Palladium-catalyzed asymmetric carbene coupling en route to inherently chiral heptagon-containing polyarenes.

Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross-coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.

Eco-Friendly Fabrication of Highly Stable Silica Aerogel Microspheres with Core-Shell Structure.

Silica aerogel microspheres show great potential in various fields as fillings in different materials. It is important to diversify and optimize the fabrication methodology for silica aerogel microspheres (SAMS). This paper presents an eco-friendly synthetic technique for producing functional silica aerogel microspheres with a core-shell structure. Mixing silica sol with commercial silicone oil containing olefin polydimethylsiloxane (PDMS) resulted in a homogeneous emulsion with silica sol droplets dispersed in the oil. After gelation, the droplets were transformed into silica hydrogel or alcogel microspheres and coated with the polymerization of the olefin groups. Microspheres with silica aerogel as their core and polydimethylsiloxane as their shell were obtained after separation and drying. The sphere size distribution was regulated by controlling the emulsion process. The surface hydrophobicity was enhanced by grafting methyl groups onto the shell. The obtained silica aerogel microspheres have low thermal conductivity, high hydrophobicity, and excellent stability. The synthetic technique reported here is expected to be beneficial for the development of highly robust silica aerogel material.

Pruney Finger-Inspired Switchable Surface with Water-Actuated Dynamic Textures.

Switchable surfaces play an important role in the development of functional materials. However, the construction of dynamic surface textures remains challenging due to the complicated structural design and surface patterning. Herein, a pruney finger-inspired switchable surface (PFISS) is developed by constructing water-sensitive surface textures on a polydimethylsiloxane substrate by taking advantage of the hygroscopicity of the inorganic salt filler and the 3D printing technology. Like human fingertips, the PFISS shows high water sensitivity with obvious surface variation in wet and dry states, which is actuated by water absorption-desorption of the hydrotropic inorganic salt filler. Besides, when the fluorescent dye is optionally added into the matrix of the surface texture, water-responsive fluorescent emitting is observed, providing a feasible surface-tracing strategy. The PFISS shows effective regulation of the surface friction and performs a good antislip effect. The reported synthetic strategy for the PFISS offers a facile way for building a wide range of switchable surfaces.

Efficacy and Safety of Coronary Intervention via Distal Transradial Access (dTRA) in Patients with Low Body Mass Index.

The study aimed to investigate the efficacy and safety of coronary intervention via distal transradial access (dTRA) in patients with low body mass index (BMI). A total of 67 patients with low BMI who underwent coronary intervention, comprising 29 patients via dTRA and 38 patients via conventional transradial access (cTRA), were retrospectively included. There was no significant difference in the puncture success rate between the two groups (dTRA 96.6%, cTRA 97.4%, P=0.846). Compared with the cTRA group, the success rate of one-needle puncture in the dTRA group was lower (51.7% vs. 81.6%, P=0.020). The compression haemostasis time in the dTRA group was shorter than that in the cTRA group (P < 0.001). However, the incidence of radial artery occlusion was lower in the dTRA group than in the cTRA group (4.0% vs. 33.3%, P=0.007). In conclusion, coronary intervention via dTRA was safe and effective in patients with low BMI.

Circular RNA circ_0006089 promotes the progression of gastric cancer by regulating the miR-143-3p/PTBP3 axis and PI3K/AKT signaling pathway.

OBJECTIVES: Circular RNAs (circRNAs) play pivotal roles in malignancies including gastric cancer (GC). We aimed to investigate the biological function and regulatory mechanism of circ_0006089 in GC. METHODS: Circ_0006089, microRNA (miR)-143-3p, and polypyrimidine tract-binding protein 3 (PTBP3) expressions were measured via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in GC cell lines. Cell proliferative capacity was determined by colony formation and CCK-8 assays. Flow cytometry was employed for measuring cell apoptosis. Cell invasion and migration were measured via transwell and wound-healing assays. Western blot analysis was utilized for detecting protein expressions of E-cadherin, N-cadherin, vimentin, PTBP3, PI3K, p-PI3K, AKT, and p-AKT. Dual-reporter luciferase analysis was conducted to confirm the association between miR-143-3p and circ_0006089 or PTBP3. The role of circ_0006089 in vivo was detected via establishing a mice xenograft model. RESULTS: Circ_0006089 expression was increased in GC. Circ_0006089 downregulation suppressed the proliferation and metastasis and induced apoptosis of GC cells, which was counteracted by miR-143-3p inhibition or PTBP3 overexpression. In addition, circ_0006089 overexpression could promote GC progression. MiR-143-3p specially bound to circ_0006089 and PTBP3 was targeted by miR-143-3p. Moreover, circ_0006089 could regulate PTBP3 expression and the PI3K/AKT pathway by sponging miR-143-3p. Circ_0006089 knockdown also suppressed tumor growth. CONCLUSION: Circ_0006089 regulated miR-143-3p/PTBP3/PI3K/AKT pathway to facilitate GC progression.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Safety and efficacy of coronary angiography and percutaneous coronary intervention via distal transradial artery access in the anatomical snuffbox: a single-centre prospective cohort study using a propensity score method.

BACKGROUND: This study investigated the safety and efficacy of coronary angiography (CAG) and percutaneous coronary intervention (PCI) via distal transradial artery access (d-TRA). METHODS: For this single-centre prospective cohort study, a total of 1066 patients who underwent CAG or PCI procedures from September 2019 to November 2020 were included. Patients were divided into two groups: the d-TRA group (346) and the conventional transradial artery access (c-TRA) group (720) based on access site. A total of 342 pairs of patients were successfully matched using propensity score matching (PSM) for subsequent analysis. RESULTS: No significant differences in puncture success rate, procedural method, procedural time, sheath size, contrast dosage or fluoroscopy time were noted between the two groups. The puncture time in the d-TRA group was longer than that in the c-TRA group (P < 0.01), and the procedure success rate was lower than that in the c-TRA group (90.94% vs. 96.49%, P = 0.01). The haemostasis time in the d-TRA group was shorter than that in the c-TRA group (P < 0.01), and the visual analogue scale (VAS) was lower than that in the c-TRA group (P < 0.01). In addition, the prevalence of bleeding and haematoma in the d-TRA group was lower than that in the c-TRA group (1.75% vs. 7.31%, P < 0.01; 0.58% vs. 3.22%, P = 0.01, respectively). No significant difference in the incidence of numbness was noted between the two groups. No other complications were found in two groups. CONCLUSION: d-TRA is as safe and effective as c-TRA for CAG and PCI. It has the advantages of improved comfort and fewer complications. Trail registration Chinese Clinical Trial Registry, ChiCTR1900026519.

Recanalization of the occluded radial artery via distal transradial access in the anatomic snuffbox.

BACKGROUND: Radial artery occlusion is a common complication after coronary angiography and percutaneous coronary intervention via the transradial access. In recent years, coronary angiography and percutaneous coronary intervention via the distal transradial access has gradually emerged, but recanalization of the occluded radial artery through the distal transradial access has rarely been reported. CASE PRESENTATION: A 67-year-old female with arterial hypertension and diabetes mellitus was admitted to the hospital due to chest pain for three hours. She was diagnosed with acute myocardial infarction. After admission, the patient successfully underwent emergency coronary angiography and percutaneous coronary intervention through the right transradial access. Radial artery occlusion was found after the operation, and recanalization was successfully performed through the right distal transradial access before discharge. Immediately after the operation and one month later, vascular ultrasonography showed that the antegrade flow was normal. CONCLUSIONS: This report presents a case of radial artery occlusion after emergency coronary angiography and percutaneous coronary intervention in which recanalization was successfully performed through the right distal transradial access. This case demonstrates that recanalization of a radial artery occlusion via the distal transradial access is safe and feasible.

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes.

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

Huaier Granule Combined with Tegafur Gimeracil Oteracil Potassium Promotes Stage IIb Gastric Cancer Prognosis and Induces Gastric Cancer Cell Apoptosis by Regulating Livin.

Gastric cancer is one of the most common malignancies worldwide, with high morbidity and poor survival rate. Its prognosis remains unsatisfactory, with a 5-year survival rate of <30%. Studies have indicated that Huaier granules have good antitumor efficacy and safety in several solid malignant tumors. Recent studies have also found that Huaier polysaccharides can promote apoptosis in numerous tumor cells, although only few studies have focused on the effects of Huaier granules on gastric cancers and the mechanisms underlying their antitumor role. We retrospectively evaluated stage IIb gastric cancer patients at Xiangya Hospital, Central South University, through our outpatient system from January 2013 to December 2015. Fifty-four patients were in the Huaier+Tegafur Gimeracil Oteracil Potassium (TGOP) group and 72 in the TGOP group. Further, we conducted CCK8, colony formation, Annexin V-FITC/PI, Western blot, RT-PCR, and plasmid transfection assays to analyze the mechanism by which Huaier polysaccharides play an antitumor role. We confirmed that Huaier granules combined with Tegafur Gimeracil Oteracil Potassium could promote patient prognosis, with a better disease-free survival rate (51.32 ± 2.23 vs. 44.19 ± 2.26, p = 0.034) and overall survival rate (56.81 ± 1.32 vs. 51.32 ± 1.69, p = 0.020). Moreover, through cell proliferation assays, Western blot, RT-PCR, and detection of Livin expression at the mRNA and protein levels, we found that Huaier polysaccharides could promote gastric cancer cell apoptosis and inhibit gastric cancer cell proliferation in a time- and dose-dependent manner. Finally, we demonstrated that Huaier polysaccharides promote gastric cancer cell apoptosis through the regulation of Livin expression. Overexpression of Livin reversed the gastric cell apoptosis induced by Huaier polysaccharides. Huaier granules combined with Tegafur Gimeracil Oteracil Potassium ameliorated stage IIb gastric cancer prognosis and induced gastric cancer cell apoptosis by regulating Livin.

Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study.

BACKGROUND: Preoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs. METHODS: We retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded. RESULTS: A total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%. CONCLUSION: Preoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.

Association between CTLA-4 gene polymorphism and myasthenia gravis in a Chinese cohort.

Abnormal CTLA-4 expression is involved in the development of myasthenia gravis (MG), and serum CTLA-4 levels are positively correlated with serum anti-AChR antibody concentration, which might be related with the severity of MG. Polymorphism in CTLA-4 gene is associated with various autoimmune disorders. We investigated the association of polymorphism in CTLA-4 gene with the clinical variables and severity of MG. The frequencies of alleles and genotypes were compared between 480 MG patients and 487 healthy controls, as well as among subgroups of MG patients. The frequency of rs733618*C allele is significantly higher in MG group and several subgroups than in control group. Genotype is not found as independent factor for essential clinical variables of MG. The frequency of rs231775*A allele is significantly lower in ocular onset subgroup than in control group, and the frequencies of rs231775*A allele and rs3087243*A allele are significantly lower in ocular onset subgroup than in generalized onset subgroup. Genotypes of the two SNPs are found as independent factors for ocular onset. The frequency of rs231775*A allele is significantly lower in mild subgroup than that in control group. Genotype is not found as independent factor for mild severity. A haplotype containing rs733618*C, rs231775*G and rs3087243*G is identified to increase the general risk of MG by 1.278-fold and ocular onset MG subgroup by 1.362-fold. There is association of rs733618 with the general susceptibility of MG, and association of rs231775 and rs3087243 with the susceptibility of ocular onset MG, but no association with the severity of MG.

Factors Correlating to the Development of Hepatitis C Virus Infection among Drug Users-Findings from a Systematic Review and Meta-Analysis.

Hepatitis C remains a significant public health threat. However, the main routes of transmission have changed since the early 1990s. Currently, drug use is the main source of hepatitis C virus (HCV) infection, and some measures have been successively implemented and additional studies have been published. However, the factors correlating with HCV infection failed to clearly define. Our study pooled the odds ratios (ORs) with 95% confidence intervals (CIs) and analyzed sensitivity by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Publication bias was determined by Egger's test. In our meta-analysis, HCV-infected and non-HCV-infected patients from 49 studies were analyzed. The pooled ORs with 95% CIs for study factors were as follows: Injecting drug use 10.11 (8.54, 11.97); sharing needles and syringes 2.24 (1.78, 2.83); duration of drug use >5 years 2.39 (1.54, 3.71); unemployment 1.50 (1.22, 1.85); commercial sexual behavior 1.00 (0.73, 1.38); married or cohabiting with a regular partner 0.88 (0.79, 0.98), and sexual behavior without a condom 1.72 (1.07, 2.78). This study found that drug users with histories of injecting drug use, sharing needles and syringes, drug use duration of >5 years, and unemployment, were at increased risk of HCV infection. Our findings indicate that sterile needles and syringes should be made available to ensure safe injection. In view of that, methadone maintenance treatment can reduce or put an end to risky drug-use behaviors, and should be scaled up further, thereby reducing HCV infection.

Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double-strand breaks.

TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation. Mechanically, overexpression of TNKS1BP1 increased the accumulation of S phase cells, which was accompanied by a decrease in M phase cells. More importantly, we found TNKS1BP1 regulated genome stability, mainly through affecting the homologous recombination pathway of DNA double-strand breaks by inhibiting the RAD51 foci formation. Overall, our study indicates that, in LAC, aberrant expressions of TNKS1BP1 are common events, and overexpression of TNKS1BP1 might affect outcomes of cancer patients to chemotherapy and radiotherapy.

Proliferation and Apoptosis of Leukemia Cell Line K562 Treated with HSP90 Inhibitor 17-DMAG / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of HSP90 in proliferation and apoptosis of leukemia cells K562 through detecting the effect of HSP90 inhibitors 17-[2-(Dimethylamino) ethyl] amino-17-desmethoxygeldanamycin(17-DMAG) on leukemia K562 cell lines.</p><p><b>METHODS</b>The K562 cells were treated with HSP90 inhibitors 17-DMAG, the semi-quantitative PCR was used to detect HSP90 gene expression, the WST was used to detect the effect 17-DMAG on cell proliferation as well as Annexin V flow cytometry was used to detect the cell apoptosis.</p><p><b>RESULTS</b>After 17-DMAG treated the K562 cells in different stage, the K562 cell growth was obviously inhibited with time dependent (48 h)(r=0.9918) and dose dependent(3.2 µmol/L) manners (r=0.9999) (P<0.01); after the K562 cells in different stage were treated with different concentrations of 17-DMAG, the K562 cells showed significant apoptosis and with dosage-dependent mauner (r=0.9903)(P<0.01); HSP90 mRNA expression decreased significantly after K562 cells were treated with different concentrations of 17-DMAG for 48 hours. 17-DAMG down-regulated the HSP90 mRNA expression in dosage-dependent mauner as well(r=0.9227) (P<0.01).</p><p><b>CONCLUSION</b>HSP90 inhibitor 17-DMAG can inhibit the proliferation of K562 cells and induce their apoptosis. This study result provides laboratory basis for the treatment of leukemia patients with 17-DMAG.</p>

Effect of Heat Shock Protein 90 Inhibitor 17-DMAG on Proliferation and Apoptosis of Acute Lymphocytic Leukemia Cell Line Jurkat / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of heat shock protein 90(HSP90) inhibitor 17-DMAG, an inhibitor specific for heat shock protein 90, on the proliferation and apoptosis of acute lymphocytic leukemia cell lines Jurkat.</p><p><b>METHODS</b>Jurkat cells were collected, then were treated with 17-DMAG. The expression of HSP90 was examined by semi-quantitative RT-PCR analysis, the effect of 17-DMAG on cell proliferation were detected by using WST, and cell apoptosis were detected by using flow cytometry with Annexin V/PI double stenining.</p><p><b>RESULTS</b>After Jurkat cells were treated with different concentrations of 17-DMAG for 48 hours, the HSP90 mRNA expression decreased significantly in dose dependent manner (r=0.9530, P<0.01). The ICwas 3.17 mmol/L when the Jurkat cells were treated with 17-DMAG for 48 h; after treating Jurkat cell with 17-DMAG, the cell proliferation was inhibited(r=0.9903, P< 0.01), the cell apoptosis was increased in dose dependent manner (r=0.9876, P<0.01).</p><p><b>CONCLUSION</b>17-DMAG can inhibit the Jurkat cell proliferation and induce the Jurkat cell apoptosis.</p>

Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease / 法医学杂志

Objective To study the expression change of pro-brain natriuretic peptide (proBNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in sudden death of coronary atherosclerotic heart disease,and to explore its application in forensic diagnosis.Methods Myocardial and blood samples were collected from normal control group,sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group (20 cases in each group).The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting,and that of BNP mRNA were detected by reverse transcription PCR (RT-PCR).The content of NT-proBNP in plasma were detected by ELISA.Results Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group.There was no positive expression in normal control group.For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group,the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group (P＜0.05).The NT-proBNP content in plasma of sudden death of coronary atherosclerotic heart disease group was higher than that of single coronary stenosis group (P＜0.05).Conclusion In myocardial ischemia condition,the higher expression of proBNP in cardiac muscle cell shows that the detection of NT-proBNP in plasma can be useful to differentially diagnose the degree of coronary atherosclerotic heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease.

Protocol of a prospective study for the combination treatment of Shu-Gan-jian-Pi decoction and steroid standard therapy in autoimmune hepatitis patients.

BACKGROUND: Prednisone plus azathioprine is considered the mainstay of therapy in the current recommendations for autoimmune hepatitis (AIH). However, it does not provide good benefits for AIH patients because of its serious side effects. Therefore, more and more AIH patients prefer to seek for traditional Chinese medicine (TCM) to manage their symptoms and reduce the side effects of steroids in China. Shu-Gan-Jian-Pi Decoction is a popular used Chinese herbal formula in Guangdong province of China, which has demonstrated the effect of improving efficacy and reducing side effects of corticosteroids in AIH patients. The aim of this study is to evaluate the effects of Shu-Gan-Jian-Pi Decoction combined with steroid in AIH patients. So, this study aims to explore whether the combination treatment of Shu-Gan-Jian-Pi Decoction and steroid standard therapy could improve the clinical management of AIH. METHODS: A prospective non-randomized study on AIH will be conducted between October 2015 and June 2017 in Guangdong Provincial hospital of Chinese medicine. Eligible AIH patients will be classified as the case group (n = 66) and the control group (n = 66) based on the interventions. Patients taking Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine will be in the case group and those taking prednisone and azathioprine will be in the control group. The whole study will last 48 weeks, including a 24-week observation period and a 24-week follow-up period. The primary outcome was complete response to therapy, defined as complete biochemical remission at the patient's last visit of observation period and the absence of predefined steroid-specific side effects throughout treatment. DISCUSSION: This trial will evaluate the efficacy and safety of Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine on AIH patients. The achievement of this trial will provide evidence-based data for Shu-Gan-Jian-Pi Decoction, which could provide good benefits for AIH patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OOC-15006155 . Registration date: 28 March 2015.

Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population.

Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the genetic variants might be used as molecular markers for evaluating the risk of T2DM and diabetic nephropathy. © 2016 IUBMB Life, 68(7):516-525, 2016.