Gene knockout or inhibition of macrophage migration inhibitory factor alleviates lipopolysaccharide-induced liver injury via inhibiting inflammatory response.

BACKGROUND: Liver injury is one of the most common complications during sepsis. Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine. This study explored the role of MIF in the lipopolysaccharide (LPS)-induced liver injury through genetically manipulated mouse strains. METHODS: The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were detected, and the expressions of MIF, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured. Liver histopathology was conducted to assess liver injury. Moreover, the inhibitions of MIF with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and 4-iodo-6-phenylpyrimidine (4-IPP) were used to evaluate their therapeutic potential of liver injury. RESULTS: Compared with wild-type mice, the liver function indices and inflammation factors presented no significant difference in the Mif-/- mice. After 72 h of the LPS-induced liver injury, serum levels of ALT, AST, and TBil as well as TNF-α and IL-1ß were significantly increased, but the knockout of Mif attenuated liver injury and inflammatory response. In liver tissue, mRNA levels of TNF-α, IL-1ß and NF-κB p65 were remarkably elevated in LPS-induced liver injury, while the knockout of Mif reduced these levels. Moreover, in LPS-induced liver injury, the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response. Importantly, compared to mice with LPS-induced liver injury, Mif knockout or MIF inhibitions significantly prolonged the survival of the mice. CONCLUSIONS: In LPS-induced liver injury, the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response, thereby prolonged the survival of the mice. Targeting MIF may be an important strategy to protect the liver from injury during sepsis.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Effects of Helicobacter pylori Infection on the Prognosis of Chronic Atrophic Gastritis by Inducing the Macrophage Polarization.

Background: Recently, the effects of Helicobacter pylori (H. pylori) infection on the prognosis of chronic atrophic gastritis (CAG) are still unclear. The aim of our study was to discuss the role of H. pylori infection on the prognosis of CAG by inducing the M1/M2 macrophage polarization. Methods: A total of 180 subjects as control (group 1), CAG patients without H. pylori infection (group 2) and H. pylori-associated CAG patients (group 3) were respectively recruited for this cross-sectional investigation in Daqing Oilfield General Hospital from May 2019 to July 2020. Their serum samples were collected to determine the concentrations of pro-inflammatory and anti-inflammatory cytokines. Meanwhile, the gastric mucosa was excised to determine the related gene expressions on the M1/M2 macrophage polarization. Then the prognosis of CAG was evaluated according to the status of clinical manifestations and endoscopic examination after the follow-up. Results: Notably, it was proved that compared with the control group, the expressions and concentrations of pro-inflammatory cytokines (M1 macrophage: inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6)) were significantly higher, while the anti-inflammatory cytokines (M2 macrophage: arginase-1 (Arg-1), IL-4 and IL-10) were apparently reduced in the group 2 and group 3 (P < 0.05). Moreover, more days were needed for the prognosis of CAG in group 3 than those in group 2, which was accompanied by higher expressions of pro-inflammatory and lower anti-inflammatory cytokines at the baseline (P < 0.05). Furthermore, negative correlations were shown between the concentrations of iNOS, TNF-α, IFN-γ and IL-6, and the prognosis of CAG (P < 0.05), while positive correlations were observed between the contents of IL-4 and IL-10, and prognosis of CAG (P < 0.05). Conclusion: These above results indicated that H. pylori infection-induced disorders of M1/M2 macrophage polarization could affect the prognosis of CAG.

Complete mitochondrial genome of Locusta migratoria migratoria (Orthoptera: Oedipodidae): three tRNA-like sequences on the N-strand.

The complete 16053 bp mitochondrial genome (mitogenome) sequence of Locusta migratoria migratoria has been determined. This mitogenome contains the base compositional biases and codon usage typical of metazoans, and the RSCU values indicate a negative correlation with the C and G contents in codon. The orientation and gene order of the L. migratoria migratoria is identical to Locusta migratoria migratoiodes. An unusual feature of the L. migratoria migratoria mitogenome is the presence of three tRNA-like structures on the N-strand: one tRNA(Ile)-like and two tRNA(Leu(CUN))-like sequences. The tRNA-like sequences have proper folding structures and anticodons sequences. Two repeated DNA sequences, Rpt I and Rpt II, were found in the A+T-rich region of the L. migratoria migratoria mitogenome. Both repeated sequences have various features. In the 5' region of Rpt I, a 51 bp fragment is localized in the srRNA gene; and there are two tandemly sub-repeated DNA sequences (sub-Rpts), Rpt 1-4, within Rpt I and Rpt II. One stem-loop structure on the N-strand that may be involved in the N-strand replication initiation was found in the A+T-rich region.

[The diagnostic value of MSCT multi-dimensional reconstructions for congenital vascular ring with tracheal stenosis].

OBJECTIVE: To evaluate the diagnostic value of multi-slice CT (MSCT) reconstructions for congenital vascular rings together with tracheal stenosis. METHODS: 9 cases of children with congenital vascular ring and tracheal stenosis confirmed by surgery were collected in the study, all cases had undergone thin slice CT contrast enhancement, the MSCT data were transmitted to the workstation for multiplanar reconstruction (MPR), volume rendering technique (VRT) and VR transparency reconstruction. With the surgical results as the gold standard, the imaging characteristics of echocardiography (UCG) and MSCT were comparatively analyzed. RESULTS: In 9 cases, there were 4 cases of pulmonary artery sling, 3 cases of right aortic arch combination with left aberrant subclavian artery, 1 case of double aortic arch, 1 case of innominate artery compression syndrome. In this group, 5 cases were accompanied with other cardiac malformations (tetralogy of Fallot in 2 cases, double outlet right ventricle with patent ductus arteriosus and ventricular septal defect in 1 case, ventricular septal defect in 1 case, double superior vena cava in 1 case), 1 case of tetralogy of Fallot demonstrated many tortuous collateral arteries around aorta. All malformations were well displayed by VRT, MPR. VR transparency reconstruction can stereoscopically display trachea and bronchial compression condition, the main trachea was compressed in 6 cases, the main trachea and left main bronchus was compressed in 2 cases, the main trachea and left main bronchus was compressed in 1 cases, UCG detected all intracardiac malformations, 1 case of pulmonary artery sling was misdiagnosed as patent ductus arteriosus, 8 cases of vascular rings, tracheal and bronchial stenosis were missed. CONCLUSION: MSCT reconstruction technology is a noninvasive, rapid diagnostic method, it can clearly show the congenital vascular rings abnormalities and the degree of tracheal stenosis, it has important significance for clinic treatment.

Clinical Characteristics and Contemporary Prognosis of Ventricular Septal Rupture Complicating Acute Myocardial Infarction: A Single-Center Experience.

Objectives: Ventricular septal rupture (VSR) is a rare but lethal complication of acute myocardial infarction (AMI). We conducted a retrospective analysis of the clinical characteristics of VSR patients and explored the risk factors for long-term mortality. Methods: In this single-center cohort study, 127 patients diagnosed with post-AMI VSR between May 2012 and April 2019 were included. Demographic, clinical, operative, and outcome data were collected. The 30-day and long-term mortality were outcomes of interest. Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The mean age of the VSR cohort was 66.6 ± 8.7 years, 67 (52.8%) were males. Among the 127 patients, 78 patients (61.4%) were medically managed, 31 (24.4%) patients underwent percutaneous transcatheter closure (TCC), and 18 (14.2%) patients received surgical repair. The median follow-up time was 1129 days [interquartile range: 802-2019 days]. The 30-day mortality of the medically managed group, percutaneous TCC group, and surgical management group was 93.6, 22.6, and 11.1%, respectively; and the long-term mortality was 96.2, 25.8, and 22.2%, respectively. VSR repair treatment including surgical management (HR 0.01, 95% CI 0.001-0.09, p < 0.001) and percutaneous TCC (HR 0.09, 95% CI 0.03-0.26, p < 0.001) was associated with a better prognosis, and cardiogenic shock (CS) (HR 9.30, 95% CI 3.38-25.62, p < 0.001) was an independent risk factor of long-term mortality. Conclusions: The prognosis of VSR patients without operative management remains poor, especially in those complicated with CS. Timely and improved surgery treatment is needed for better outcomes in VSR patients.

Precise diagnosis of three top cancers using dbGaP data.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating p53 and RAP2A in vitro and in vivo.

PURPOSE: Patients with type 1 diabetes (T1D) are associated with a high risk of multiple complications, so the development of T1D treatment is urgently needed. This study was set out to explore the molecular mechanism of metformin in the treatment of T1D insulin resistance. PATIENTS AND METHODS: Subcutaneous adipose tissues were collected from 68 T1D patients and 51 healthy controls. Insulin resistance model rats and cells were constructed and treated with metformin respectively. Western blot was used to detect p53 and RAP2A protein levels, and qPCR was utilized to measure p53 and RAP2A mRNA levels. SiRNA and RAP2A siRNA vectors were constructed to observe their effects on insulin resistance model cells. RESULTS: In T1D, p53 was up-regulated, while RAP2A was down-regulated. Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A. P53 induced insulin resistance and inflammatory response by inhibiting RAP2A and promoted apoptosis. CONCLUSION: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.

Panax Notoginseng Saponins Protect Cardiac Myocytes Against Endoplasmic Reticulum Stress and Associated Apoptosis Through Mediation of Intracellular Calcium Homeostasis.

Endoplasmic reticulum (ER) stress has been demonstrated to play important roles in the pathogenesis of various cardiovascular diseases. The ER stress pathway is therefore a promising therapeutic target in cardiovascular disease. Although Panax notoginseng saponins (PNS) are one of the patent medicines that are traditionally used to treat cardiovascular disorders, their effects on ER stress in cardiac myocytes remain unexploited so far. This study investigates the effects of PNS on ER stress and its associated cell apoptosis along with the related mechanism in cardiac myocytes. PNS compounds were identified via high-performance liquid chromatograph (HPLC) assay. PNS-pretreated H9c2 cells, HL-1 cells, and primary cultured neonatal rat cardiomyocytes were stimulated with thapsigargin (TG) to induce ER stress response and apoptosis. ER stress response was tested by immunofluorescence or immunoblot of the ER protein chaperones-calnexin, binding immunoglobulin protein (BiP) and the C/EBP homologous protein (CHOP). Cell viability was tested by methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis was detected by immunoblot of Cleaved caspase-3 and flow cytometry analysis of Annexin V/propidium iodide (PI) staining. Cytosolic, mitochondrial, and ER calcium dynamics were investigated by calcium imaging. Moreover, a ryanodine receptor type-2 (RyR2) overexpression stable cell line was generated to verify the mechanism of RyR2 involved in PNS in the inhibition of ER stress and cell apoptosis. We demonstrate here that PNS protected cardiac myocytes from ER stress response and associated cell death in a concentration-dependent manner. Importantly, PNS reduced the elevation of cytosolic calcium, mitochondria calcium, as well as ER calcium in response to either TG or histamine treatment. PNS protection in ER stress was regulated by RyR2 expression. In summary, PNS protection against TG-induced ER stress response and its associated cell apoptosis in cardiac myocytes is calcium dependent. Through the regulation of ER calcium release mediated by RyR2, a novel mechanism for PNS in the prevention of cardiovascular diseases is thereby identified.

[Clinical features of imported schistosomiasis mansoni in Beijing City：a report of 6 cases].

OBJECTIVE: To analyze the clinical features of 6 patients with imported schistosomiasis mansoni, including the epidemic history, clinical manifestations, laboratory tests and therapeutic effect, so as to provide references for improving the levels of diagnosis and treatment of physicians. METHODS: The clinical data of 6 patients with imported schistosomiasis mansoni from January 2009 to July 2016 were collected and analyzed. RESULTS: All the 6 imported patients with schistosomiasis mansoni had a clear history of cercarial infested water exposure. The main manifestations were continuous fever and eosinophilia. Three (50%) patients were accompanied with diarrhea. Anti-Schistosoma japonicum IgG antibody were cross positive in 2 (33.3%) patients, while live eggs of S. mansoni were explored in intestinal mucosa specimens of all the patients. CD3+CD8+ T cell ratio was decreased significantly but B cell ratio was elevated in all the patients, and the main immunoglobulin of the patients was IgG. Hydroperitoneum and splenomegaly signs were discovered by abdominal ultrasonography in 16.6% (1/6) of the patients. Multiple liver nodules and wall thickening of rectum and sigmoid colon were revealed by pelvic MR scan in 16.6% (1/6) of the patients. Colitis was found in all the patients, and 66.6% (4/6) of the patients were combined with multiple colonic ulcers by the electronic colonoscopy examination. Chronic inflammation and eosinophil infiltration were found in all the patients by rectum pathology. All 6 patients were cured with chemotherapy named praziquantel. CONCLUSIONS: Comprehensive analysis of clinical data including epidemiological history, specific manifestations, laboratory tests and intestinal mucosa pathology may be benefit of the management of schistosomiasis mansoni.

IRE1α deficiency impairs autophagy in chondrocytes by upregulating calcium homeostasis endoplasmic reticulum protein / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.

LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma.

OBJECTIVE: To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1) in human osteosarcoma cells. METHODS: Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. RESULTS: Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1, since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. CONCLUSION: Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

Screening results and genetic features of glucose-6-phosphate dehydrogenase deficiency in 54 025 preterm infants in Chengdu, China / 中国当代儿科杂志

OBJECTIVE@#To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants.@*METHODS@#Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results.@*RESULTS@#Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age T mutation tend to have mild conditions.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients / 中国医学科学杂志(英文版)

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (

In vivo and in vitro inductively coupled plasma mass spectrometry quantification of minerals and heavy metals in Qishiwei Zhenzhu pill and their effect on intestinal flora / 中国药理学与毒理学杂志

OBJECTIVE Cerebral ischemia or ischemic stroke is due to insufficient blood supply to the brain, which causes hypoxia or ischemia in some areas. This work aimed to quantify the minerals and heavy metals in Qishiwei Zhenzhu pill in vivo and in vitro, analyze its effect on the types and abundance of intestinal flora, and study its mechanism on inflammation and apoptosis pathways as a treatment for cerebral ischemia. METHODS Microwave digestion and induc?tively coupled plasma mass spectrometry (ICP-MS) were used to determine the minerals and heavy metals in 10 batches of Qishiwei Zhenzhu pill in vitro. With the use of the middle cerebral artery obstruction (MCAO) model, ICP-MS was applied to determine the content of minerals and heavy metals in hepatic portal vein blood, abdominal aortic blood, brain, liver, kidney, hair, urine and feces at different time periods. On this model, the ileum, cecum, and colon tissues were tested for intestinal pathology, and 16S rRNA was used for sequencing. Species taxonomy, α diversity, and spe?cies microbial composition and structure analysis were also performed. Polymerase chain reaction and Western blotting were employed to determine the mRNA and protein expression of p38 MAPK, caspase-3, IL-1β and TNF-α in the isch?emic brain tissues of rats. RESULTS The average content of heavy metals in the 10 batches of Qishiwei Zhenzhu pill samples is in the descending order Hg>Cu>Pb. Significant differences in the metal elements are found among Qishiwei Zhenzhu pill from different manufacturers but not among the different batches of the same manufacturer. An extremely low content of heavy metals are absorbed into the blood or accumulated in the brain, liver, kidney, and other tissues. Stool is the main excretion route of minerals and heavy metals from Qishiwei Zhenzhu pill. This medicine helps repair the intestinal mucosa in MCAO rats. At the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the intestinal flora of rats with cerebral ischemia. At the genus level, it can adjust the abundance of Escherichia Shigella. At the species level, it can adjust the abundance of Lactobacillus yoelii and Lactobacillus reuteri. Cluster classification results show that Qishiwei Zhenzhu pill can improve the intestinal flora of rats with cerebral ischemia, reduce the mRNA and protein expression of caspase-3 and IL-1βin rat brain tissues, and have a tendency to decrease the mRNA expres?sion of p38 MAPK and TNF-α. CONCLUSION Quantifying the minerals and heavy metals in Qishiwei Zhenzhu pill in vivo and in vitro will help improve their quality standards. Minerals and heavy metals are mainly excreted in feces, accumu?late in extremely low levels in various tissues, and do not damage the intestinal mucosa. The effective material basis of Qishiwei Zhenzhu pill in treating cerebral ischemia may be related to their Li, Cr, and Cd elements. These pills can improve the environment of intestinal flora, and their mechanism of treatment for cerebral ischemia may be related to the down-regulation of IL-1βinflammatory factor and inhibition of cell apoptosis.

Applicative Value of Serum CA19-9, CEA, CA125 and CA242 in Diagnosis and Prognosis for Patients with Pancreatic Cancer Treated by Concurrent Chemoradiotherapy.

OBJECTIVE: To evaluate the application value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis of pancreatic cancer cases treated with concurrent chemotherapy. MATERIALS AND METHODS: 52 patients with pancreatic cancer, 40 with benign pancreatic diseases and 40 healthy people were selected. The electrochemiluminescence immunoassay method was used for detecting levels of CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for assessing the level of CA242. The Kaplan-Meier method was used for analyzing the prognostic factors of patients with pancreatic cancer. The Cox proportional hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential interval (CI) for survival time of patients with pancreatic cancer. RESULTS: The levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic diseases and healthy people (P<0.001). The sensitivity of CA19-9 was the highest among these, followed by CA242, CA125 and CEA. The specificity of CA242 is the highest, followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously higher than single detection of those markers in diagnosis of pancreatic cancer. The median survival time of 52 patients with pancreatic cancer was 10 months (95% CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125, CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression analysis showed that CA19-9 was an independent prognostic factor for patients with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). CONCLUSIONS: The detection of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer and joint detection of tumor markers helps improve the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor for patients with pancreatic cancer.

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia / 中国医学科学杂志(英文版)

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 μmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 μmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Study on fingerprint of Aucklandiae Radix based on principal component analysis coupled with cluster analysis / 中草药

Objective: To establish a UPLC fingerprint method and a method for the content determination of 3,5-O-dicaffeoylquinic acid of Aucklandiae Radix, and provide a comprehensive evaluation of the drug from different habitats. Methods: UPLC analysis was performed on a YMC Trait C18 (100 mm × 2.1 mm, 1.9 μm), with a mobile phase consisting of acetonitrile-0.05% phosphoric acid at the flow rate of 0.30 mL/min. The fingerprint detection wavelength was 254 nm and the content determination detection wavelength of 3,5-O-dicaffeoylquinic acid was 327 nm, meanwhile, the column temperature was controlled at 30 ℃. Similarity analysis, hierarchical clustering analysis, and principal component analysis were undertaken to investigate the fingerprints of 13 batches of Aucklandiae Radix. Results: UPLC fingerprint of Aucklandiae Radix was established and eight common peaks were designated. The results showed that the quality of the batches of samples were not stable. Samples collected from the same region and different regions both had certain differences, as well as the content determination of 3,5-O-dicaffeoylquinic acid. Conclusion: The proposed method offered a fast, holistic, and effective method for the quality control of Aucklandiae Radix.

Chemical constituents of Euphorbia tibetica and their biological activities.

AIM: To investigate the chemical constituents and their biological activities of the aerial parts of Euphorbia tibetica. METHOD: Compounds were isolated and purified by various chromatographic methods, and their structures were elucidated through the use of extensive spectroscopic techniques including 2D-NMR, the structures of compounds 5 and 6 were confirmed by single-crystal X-ray crystallography. Bioactivities of all the isolated compounds were evaluated by the MTT method on A549 and anti-angiogenesis assay. RESULTS: One new compound, methyl 4-epi-shikimate-3-O-gallate (1), together with twenty-three known constituents (2-24) were isolated from the aerial parts of E. tibetica. CONCLUSION: Compound 1 is new, and the other compounds were isolated from this plant for the first time. Compounds 5-7, 9, 11, 17, 18 and 20 exhibited inhibitory effects on the growth of human lung cancer cell A549 and compounds 5, 7, 12, 13, 17 and 19 showed anti-angiogenic effects in a zebrafish model.