Objective To probe into the effective acupuncture treatment for high fever and other clinical relevant symptoms in common cold. Methods Based on randoming and multi-central clinical trial principle, the included 276 c...Objective To probe into the effective acupuncture treatment for high fever and other clinical relevant symptoms in common cold. Methods Based on randoming and multi-central clinical trial principle, the included 276 cases were randomized into experimental group (138 cases) and control group (138 cases) in statistics. Electric acupuncture on Dazhui(大椎 GV14) was applied in experimental group and the injection with antondine was in control group. The immediate antipyretic and clinical therapeutic effects were observed in 24 h. Results The body temperatures at different times in experimental group were all lower than those in control group after treatment (P〈 0.01 ). The scores of relevant symptoms in 3- 24 h after treatment were lower than those in control group (P〈0.05). The response time (1.42± 1.79) h in experimental group was shorter than that (3.44±5.10) h in control group (P〈0.05). The response times for chills, soreness of limbs, headach and sweating in experimental group were shorter than those in control group (P〈0. 01 ). The recovery times for chills and headache in experimental group were shorter than those in control group (P〈0.05). The systematic therapeutic effects were different significantly between two groups in 24 h (P〈0.05). Conclusion Acupuncture on Dazhui(大椎 GV14) had achieved definite effects on treatment for high fever in common cold. It released remarkably chills, soreness of limbs, headache and sweating and improved the systematic therapeutic effects on common cold.展开更多
AIM: To evaluate the antibacterial activity of Sapindus mukorossi (S. mukorossl) and Rheum emodi (R. emodl). METHODS: Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzen...AIM: To evaluate the antibacterial activity of Sapindus mukorossi (S. mukorossl) and Rheum emodi (R. emodl). METHODS: Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylon, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram +ve (S. aureus, B. subtilis) and two Gram -ve (E. coli, P. vugaris) organisms were screened for their susceptibility patterns against these extracts. RESULTS: In our screening, all 30 resistant isolates and the other four organisms (two Gram +ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris) were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited Hpylori at very low concentrations, In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations (10 μg/mL) for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi (2.5 mg/mL) and R. emodi (3.0 mg/mL) given orally for seven days. CONCLUSION: We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages.展开更多
AIM: To study the hepatoprotective capacity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi) extracts in CCl4 treated male rats. METHODS: The dried powder of S. mukorossi and R. emodi was extracted succ...AIM: To study the hepatoprotective capacity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi) extracts in CCl4 treated male rats. METHODS: The dried powder of S. mukorossi and R. emodi was extracted successively with petroleum ether, benzene, chloroform, and ethanol and concentrated in vacuum. Primary rat hepatocyte monolayer cultures were used for in vitro studies. In vivo, the hepatoprotective capacity of the extract of the fruit pericarp of S. mukorossi and the rhizomes of R. emodi was analyzed in liver injured CCl4-treated male rats. RESULTS: In vitro: primary hepatocytes monolayer cultures were treated with CCl4 and extracts of S. mukorossi & R. emodi. A protective activity could be demonstrated in the CCl4 damaged primary monolayer culture. In vivo : extracts of the fruit pericarp of S. mukorossi (2.5 mg/mL) and rhizomes of R. emodi (3.0 mg/mL) were found to have protective properties in rats with CCl4 induced liver damage as judged from serum marker enzyme activities. CONCLUSION: The extracts of S. mukorossi and R. emodi do have a protective capacity both in vitro on primary hepatocytes cultures and in in vivo in a rat model of CCl4 mediated liver injury.展开更多
Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, prom...Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several protooncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and microRNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be selected for combined regiments. However, due to its context-dependent cellular function, it is clinically essential to consider which cytotoxic drugs are used in combination with c-MYC targeted agents in various tissues. Increasing our knowledge about MYCdependent pathways might provide direction to novel anti-inflammatory and colorectal cancer therapies.展开更多
Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the cr...Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel a-helices, dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.展开更多
The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regul...The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.展开更多
ObjectiveTo validate a modified HEART [History, Electrocardiograph (ECG), Age, Risk factors and Troponin] risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS...ObjectiveTo validate a modified HEART [History, Electrocardiograph (ECG), Age, Risk factors and Troponin] risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in the emergency department (ED).Methods This retrospective cohort study used a prospectively acquired database and chest pain patients admitted to the emergency department with suspected NSTE-ACS were enrolled. Data recorded on arrival at the ED were used. The serum sample of high-sensitivity cardiac Troponin I other than conventional cardiac Troponin I used in the HEART risk score was tested. The modified HEART risk score was calculated. The end point was the occurrence of major adverse cardiac events (MACE) defined as a composite of acute myocardial infarction (AMI), percu-taneous intervention (PCI), coronary artery bypass graft (CABG), or all-cause death, within three months after initial presentation.Results A total of 1,300 patients were enrolled. A total of 606 patients (46.6%) had a MACE within three months: 205 patients (15.8%) were diag-nosed with AMI, 465 patients (35.8%) underwent PCI, and 119 patients (9.2%) underwent CABG. There were 10 (0.8%) deaths. A progres-sive, significant pattern of increasing event rate was observed as the score increased (P < 0.001 byχ2 for trend). The area under the receiver operating characteristic curve was 0.84. All patients were classified into three groups: low risk (score 0-2), intermediate risk (score 3-4), and high risk (score 5-10). Event rates were 1.1%, 18.5%, and 67.0%, respectively (P < 0.001).ConclusionsThe modified HEART risk score was validated in chest pain patients with suspected NSTE-ACS and may complement MACE risk assessment and patients triage in the ED. A prospective study of the score is warranted.展开更多
To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients.METHODSDuring a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, I...To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients.METHODSDuring a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury.RESULTSTwo hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued.CONCLUSIONLiver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.展开更多
To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. METHODSColonic mucosal pinch biopsies were analyzed from the i...To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. METHODSColonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted. RESULTSThe miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC. CONCLUSIONThe present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.展开更多
Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients, but the economic perspectives can provide important data to make inform...Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients, but the economic perspectives can provide important data to make informed decisions. This study aimed to perform the economic evaluation of lifelong annual influenza vaccination for cardiovascular events and well-established pneumonia prevention. Methods Lifetime costs, life-expectancy, and quality-adjusted live years (QALYs) were estimated beyond one-year cycle length of a six-health states Markov model condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia, no hospitalizations occurred, or death. The comparison of three age-groups of 40-49, 50-65, and 〉 65 years scenario was performed. Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were presented as a societal perspective in 2016. The model robustness was determined by one-way and prob- abilistic sensitivity analyses. Results The influenza vaccination was cost-effective in all age-groups, by dominant ICERs (lower cost with higher effectiveness) which was completely lower than acceptable willingness-to-pay threshold of Thailand [160,000 THB (4,466.8 USD) per QALYs], with a great incremental value of NMB. Especially, the 50-year-old-and- above scenario was shown as the most benefit at 129,092 THB (3,603.9 USD) for each patient. Conclusions The annually additional influenza vaccination to standard treatment in ACS was cost-effective in all age-groups, which should be considered in clinical practice and health-policy making process.展开更多
The antiviral activity in vitro and in vivo and the effect of the immune system of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica(LMW fucoidans) were investigate...The antiviral activity in vitro and in vivo and the effect of the immune system of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica(LMW fucoidans) were investigated in order to examine the possible mechanism. In vitro, I-type influenza virus, adenovirus and Parainfluenza virus I were used to infect Hep-2, Hela and MDCK cells, respectively. And 50% tissue culture infective dose was calculated to detect the antiviral activity of two LMW fucoidans. The results indicated that compared with the control group, 2 kinds of LMW fucoidans had remarkable antiviral activity in vitro in middle and high doses, while at low doses, the antiviral activity of 2 kinds of LMW fucoidans was not statistically different from that in the blank control group. And there was no statistically difference between two LMW fucoidans in antiviral activity. In vivo, LMW fucoidans could prolong the survival time of virus-infected mice, and could improve the lung index of virus-infected mice significantly, which have statistical differences with the control group significantly(p < 0.01). However, the survival time of the two LMW fucoidans was not statistically significant(p > 0.05). In this study, it was shown that both of two LMW fucoidans(LF1, LF2) could increase the thymus index, spleen index, phagocytic index, phagocytosis coefficient and half hemolysin value in middle and high doses, which suggested that LMW fucoidans could play an antiviral role by improving the quality of immune organs, improving immune cell phagocytosis and humoral immunity.展开更多
Failure of the surrounding rock around a roadway induced by roof separation is one major type of underground roof-fall accidents.This failure can especially be commonly-seen in a bottom-driven roadway within an extra-...Failure of the surrounding rock around a roadway induced by roof separation is one major type of underground roof-fall accidents.This failure can especially be commonly-seen in a bottom-driven roadway within an extra-thick coal seam("bottom-driven roadway"is used throughout for ease of reference),containing weak partings in their roof coal seams.To determine the upper limit position of the roof interlayer separation is the primary premise for roof control.In this study,a mechanical model for predicting the interlayer separation overlying a bottom-driven roadway within an extra-thick coal seam was established and used to deduce the vertical stress,and length,of the elastic,and plastic zones in the rock strata above the wall of the roadway as well as the formulae for calculating the deflection in different regions of rock strata under bearing stress.Also,an approach was proposed,calculating the stratum load,deflection,and limiting span of the upper limit position of the interlayer separation in a thick coal seam.Based on the key strata control theory and its influence of bedding separation,a set of methods judging the upper limit position of the roof interlayer separation were constructed.In addition,the theoretical prediction and field monitoring for the upper limit position of interlayer separation were conducted in a typical roadway.The results obtained by these two methods are consistent,indicating that the methods proposed are conducive to improving roof control in a thick coal seam.展开更多
The bending stresses of top tensioned riser(TTR) under combined excitations of currents,random waves and vessel motions are presented in this paper,and the effect of the internal flowing fluid on the riser stresses is...The bending stresses of top tensioned riser(TTR) under combined excitations of currents,random waves and vessel motions are presented in this paper,and the effect of the internal flowing fluid on the riser stresses is also considered.The computation programs which are used to solve the differential equations in the time domain are compiled and the principal factors of concern including the angular movements at the upper and lower ends of the riser,lateral displacements and bending stresses are presented.Then the effects of current velocity,random wave,top tension,vessel mean offset,low frequency motion and internal flow velocity on the bending stresses of the riser are analyzed in detail.展开更多
Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and int...Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis.展开更多
Ischemic colitis can mimic a carcinoma on computed tomographic (CT) imaging or endoscopic examination. A coexisting colonic carcinoma or another potentially obstructing lesion has also been described in 20% of the cas...Ischemic colitis can mimic a carcinoma on computed tomographic (CT) imaging or endoscopic examination. A coexisting colonic carcinoma or another potentially obstructing lesion has also been described in 20% of the cases of ischemic colitis. CT scan can differentiate it from colon cancer in 75% of cases. However, colonoscopy is the preferred method for diagnosing ischemic colitis as it allows for direct visualization with tissue sampling. Varied presentations of ischemic colitis have been described as an ulcerated or submucosal mass or as a narrowed segment of colon with ulcerated mucosa on colonoscopy. Awareness and early recognition of such varied presentations of a common condition is necessary to differentiate from a colonic carcinoma, and to avoid unnecessary surgery and related complications.展开更多
文摘Objective To probe into the effective acupuncture treatment for high fever and other clinical relevant symptoms in common cold. Methods Based on randoming and multi-central clinical trial principle, the included 276 cases were randomized into experimental group (138 cases) and control group (138 cases) in statistics. Electric acupuncture on Dazhui(大椎 GV14) was applied in experimental group and the injection with antondine was in control group. The immediate antipyretic and clinical therapeutic effects were observed in 24 h. Results The body temperatures at different times in experimental group were all lower than those in control group after treatment (P〈 0.01 ). The scores of relevant symptoms in 3- 24 h after treatment were lower than those in control group (P〈0.05). The response time (1.42± 1.79) h in experimental group was shorter than that (3.44±5.10) h in control group (P〈0.05). The response times for chills, soreness of limbs, headach and sweating in experimental group were shorter than those in control group (P〈0. 01 ). The recovery times for chills and headache in experimental group were shorter than those in control group (P〈0.05). The systematic therapeutic effects were different significantly between two groups in 24 h (P〈0.05). Conclusion Acupuncture on Dazhui(大椎 GV14) had achieved definite effects on treatment for high fever in common cold. It released remarkably chills, soreness of limbs, headache and sweating and improved the systematic therapeutic effects on common cold.
文摘AIM: To evaluate the antibacterial activity of Sapindus mukorossi (S. mukorossl) and Rheum emodi (R. emodl). METHODS: Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylon, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram +ve (S. aureus, B. subtilis) and two Gram -ve (E. coli, P. vugaris) organisms were screened for their susceptibility patterns against these extracts. RESULTS: In our screening, all 30 resistant isolates and the other four organisms (two Gram +ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris) were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited Hpylori at very low concentrations, In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations (10 μg/mL) for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi (2.5 mg/mL) and R. emodi (3.0 mg/mL) given orally for seven days. CONCLUSION: We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages.
文摘AIM: To study the hepatoprotective capacity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi) extracts in CCl4 treated male rats. METHODS: The dried powder of S. mukorossi and R. emodi was extracted successively with petroleum ether, benzene, chloroform, and ethanol and concentrated in vacuum. Primary rat hepatocyte monolayer cultures were used for in vitro studies. In vivo, the hepatoprotective capacity of the extract of the fruit pericarp of S. mukorossi and the rhizomes of R. emodi was analyzed in liver injured CCl4-treated male rats. RESULTS: In vitro: primary hepatocytes monolayer cultures were treated with CCl4 and extracts of S. mukorossi & R. emodi. A protective activity could be demonstrated in the CCl4 damaged primary monolayer culture. In vivo : extracts of the fruit pericarp of S. mukorossi (2.5 mg/mL) and rhizomes of R. emodi (3.0 mg/mL) were found to have protective properties in rats with CCl4 induced liver damage as judged from serum marker enzyme activities. CONCLUSION: The extracts of S. mukorossi and R. emodi do have a protective capacity both in vitro on primary hepatocytes cultures and in in vivo in a rat model of CCl4 mediated liver injury.
文摘Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several protooncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and microRNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be selected for combined regiments. However, due to its context-dependent cellular function, it is clinically essential to consider which cytotoxic drugs are used in combination with c-MYC targeted agents in various tissues. Increasing our knowledge about MYCdependent pathways might provide direction to novel anti-inflammatory and colorectal cancer therapies.
文摘Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel a-helices, dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.
基金Supported by A Grant from Agenzia Italiana del Farmaco(AIFA) grant code FARM6FJ728
文摘The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.
文摘ObjectiveTo validate a modified HEART [History, Electrocardiograph (ECG), Age, Risk factors and Troponin] risk score in chest pain patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in the emergency department (ED).Methods This retrospective cohort study used a prospectively acquired database and chest pain patients admitted to the emergency department with suspected NSTE-ACS were enrolled. Data recorded on arrival at the ED were used. The serum sample of high-sensitivity cardiac Troponin I other than conventional cardiac Troponin I used in the HEART risk score was tested. The modified HEART risk score was calculated. The end point was the occurrence of major adverse cardiac events (MACE) defined as a composite of acute myocardial infarction (AMI), percu-taneous intervention (PCI), coronary artery bypass graft (CABG), or all-cause death, within three months after initial presentation.Results A total of 1,300 patients were enrolled. A total of 606 patients (46.6%) had a MACE within three months: 205 patients (15.8%) were diag-nosed with AMI, 465 patients (35.8%) underwent PCI, and 119 patients (9.2%) underwent CABG. There were 10 (0.8%) deaths. A progres-sive, significant pattern of increasing event rate was observed as the score increased (P &lt; 0.001 byχ2 for trend). The area under the receiver operating characteristic curve was 0.84. All patients were classified into three groups: low risk (score 0-2), intermediate risk (score 3-4), and high risk (score 5-10). Event rates were 1.1%, 18.5%, and 67.0%, respectively (P &lt; 0.001).ConclusionsThe modified HEART risk score was validated in chest pain patients with suspected NSTE-ACS and may complement MACE risk assessment and patients triage in the ED. A prospective study of the score is warranted.
文摘To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients.METHODSDuring a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury.RESULTSTwo hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued.CONCLUSIONLiver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.
基金Supported by Department of Biotechnology,Ministry of Science and Technology,New Delhi,Government of India vide BT/PR8348/MED/30/1023/2013 to Paul JPURSE grant from the Department of Science and Technology,New Delhi India vide 6(54)SLS/JP/DST PURSE/2015-2016
文摘To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients. METHODSColonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted. RESULTSThe miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC. CONCLUSIONThe present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.
文摘Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients, but the economic perspectives can provide important data to make informed decisions. This study aimed to perform the economic evaluation of lifelong annual influenza vaccination for cardiovascular events and well-established pneumonia prevention. Methods Lifetime costs, life-expectancy, and quality-adjusted live years (QALYs) were estimated beyond one-year cycle length of a six-health states Markov model condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia, no hospitalizations occurred, or death. The comparison of three age-groups of 40-49, 50-65, and 〉 65 years scenario was performed. Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were presented as a societal perspective in 2016. The model robustness was determined by one-way and prob- abilistic sensitivity analyses. Results The influenza vaccination was cost-effective in all age-groups, by dominant ICERs (lower cost with higher effectiveness) which was completely lower than acceptable willingness-to-pay threshold of Thailand [160,000 THB (4,466.8 USD) per QALYs], with a great incremental value of NMB. Especially, the 50-year-old-and- above scenario was shown as the most benefit at 129,092 THB (3,603.9 USD) for each patient. Conclusions The annually additional influenza vaccination to standard treatment in ACS was cost-effective in all age-groups, which should be considered in clinical practice and health-policy making process.
基金supported by grants from the Technology Development Project (No. 201505022)the NSFC Shandong Joint Fund (No. U1406402)National Natural Science Foundation of China (No. 31371759)
文摘The antiviral activity in vitro and in vivo and the effect of the immune system of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica(LMW fucoidans) were investigated in order to examine the possible mechanism. In vitro, I-type influenza virus, adenovirus and Parainfluenza virus I were used to infect Hep-2, Hela and MDCK cells, respectively. And 50% tissue culture infective dose was calculated to detect the antiviral activity of two LMW fucoidans. The results indicated that compared with the control group, 2 kinds of LMW fucoidans had remarkable antiviral activity in vitro in middle and high doses, while at low doses, the antiviral activity of 2 kinds of LMW fucoidans was not statistically different from that in the blank control group. And there was no statistically difference between two LMW fucoidans in antiviral activity. In vivo, LMW fucoidans could prolong the survival time of virus-infected mice, and could improve the lung index of virus-infected mice significantly, which have statistical differences with the control group significantly(p < 0.01). However, the survival time of the two LMW fucoidans was not statistically significant(p > 0.05). In this study, it was shown that both of two LMW fucoidans(LF1, LF2) could increase the thymus index, spleen index, phagocytic index, phagocytosis coefficient and half hemolysin value in middle and high doses, which suggested that LMW fucoidans could play an antiviral role by improving the quality of immune organs, improving immune cell phagocytosis and humoral immunity.
基金Project(2017XKQY012) supported by the Fundamental Research Funds for the Central Universities,ChinaProject(PAPD) supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions,China
文摘Failure of the surrounding rock around a roadway induced by roof separation is one major type of underground roof-fall accidents.This failure can especially be commonly-seen in a bottom-driven roadway within an extra-thick coal seam("bottom-driven roadway"is used throughout for ease of reference),containing weak partings in their roof coal seams.To determine the upper limit position of the roof interlayer separation is the primary premise for roof control.In this study,a mechanical model for predicting the interlayer separation overlying a bottom-driven roadway within an extra-thick coal seam was established and used to deduce the vertical stress,and length,of the elastic,and plastic zones in the rock strata above the wall of the roadway as well as the formulae for calculating the deflection in different regions of rock strata under bearing stress.Also,an approach was proposed,calculating the stratum load,deflection,and limiting span of the upper limit position of the interlayer separation in a thick coal seam.Based on the key strata control theory and its influence of bedding separation,a set of methods judging the upper limit position of the roof interlayer separation were constructed.In addition,the theoretical prediction and field monitoring for the upper limit position of interlayer separation were conducted in a typical roadway.The results obtained by these two methods are consistent,indicating that the methods proposed are conducive to improving roof control in a thick coal seam.
基金supported by the High Technology Research and Development Program of China (863 Program, Grant Nos SQ2009AA09Z3487852 and 2007AA09Z313)
文摘The bending stresses of top tensioned riser(TTR) under combined excitations of currents,random waves and vessel motions are presented in this paper,and the effect of the internal flowing fluid on the riser stresses is also considered.The computation programs which are used to solve the differential equations in the time domain are compiled and the principal factors of concern including the angular movements at the upper and lower ends of the riser,lateral displacements and bending stresses are presented.Then the effects of current velocity,random wave,top tension,vessel mean offset,low frequency motion and internal flow velocity on the bending stresses of the riser are analyzed in detail.
文摘Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis.
文摘Ischemic colitis can mimic a carcinoma on computed tomographic (CT) imaging or endoscopic examination. A coexisting colonic carcinoma or another potentially obstructing lesion has also been described in 20% of the cases of ischemic colitis. CT scan can differentiate it from colon cancer in 75% of cases. However, colonoscopy is the preferred method for diagnosing ischemic colitis as it allows for direct visualization with tissue sampling. Varied presentations of ischemic colitis have been described as an ulcerated or submucosal mass or as a narrowed segment of colon with ulcerated mucosa on colonoscopy. Awareness and early recognition of such varied presentations of a common condition is necessary to differentiate from a colonic carcinoma, and to avoid unnecessary surgery and related complications.