid and right subclavian arteries), descending aorta and right coronary artery. A CT scan of the abdomen revealed air in the spleen, cauda pancreatic, superior mesenteric artery and right external iliac artery. The patient died two days later from multiple organ dysfunction. We suggest that vascular air embolism should be considered under mechanical ventilation when patients' neurologic and cardiovascular status deteriorates, and hyperbaric oxygen therapy should be conducted immediately.

[Intervention effects and mechanism of Chinese herbal medicine of supplementing Qi and activating blood circulation on chronic intermittent hypoxia composite insulin resistance ApoE~(-/-) mice model].

This study aims to observe the intervention effects of Chinese herbal medicine of supplementing Qi and activating blood circulation on chronic intermittent hypoxia(CIH) composite insulin resistance(IR) mediated atherosclerosis(AS) mice model,and to observe the mechanism of SREBP-1 c signaling molecule.IR Apo E-/-mice model was induced by high-fat diet combined with STZ injection.Then the mice were treated with hypoxic animal incubator for 8 h per day and 8 weeks to establish a CIH+IR-ApoE-/-mouse model.Model mice were randomly and averagely divided into normoxic control group(NC),model group(CIH) and SREBPs inhibitor group(betulin),atorvastatin group(WM),TCM low-dose group(TCM-L),TCM middle-dose group(TCM-M) and TCM high-dose group(TCM-H) group.Chinese herbal medicine of supplementing Qi and activating blood circulation including ginsenosides combined with ligustrazine(TMP) were used as intervention drugs.The study observed the effect of drugs on IR,serum lipid,inflammation,stress,AS and SREBP-1 c related molecules.The results showed that fasting blood glucose in TCM-H group decreased compared with other experimental groups(P<0.05).HDL-C level in betulin group,WM group,TCM-H group was higher than that in CIH group(P<0.05).LDL-C level in TCM-M group,TCM-H group is lower than that in CIH group(P<0.05).The level of CRP in CIH group was higher than that in other groups(P<0.05).The level of SOD in TCM-H group was higher than that in CIH group(P<0.05).NC group and CIH group showed obvious AS aortic plaque,while betulin group,WM group,TCM-H group showed reduction in AS plaque(P<0.05).For descending aorta,AS plaque in CIH group was multiple and large,while less and smaller in WM group and TCM-H(P<0.05).The expression of SREBP-1 c and FAS in aorta and skeletal muscle in TCM-H group was lower than that in CIH group(P<0.05).In aorta,the expression of TNF-α and CD106(VCAM-1) was lower in TCM-H group than that in CIH group(P<0.05).In aorta,skeletal muscle and liver,the level of p-IRS-1 in TCM-H group was significantly higher than that in CIH group(P<0.05).In aorta and liver,the expression of HIF-1α in TCM-H group was lower than that in CIH group(P<0.05).The study demonstrated that combination ginsenosides with TMP could improve IR and serum lipid level and inhibit inflammation and oxidative stress as well as ultimately alleviate AS to some extent.And the mechanism of its interventional effects might be related to the inhibition of CIH-induced upregulation of SREBP-1 c related molecules.

Shenfu injection prolongs survival and protects the intestinal mucosa in rats with sepsis by modulating immune response.

BACKGROUND/AIMS: The aim of present study was to assess the protective effects of Shenfu injection (SI) on the intestinal mucosa and its regulation on the mucosal immune responses in rats with sepsis. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into the sham, model, low-dose SI (LSF), and high-dose SI (HSF) groups. Sham animals underwent laparotomy only, whereas sepsis was modeled by cecal ligation and puncture in the remaining groups. At 2 h post-surgery, the LSF and HSF groups were intraperitoneally administered 5 and 20 mL/kg SI, respectively, whereas other animals with saline. At 12 h and 24 h post-surgery, eight rats per group were sacrificed, and blood and intestinal tissues were collected. The intestinal mucosa was analyzed by hematoxylin and eosin staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations, as well as secretory immunoglobulin A (sIgA) content in the intestinal mucosa, were evaluated by enzyme-linked immunosorbent assay. CD3 and γδT lymphocytes were quantified by flow cytometry. Animal survival until 72 h was also recorded. RESULTS: Intestinal mucosal injury was significantly higher in model animals than in sham animals at postoperative 12 h and 24 h. Serum TNF-α and IL-6 levels were markedly increased, whereas sIgA and CD3 and γδT cell amounts were overtly decreased (p<0.01). The LSF and HSF rats showed lower mortality, intestinal mucosal injury, and serum TNF-α and IL-6 levels (p<0.05), as well as higher sIgA levels and CD3 and γδT cell amounts, than the model group (p<0.01), with a dose-dependent manner. CONCLUSION: SI dose-dependently prolongs survival and protects the intestinal mucosa in rats with sepsis, possibly through strengthening innate immunity instead of acquired immunity.

A putative 12-oxophytodienoate reductase gene CsOPR3 from Camellia sinensis, is involved in wound and herbivore infestation responses.

12-Oxophytodienoate reductase (OPR) is a key enzyme in the biosynthesis of jasmonic acid (JA), which plays an important role in plant defense responses. Although multiple isoforms of OPRs have been identified in various annual herbaceous plants, genes encoding these enzymes in perennial woody plants have yet to be fully investigated. In the tea plant, Camellia sinensis (L.), no OPR genes have been isolated, and their possible roles in tea plant development and defense mechanism remain unknown. In this study, a putative OPR gene, designated as CsOPR3, was isolated from tea plants for the first time through the rapid amplification of cDNA ends. The open reading frame of CsOPR3 is 1197bp in length, and encodes a protein of 398 amino acids. Real-time qPCR analysis revealed that CsOPR3 was expressed in different organs. In particular, CsOPR3 was highly expressed in flowers, leaves and stems but was weakly expressed in roots and seeds. CsOPR3 expression could be rapidly induced by mechanical wounding, and increased JA levels were correlated with the wound-induced CsOPR3 expression. The infestation of the tea geometrid (TG) Ectropis obliqua Prout, regurgitant derived from TG and exogenous JA application could enhance the CsOPR3 expression. Our study is the first to report that CsOPR3 plays an important role in JA biosynthesis and tea plant defense against herbivorous insects.

[Effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway].

This study aims to explore the intervention effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia(IH) induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway in vitro. HUVECs injury model was induced by modified IH treatment. The effective components of Chinese medicine of nourishing kidney and clearing liver including isochteroside, aucubin and ligustrazine were used as intervention drugs. The optimal compatibility concentration of them was screened in vitro, and then the optimal compatibility concentration was selected as the intervention dose to observe the effect on p38MAPK/NF-κB signaling pathway in IH induced injury model of HUVECs. The results showed that isochnae, aucubin and ligustrazine had the best anti-inflammatory effect at concentration of 0.01 mg•L-1. NF-κB p65 and p-IκB in the nucleus in IH group were significantly higher than those in the normal control(N) group and the other groups. Immunofluorescence staining showed significant translocation of NF-κB p65 nucleus in IH group, and HUVECs adhesion capacity in IH group was increased significantly. As compared with IH group, the expression levels of p-p38MAPK, NF-κB p65 and p-IκB in p38MAPK inhibitor(INH) group and Chinese medicine of nourishing kidney and clearing liver(GDC) group were significantly decreased, and HUVECs adhesion capacity in INH group and GDC group was significantly inhibited as well. The optimal concentration of Chinese medicine of nourishing kidney and clearing liver can inhibit the phosphorylation of p38MAPK, and then inhibit the nuclear translocation and transcription function of NF-κB. This may be the mechanism of the protective effect of Chinese medicine on IH induced injury model of HUVECs.

Electroacupuncture at Bilateral Zusanli Points (ST36) Protects Intestinal Mucosal Immune Barrier in Sepsis.

Sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Acupuncture has also been used widely for many years in China to treat sepsis. However, the underlying mechanisms are not well-defined. We demonstrated here that EA preconditioning at ST36 obviously ameliorated CLP-induced intestinal injury and high permeability and reduced the mortality of CLP-induced sepsis rats. Moreover, electroacupuncture (EA) pretreatment exerted protective effects on intestinal mucosal immune barrier by increasing the concentration of sIgA and the percentage of CD3+, γ/δ, and CD4+ T cells and the ratio of CD4+/CD8+ T cells. Although EA at ST36 treatments immediately after closing the abdomen in the CLP procedure with low-frequency or high-frequency could not reduce the mortality of CLP-induced sepsis in rats, these EA treatments could also significantly improve intestinal injury index in rats with sepsis and obviously protected intestinal mucosal immune barrier. In conclusion, our findings demonstrated that EA at ST36 could improve intestinal mucosal immune barrier in sepsis induced by CLP, while the precise mechanism underlying the effects needs to be further elucidated.

Shenfu injection alleviates intestine epithelial damage in septic rats.

BACKGROUND: Shenfu injection (SFI) promotes tissue microcirculation and oxygen metabolism. We aimed to assess its effects on intestinal epithelial damage in septic rats. METHODS: Fifty Sprague-Dawley rats were randomly divided into sham operation (Sham), sepsis (cecal ligation and puncture [CLP]), and SFI (low-dose, middle-dose, high-dose) groups (n = 10). For Sham animals, the abdominal cavity was opened and closed. For other groups, severe sepsis was induced by CLP. After surgery, saline (Sham and CLP rats) and SFI (treatment groups) were administered intraperitoneally. Samples were collected 12 hours after injection. Serum tumor necrosis factor α, diamineoxidase, and d-lactate levels and ileal mucosal damage and ultrastructural change, as well as protein and messenger RNA expression of tight junction markers, including Claudin-3 and zonula occludens protein-1 in ileal mucosa's epithelial cells, were assessed. All animal experiments were carried out under aseptic conditions. RESULTS: Compared with Sham animals, serum tumor necrosis factor α, DAO, and d-lactic acid levels in CLP animals were significantly higher; the ileal mucosal damage was more severe; and the expression levels of tight junction markers were significantly decreased. These indexes were significantly improved in SFI groups, in a concentration-dependent manner, compared with CLP rats. Sham animals displayed orderly arranged ileal mucosal villi, continuous tight junctions between epithelial cells, intact organelles, and microvilli. Compared with CLP animals (with obvious damage in these structures), an overt improvement was observed in SFI groups, especially in the high-dose SFI group, with tight junctions clearly visible between epithelial cells. CONCLUSIONS: Shenfu injection significantly alleviates intestinal epithelial damage in septic rats, in a dose-dependent manner.

Effect of Shenfu injection on intestinal mucosal barrier in a rat model of sepsis.

PURPOSE: The effects of Shenfu injection on protecting the intestinal mucosal barrier were investigated in rats with sepsis. METHODS: Severe sepsis was established by cecal ligation and puncture (CLP) in 30 healthy Sprague-Dawley rats. Twelve rats that received sham surgery received 10 mL/kg of normal saline. Rats with CLP were randomized to receive 10 mL/kg of normal saline (n = 12) and 5 mL/kg Shenfu (n = 12), and 10 received 10 mL/kg Shenfu injection (n = 12) by tail intravenous injection. Rats were killed after 8 hours. Serum levels of tumor necrosis factor α and interleukin-10, and ileal malondialdehyde and superoxide dismutase activity were measured by enzyme-linked immunosorbent assay. Ileum tissue structures and pathological score were observed by microscopy. Ileal mucosal epithelial cell apoptosis index was calculated by TUNEL assay. Ileal proapoptotic protein Bax, antiapoptotic protein Bcl-2, and tight junction transmembrane protein occludin were measured by immunohistochemistry and immunoblot. RESULTS: The level of tumor necrosis factor α, the ileal malondialdehyde level, ileum pathological score, apoptosis index of ileal mucosal epithelial cells, and Bax protein level were significantly higher, and serum level of interleukin-10, the ileal superoxide dismutase activity, Bcl-2 protein level, Bcl-2/Bax ratio, and occludin protein level were significantly lower in the CLP group than in the sham group (P < .01 or P < .05). Both low- and high-dose Shenfu significantly ameliorated these changes (P < .01 or P < .05), but high-dose injection achieved more significant improvements than did the low-dose injection (P < .01 or P < .05). CONCLUSIONS: Shenfu injection might ameliorate the mucosal barrier function in a model of sepsis in rats in a dose-dependent manner.

Gene-based association analysis identified novel genes associated with bone mineral density.

Genetic factors contribute to the variation of bone mineral density (BMD), which is a major risk factor of osteoporosis. The aim of this study was to identify more "novel" genes for BMD. Based on the publicly available SNP-based P values, we performed an initial gene-based analysis in a total of 32,961 individuals. Furthermore, we performed differential expression, pathway and protein-protein interaction analyses to find supplementary evidence to support the significance of the identified genes. About 21,695 genes for femoral neck (FN)-BMD and 21,683 genes for lumbar spine (LS)-BMD were analyzed using gene-based association analysis. A total of 35 FN-BMD associated genes and 53 LS-BMD associated genes were identified (P < 2.3×10(-6)) after Bonferroni correction. Among them, 64 genes have not been reported in previous SNP-based genome-wide association studies. Differential expression analysis further supported the significant associations of 14 genes with FN-BMD and 19 genes with LS-BMD. Especially, WNT3 and WNT9B in the Wnt signaling pathway for FN-BMD were further supported by pathway analysis and protein-protein interaction analysis. The present study took the advantage of gene-based association method to perform a supplementary analysis of the GWAS dataset and found some BMD-associated genes. The evidence taken together supported the importance of Wnt signaling pathway genes in determining osteoporosis. Our findings provided more insights into the genetic basis of osteoporosis.

[Effect of electro-acupuncture at zusanli (ST36) on the expression of ghrelin and HMGB1 in the small intestine of sepsis rats].

OBJECTIVE: To explore the expression of Ghrelin and high mobility group protein B1 (HMGB1) in the serum and the intestinal tissue of sepsis model rats, and to evaluate the effect of electro-acupuncture (EA) at Zusanli (ST36) on the expression of HMGB1 and Ghrelin. METHODS: Forty-eight male Wistar rats were randomly divided into four groups, i.e., the sham-operation (sham), the cecal ligation and puncture group (CLP), the CLP + EA at Zusanli (ST36) group (EA), and the CLP + Ghrelin receptor blocking agent + EA group (GHSRA), 12 in each group. A sepsis rat model was prepared by CLP. The incision of the abdominal wall was immediately sutured along the ventral midline for rats in the Sham group. In the EA group EA at Zusanli (ST36) was performed 20 min after CLP surgery with the constant voltage (2 - 100 Hz, 2 mA) for 30 min. In the GHSRA group, Ghrelin receptor blocking agent, [D-Arg1, D-Phe5, D-Trp79, Leu11]-substance P (700 nmol/kg), was administered through intravenous injection immediately after CLP, and 20 min later, EA at Zusanli (ST36) was performed in the same way as for rats in the EA group. Blood samples were withdrawn 12 h after CLP. The serum levels of Ghrelin and HMGB1 were detected using ELISA. Ghrelin expressions and the number of Ghrelin immunopositive cell in the jejunum were determined by immunohistochemistry. HMGB1 contents of the jejunum tissue were detected by Western blotting. RESULTS: Compared with the Sham group, the number of serum immunopositive cells and the expression of HMGB1 in the jejunum tissue significantly increased and levels of Ghrelin and the expression rate of immunopositive cells significantly decreased in the CLP group (P < 0.05). Compared with the CLP group, the number of serum immunopositive cells and the expression of HMGB1 in the jejunum tissue significantly decreased, but levels of Ghrelin and the expression rate of immunopositive cells significantly increased in the EA group (P < 0.05). Compared with the EA group, the number of serum immunopositive cells and the expression of HMGB1 in the jejunum tissue significantly increased in the GHSRA group (P < 0.05), but there was no statistical difference in levels of Ghrelin between the two groups (P > 0.05). The serum level of HMGB1 was negatively correlated with Ghrelin in the Sham group, the CLP group, and the EA group (r = -0. 528, P < 0.01). CONCLUSIONS: EA at Zusanli (ST36) could inhibit the expression of HMGB1 in the jejunum of septic rats, and promote the expression of Ghrelin. The expression of HMGB1 was inhibited by Ghrelin receptor blocking agent, which suggested that the anti-inflammation of EA at Zusanli (ST36) might be associated with Ghrelin.

Effect of high/low dose N-acetylcysteine on chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, characterised by persistent airflow limitation, mucus hypersecretion, oxidative stress and airway inflammation. N-acetylcysteine (NAC) have anti-oxidant and anti-inflammatory properties, which have been shown an uncertain benefit in COPD patients. METHOD: Systematic searches were conducted in Cochrane, Medline and Embase electronic databases. A meta-analysis was performed to evaluate the different effect between high and low-dose NAC treatment on COPD exacerbation. RESULTS: This review yielded 11 studies. The methodological quality of included studies were scored using the Jadad score, with a scale of 1 to 5 (score of 5 being the highest). Data showed high-dose NAC can reduce both the total number of exacerbations (RR = 0.59, 0.47 to 0.74, 95%CI, p < 0.001) and the proportion of patients with at least one exacerbation (RR = 0.76, 0.59 to 0.98, 95%CI, p = 0.03). In the low-dose group, subgroup with jadad ≤ 3 showed a significant decrease (RR = 0.69, 0.61 to 0.77, 95%CI, p < 0.001) in the proportion of patients with exacerbation, the other subgroup with Jadad score > 3 showed no significant decrease (RR = 0.98, 0.90 to 1.06, 95%CI, p = 0.59). And low-dose NAC showed no benefit in the total number of exacerbations (RR = 0.97, 0.68 to 1.37, 95%CI, p = 0.85). Neither high nor low-dose NAC treatment showed benefit in forced expiratory volume in one second(FEV1)(WMD = 1.08, -9.97 to 12.13, 95%CI, p = 0.85). CONCLUSION: Long-term high-dose NAC treatment may lead to a lower rate of exacerbations. But the effect of low-dose NAC treatment remains uncertain. Further researches are needed to confirm this outcome and to clarify its mechanisms.