Associations of elevated glucose levels at each time point during OGTT with fetal congenital heart diseases: a cohort study of 72,236 births.

BACKGROUND: It remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring. METHODS: We conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD. RESULTS: A total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses. CONCLUSION: Elevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD.

Astramalabaricosides A-T, Highly Oxygenated Malabaricane Triterpenoids with Migratory Inhibitory Activity from Astragalus membranaceus var. mongholicus.

Twenty new malabaricane triterpenoids, astramalabaricosides A-T (1-20), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1-20 were characterized as glycosides with a highly oxygenated side chain, and 13-20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1-20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.

Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy.

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P1, are fungi-derived antimicrobials with little cross-resistance to commonly used antibiotics. Generation of new fusidane-type derivatives is therefore of great value, but this is hindered by available approaches. Here, we developed a stochastic combinational strategy by random assembly of all the post-tailoring genes derived from helvolic acid, fusidic acid, and cephalosporin P1 biosynthetic pathways in a strain that produces their common intermediate. Among a total of 27 gene combinations, 24 combinations produce expected products and afford 58 fusidane-type analogues, of which 54 are new compounds. Moreover, random gene combination can induce unexpected activity of some post-tailoring enzymes, leading to a further increase in chemical diversity. These newly generated derivatives provide new insights into the structure‒activity relationship of fusidane-type antibiotics. The stochastic combinational strategy established in this study proves to be a powerful approach for expanding structural diversity of natural products.

Benzannulated 5,5-spiroketal sesquiterpenes from the roots of Angelica Pubescens.

Two new tetrahydrobenzannulated 5,5-spiroketal sesquiterpenes (1 and 2) and three novel benzannulated 5,5-spiroketal sesquiterpenes (3-5) namely angepubesins A-E, together with a new heliannane-type benzannulated sesquiterpene namely angepubesin F (6) and two known monoterpenes (7 and 8), were isolated from the roots of Angelica Pubescens. Their structures were identified by various spectroscopic analyses (NMR, MS, UV, IR), in combination with 13C NMR calculation as well as MAE, CMAE, DP4 + and MAEΔΔδ values analyses. The absolute configurations of 1-6 were determined by modified Mosher's method, ECD calculation and single-crystal X-ray diffraction (Cu Kα). Furthermore, the inhibitory activities of these isolated compounds against nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells were evaluated. The results showed that compounds 2-4, 6 and 7, especially 6, displayed markedly inhibitory effects on NO production in a concentration-dependent manner. Mechanical study revealed that compound 6 could significantly inhibit the expression of nitric oxide synthase (iNOS) protein at a concentration of 10 µM. In addition, compound 6 suppressed the activation of JAK-STAT and NF-κB pathways.

The Oxidation Cascade of a Rare Multifunctional P450 Enzyme Involved in Asperterpenoid A Biosynthesis.

The cytochrome P450 enzymes (P450s or CYPs) are heme-containing enzymes which catalyze a wide range of oxidation reactions in nature. In our previous study, a rare multifunctional P450 AstB was found, which can dually oxidize two methyl groups (C-19 and C-21) of preasperterpenoid A to asperterpenoid A with 3-carboxyl and 11-hydroxymethyl groups. However, the oxidation order of C-19 and C-21 catalyzed by AstB is unclear. In order to reveal this oxidation order, probable pathways catalyzed by AstB were proposed, and the oxidation order of C-19 and C-21 was obtained by quantum chemistry calculations. The potential intermediates (three new asperterpenoids D-F, 1-3) were obtained through the chemical investigation on the extract of the transformant strain and chemical conversions, which were used as the standards to detect their existences in the extract of the transformant strain with HPLC-MS. Combined with the quantum chemistry calculation and the HPLC-MS analysis, the catalyzed order of AstB in asperterpenoid A biosynthesis was revealed. Furthermore, the mPTPB inhibition of obtained asperterpenoids was evaluated, and the results showed that 3-carboxyl and the oxidation station of C-21 would be the key factors for mPTPB inhibition of asperterpenoids.

4-Hydroxy Pyridones from Heterologous Expression and Cultivation of the Native Host.

4-Hydroxy pyridones are a class of fungi-derived polyketide-nonribosomal peptide products featuring a core of 4-hydroxy-2-pyridone which have a wide range of biological activities. Genome mining of in-house strains using polyketide synthase-nonribosomal peptide synthase as a query identified an endophyte Tolypocladium sp. 49Y, which possesses a potential 4-hydroxy pyridone biosynthetic gene cluster. Heterologous expression in Aspergillus oryzae NSAR1 revealed that this gene cluster is functional and able to produce a rare type of 4-hydroxy pyridones called tolypyridones (compounds 3 and 4). Tolypocladium sp. 49Y was grown in a variety of media which led to the isolation of six 4-hydroxy pyridones (5-10) and one pyrrolidone (11) from a rice culture, and compounds 3 and 9 showed antifungal activity. These latter compounds are different from those obtained by heterologous expression. This study shows that both heterologous expression and cultivation of the native host are complementary approaches to discover new natural products.

Preoperative Low-dose and High-dose Pregabalin and Cardiovascular Response to Endotracheal Intubation: A Prospective, Randomized, Single-blind, Controlled Study in China.

PURPOSE: A prospective, randomized, single-blind, controlled clinical study was designed to evaluate the efficacy and tolerability of preoperative pregabalin on cardiovascular response to laryngoscopy and endotracheal intubation. METHODS: Patients aged 18-60 years with an American Society of Anesthesiologists scale score of I or II were recruited and randomly allocated to receive placebo (control), low-dose (150-mg) pregabalin, or high-dose (300-mg) pregabalin. The medications were orally administered 1 hour before general anesthesia. Heart rate, systolic and diastolic blood pressures, and mean arterial blood pressure were measured and recorded prior to the administration of placebo or pregabalin; before endotracheal intubation; and at 0, 1, 3, 5, 7, and 10 minutes after intubation. The sedation score was evaluated 1 hour after the administration of placebo or pregabalin. FINDINGS: A total of 90 patients were enrolled (n = 30 per group). Pregabalin (150 or 300 mg) was associated with reduced blood pressure fluctuations after intubation, but with no significant differences between the 2 dose groups. Pregabalin was associated with an inhibitory effect on heart rate fluctuations and reduced hemodynamic complications after intubation, in a dose-dependent manner, but no effect on the required perioperative opioid dosage was found. Both doses were effective in reducing preoperative anxiety, but visual analog scale pain scores at 1 hour after surgery were reduced only in limb and spine as well as abdominal surgeries. A pregabalin-related adverse reaction was dizziness, which was observed at 1 hour after surgery in both groups. IMPLICATIONS: In this study, high-dose (300-mg) pregabalin effectively attenuated cardiovascular response after endotracheal intubation. ClinicalTrials.gov identifier: NCT03456947.

The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma.

OBJECTIVE: The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). METHODS: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. RESULTS: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). CONCLUSION: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR-1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC.

Increased serum resistin levels correlate with psoriasis: a meta-analysis.

BACKGROUND: Recent studies implicate adipokines in the pathogenesis of inflammatory diseases, including psoriasis. In this study we evaluated the significance of serum resistin levels in psoriasis patients using a meta-analysis approach.223 METHODS: Relevant articles were retrieved by searching the following English and Chinese databases: Cochrane Library, PubMed, Springer Link, Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI). The retrieved studies were subjected to a thorough screening procedure to identify case-control studies that contained the required data. Data was extracted from each study and Version 12.0 STATA statistical software was employed for statistical analyses. RESULTS: Nine case-control studies, containing 421 psoriasis patients and 348 healthy controls, were included in this study. The major result of the meta-analysis revealed a statistically significant association between serum resistin levels and psoriasis (SMD=2.22, 95%CI: 1.14-3.29, P<0.001). Subgroup analysis based on ethnicity showed that, compared to the healthy controls, serum resistin levels were markedly higher in psoriasis patients in both Asian and Caucasian populations (Asians: SMD=3.27, 95%CI=1.62~4.91, P<0.001; Caucasians: SMD=0.91, 95%CI=0.28~1.54, P<0.001). CONCLUSIONS: Based on our results, we conclude that serum resistin level in psoriasis patients is higher than healthy controls, and raises the possibility that elevated serum resistin levels may be a novel diagnostic marker in psoriasis and may predict the occurrence of co-morbidities in psoriasis patients.

[Clinical characteristics and survival of peripheral T-cell lymphoma-not otherwise specified: a report of 57 cases].

OBJECTIVE: To analyze the clinical characteristics and survival data of 57 patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). METHODS: The medical records of 57 patients with PTCL-NOS classified according to the revised REAL-WHO criteria, treated from Jan 1993 to Dec 2007 at the First and the Third affiliated Hospitals of Medical School of Xi'an Jiaotong University, were retrospectively evaluated by K-M univariate and COX multivariate analysis. RESULTS: 39 of the patients (68.4%) were males and 18 (31.6%) were females, aged 44 (3 - 88). Nine of the 57 patients (15.8%) were treated with chemo-radiotherapy, 43 (75.4%) with chemotherapy, 3 (5.3%) with radiotherapy, and 2 with supported treatment alone (2.5%). The overall response rate was 87.3%, with a complete remission (CR) rate of 60.0% in 55 evaluable cases. The 1-, 3-, and 5-year overall survival (OS) rates were 67.0%, 48.0% and 24.3%, respectively, with a median follow-up of 30.4 months (ranged 1-100 months). The median survival time (MST) was 36.0 months. Multivariate analysis showed that the prognostic index for T cell lymphoma (PIT) score was an independent prognostic factor for PTCL-NOS (P < 0.05), but bone marrow involvement, performance status, extranodal involvement, stage, B symptom were not independent prognostic factors. CONCLUSION: Although conventional chemotherapy yields a high response rate for PTCL-NOS, the long-term survival is still low and further investigation for optional treatment is needed.