Determination of medium- and short-chain fatty acids in feces by UHPLC-QTOF-MS/MS with pre-column derivatization / 药学学报

A pre-column derivatization and ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) method was developed for qualitative and quantitative determination of medium- and short-chain fatty acids in mice feces, and was further applied to evaluate variations in the feces of mice before and after antibiotic treatment. This animal experiment had been approved by Animal Experimental Ethics Committee of Jiangsu Province Academy of Traditional Chinese Medicine. By optimizing the derivatization conditions and UHPLC-QTOF-MS/MS parameters a new UHPLC-QTOF-MS/MS method with 3-nitrophenylhydrazine as the derivatization reagent was developed for simultaneous determination of 16 medium- and short-chain fatty acids. Validation studies showed that the linearity of the calibration curves was good (R2>0.99), the RSD of intra-day and inter-day precision was less than 10%, the repeatability RSD was less than 6%, the recovery rate was between 80% - 120% at three spiked levels, and the stability RSD was less than 7% within 36 h. The types and amounts of the detected medium- and short-chain fatty acids in feces significantly changed after the mice were treated with antibiotics. The content of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and lactic acid decreased, whereas that of heptanoic acid and succinic acid increased significantly. All these results suggest that the newly established method is accurate and reliable, and can be used for determination of medium- and short-chain fatty acids in feces.

Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial ROS Production

This study sought to evaluate the effects of Asiatic acid in LPS-induced BV2 microglia cells and 1-methyl-4-phenyl-pyridine (MPP⁺)-induced SH-SY5Y cells, to investigate the potential anti-inflammatory mechanisms of Asiatic acid in Parkinson’s disease (PD). SH-SY5Y cells were induced using MPP⁺ to establish as an in vitro model of PD, so that the effects of Asiatic acid on dopaminergic neurons could be examined. The NLRP3 inflammasome was activated in BV2 microglia cells to explore potential mechanisms for the neuroprotective effects of Asiatic acid. We showed that Asiatic acid reduced intracellular production of mitochondrial reactive oxygen species and altered the mitochondrial membrane potential to regulate mitochondrial dysfunction, and suppressed the NLRP3 inflammasome in microglia cells. We additionally found that treatment with Asiatic acid directly improved SH-SY5Y cell viability and mitochondrial dysfunction induced by MPP⁺. These data demonstrate that Asiatic acid both inhibits the activation of the NLRP3 inflammasome by downregulating mitochondrial reactive oxygen species directly to protect dopaminergic neurons from, and improves mitochondrial dysfunction in SH-SY5Y cells, which were established as a model of Parkinson’s disease. Our finding reveals that Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing NLRP3 inflammasome activation in microglia cells as well as protecting dopaminergic neurons directly. This suggests a promising clinical use of Asiatic acid for PD therapy.

Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HTR) in the hippocampus in a rat model of insomnia.</p><p><b>METHODS</b>Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HTR protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively.</p><p><b>RESULTS</b>In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HTR protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HTR (P<0.01) in the hippocampus of rats with insomnia.</p><p><b>CONCLUSION</b>FSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HTR in the hippocampus.</p>

Factors associated with anastomotic leakage after anterior resection in rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the factors associated with anastomotic leakage after anterior resection in rectal cancer with the technique of total mesorectal excision (TME).</p><p><b>METHODS</b>From January 2005 and December 2007, 738 consecutive patients with rectal cancer underwent anterior resection. The data of those patients was collected and reviewed retrospectively. The associations between anastomotic leakage and 9 patient-related variables as well as 7 surgical-related variables were examined.</p><p><b>RESULTS</b>Low rectal cancer (located 7 cm or less above the anal edge), non-specialized surgeon and transanal tube use were the risk factors associated with anastomotic leakage on univariate analysis. The anastomotic leakage rate of low-rectal cancer was significantly higher than that of high-rectal cancer (5.9% vs. 0.9%, P = 0.003). The anastomotic leakage rate of the cases operated by colorectal surgeon was significantly lower than that of the cases operated by non-specialized surgeon (3.9% vs. 11.3%, P = 0.031). There was a tendency for colorectal surgeons to operate on a greater proportion of low rectal cancer than non-specialized surgeons (72.1% vs. 52.8%, P = 0.003). The leakage rate of transanal tube group was unexpectedly higher than that in patients without transanal tube (14.5% vs. 3.6%, P < 0.001). On multivariate logistic regression analysis, diabetes mellitus (P = 0.027), distance less than 1 cm from tumor to distal resection margin (P = 0.009) and defunctioning stoma (P = 0.031) were also associated with anastomotic leakage rate besides low rectal cancer, non-specialized surgeon and transanal tube use. In a further analysis of 522 patients with low rectal cancer, the leakage rate of defunctioning stoma group was significantly lower than that of non-stoma group (2.9% vs. 8.5%, P = 0.007). By contract, the leakage rate of transanal tube group was still higher than that in patients without transanal tube (15.1% vs. 4.9%, P = 0.008) because of its poor protective effect as well as the selection bias.</p><p><b>CONCLUSIONS</b>Low-rectal cancer, non-specialized surgeons and diabetes mellitus are risk factors of anastomotic leakage after rectal surgery. A defunctioning stoma was effective in preventing leakage after low-rectal cancer surgery.</p>

3-Dimensional reconstruction of MRI in patients with polyacrylamide hydrogel injection for augmentation mammoplasty / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the effective diagnostic method for the patients with polyacrylamide hydrogen injection for augmentation mammaplasty.</p><p><b>METHODS</b>MRI scanning (layer thickness 1mm, t2 _ ps3d_ cor alignment) was performed on 23 patients with polyacrylamide hydrogen injection for augmentation mammaplasty. The data were imported into computer and processed. 3D reconstruction and analysis modules were run subsequently to do the volume reconstruction and surface reconstruction to obtain stereoscopic images of the gel and adjacent structures in virtual reality, and to calculate the volume of the hydrogel.</p><p><b>RESULTS</b>Among the 23 patients (46 breasts), the injected hydrogel with integrity capsule existed in retromammary space with no malposition in 5 cases (10 breasts). The capsule was not integrally formed and hydrogel was separately distributed with irregular edge in 6 patients (12 breasts). The pectoris major space, subcutaneous and gland invasion was found in 11 patients (22 breasts). Small amount of hydrogel sparsely distributed in mammary gland and degenerative muscular tissue in 1 patient (2 breasts) who had received extracting surgery before. The volume of hydrogel ranged from 220.309 ml to 372.371 ml (mean: 306.328 ml) in 22 untreated patients (44 breasts).</p><p><b>CONCLUSIONS</b>The volume and distribution of hydrogel can be known clearly by 3D MRI reconstruction technique. This feasible technique is helpful in removing the hydrogel completely.</p>

Recombinant Human Interleukin 11 (Mega) Promotes Thrombopoiesis in Cancer Patients with Chemotherapy-Induced Myelosuppression / 中国实验血液学杂志

A randomized, selfcross-over and placebo-controlled clinical trial has been taken to evaluated the curative efficacy of rhIL-11 (Mega) for thrombocytopenia in 29 cancer patients with severe myelosuppression induced by chemotherapy. Twenty-five micro g/kg of Mega or placebo was administered subcutaneously once daily starting 24 hours after the completion of chemotherapy, and continuing for 7 to 14 days or until the platelet count reached 300 x 10(9)/L. The results from those in 118 cases performed phase II clinical trial, showed that there were 29 cases with platelet count less than 50 x 10(9)/L in placebo cycle, but there was only 1 case in Mega cycle. The percentage of the patients with platelet count less than 50 x 10(9)/L in placebo cycle of placebo + Mega group was higher than that of Mega + placebo group. The nadir and platelet counts on day 21 after chemotherapy in Mega cycle were 2.04 and 1.43 times more than those in placebo cycle, respectively. The data show that Mega had significant thrombopoietic activity with a long lasting oction for the patients experienced severe myelosuppression. It significantly increases the likelyhood of avoiding thrombocytopenia in cancer patients undergoing chemotherapy and shortens the duration of thrombocytopenia.