Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

Breast cancer with an initial gastrointestinal presentation: a case report and literature review.

The most common sites of breast cancer metastasis are the lymph nodes, lungs, bones, and liver. Gastrointestinal (GI) metastasis is relatively rare and often occurs within several years after a breast cancer diagnosis. Most patients experience abdominal pain, anorexia, bleeding, vomiting, and other digestive system symptoms, symptoms which are difficult to distinguish from primary gastric cancer. There is no characteristic change seen under a digestive tract endoscopy, and the difference in morphology under the pathological microscope from that of primary poorly differentiated gastric adenocarcinoma is so small that it can easily cause a misdiagnosis. This paper reports the case of 46-year-old female patient whose first symptom was GI discomfort. She was hospitalized for GI surgery with an unknown medical history, but, during the preoperative examination, multiple breast masses were found on both sides, which were proved by pathology to be invasive lobular cancer. According to the medical literature, bilateral breast cancer with gastric metastasis is very rare, and, so far, this is the first reported case. Despite it being a rare phenomenon, it is necessary to be aware of the possibility of metastatic lobular carcinoma in the diagnosis of poorly differentiated gastric adenocarcinoma by biopsy.

Clinical significance of analysis of the level of blood fat, CRP and hemorheological indicators in the diagnosis of elder coronary heart disease.

OBJECTIVE: To investigate the levels of blood fat, C-reactive protein (CRP) and hemorheological indicators in the elder patients with coronary heart disease (CHD), so as to provide evidence for prospective study and treatment of elder CHD. METHODS: We collected the clinical data of 127 elder CHD patients who admitted to this hospital between July 2016 and December 2017 to detect the levels of blood fat, CRP and hemorheological indicators. RESULTS: In elder CHD patients, levels of the total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-C) were significantly higher than the normal reference, and comparison with the control group also showed significant increases (p < 0.01); average levels of the high-density lipoprotein cholesterin (HDL-C), phospholipid (PL), lipoprotein a [LP (a)] and free fatty acid were in the range of normal reference. Abnormal levels of TC, TG, LDL-C and HDL-C were identified in 59.06%, 58.27%, 51.18% and 18.11% of the elder CHD patients, most of which were concomitant with obesity or hypertension, and levels of these indicators were significantly higher than those in the control group with statistically significant differences (p < 0.01). Comparisons of the age, gender distribution, hypotension, exercise and sleep showed that differences had no statistical significance (p > 0.05). In comparison with the control group, the levels of CRP, the whole blood viscosities at high and low shears, plasma viscosity, hematocrit value, aggregation index and rigidity index of red blood cells (RBC) were all higher than those in the control group, and the differences had statistical significance (p < 0.01). However, the erythrocyte sedimentation rate (ESR), deformity index of RBC, blood flow rates in the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), terminal internal carotid artery (TICA), posterior cerebral arteries (PCA), vertebral arteries (VA) and basilar artery (BA) were significantly lower than those in the control group, and the differences had statistical significance (p < 0.05 or 0.01). CONCLUSION: In elder CHD patients, anomaly is mainly seen in levels of TC, TG and LDL-C with concentrated, adhesive and aggregating blood.

Nonlinear pharmacokinetic properties of mildronate capsules: a randomized, open-label, single- and multiple-dose study in healthy volunteers.

Mildronate has been used as antianginal drug in parts of Europe for many years, but its pharmacokinetic (PK) properties in humans remain unclear. This study was designed to assess and compare the PK properties of mildronate capsules after single escalating oral dose and multiple doses in healthy Chinese volunteers. Volunteers were randomly assigned to receive a single dose of 250, 500, 1000, 1250 or 1500 mg of mildronate capsules. Those who received the 500-mg dose continued on the multiple-dose phase and received 500 mg three times a day for 13 days. Plasma drug concentrations were analysed by ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Tolerability was assessed throughout the study. A total of 40 Chinese volunteers were enrolled in the study. No period or sequence effect was observed. Area under the concentration and C(max) were increased proportionally with the dose levels, whereas t(1/2) and V(d)/f were dependent on the dose. Nonlinear PK properties were found at doses of 250-1500 mg. There was an accumulation after multiple-dose administration. No serious adverse events (AEs) were reported in the PK study. The formulation was well tolerated.

Validated LC-MS/MS assay for the quantitative determination of nalbuphine in human plasma and its application to a pharmacokinetic study.

A solid-phase extraction-liquid chromatographic-tandem mass spectrometry method for the determination of nalbuphine concentrations in human plasma has been developed. Samples (1 mL) were extracted using a Strata™-X solid phase extraction cartridges. Chromatographic separation of nalbuphine and naloxone (internal standard) was achieved on a Phenomenex Kinetex PFP (2.6 µm, 100 A, 100 × 2.1 mm) column using a mobile phase consisting of 0.1% formic acid, 15 mM ammonium acetate in deionized water and acetonitrile (60:40, v/v). The flow rate was 0.3 mL/min and the total run time was 2 min. Detection of the analytes was achieved using positive ion electrospray ionization via multiple reactions monitoring mode. The mass transitions were m/z 358 → 340 for nalbuphine and m/z 328 → 310 for naloxone. The assay was linear over the concentration range 0.50-500.00 ng/mL, with correlation coefficients ≥0.995. The lower limit of quantitation was set at 0.5 ng/mL plasma based on an average signal-to-noise ratio of 44.79. The intra- and inter-day precision was less than 8.07% in terms of relative standard deviation and accuracy ranged from 94.97 to 106.29% at all quality control levels. The method was applied successfully to determine nalbuphine concentrations in human plasma samples obtained from subjects receiving intravenous administration of nalbuphine. The method is rapid, sensitive, selective and directly applicable to human pharmacokinetic studies involving nalbuphine.

[Clinical characteristics and ultrastructural features of livers in children with Wilson disease manifested mainly as hepatic injuries].

OBJECTIVES: To study the feasibility and possibility to diagnose Wilson disease with electronmicroscopical examination of liver biopsies. METHODS: Clinical analysis, histological observation and ultrastructural examination were performed on 15 children with Wilson disease. RESULTS: All 15 subjects had symptoms of hepatic disorders, such as jaundice. Morphological signs of hepatocyte injury in three phase, namely steatosis, mitochondrion changes and cholestasis in bile canaliculi of the early phase, nucleus injury, dilation of endoplasmic reticulum, increase of lysosomes and appearance of residual bodies of the second phase, and massive autophagy and cirrhosis of the late phase were shown. A few inflammatory cells in the liver specimens were observed. Accumulation of copper in lysosomes and autophagosomes was found by energy-dispersion X-ray. CONCLUSION: The diagnostic signs for Wilson disease are autophagosomes in hepatocytes, cirrhosis accompanied with a few of inflammatory cells. A certain diagnosis of the disease depends on the finding of copper accumulation in hepatocytes.