Novel MSX1 variants identified in families with nonsyndromic oligodontia / 国际口腔科学杂志·英文版

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.

Distribution of 5-FU in rat hepatoma, liver tissue and plasma after locoregional infusion / 中国癌症杂志

Background and purpose: Locoregional infusion chemotherapy such as hepatic artery, or hepaticportal vein infusion is one of the most important treatments for hepatocelluar carcinoma. This study was aimed to investigate the distribution of fluorouracil(5-FU) in rat hepatoma, liver tissue and plasma after administrated by caudal vein or locoregional routes of hepatic artery, hepaticportal vein, and hepaticportal vein with ligated hepatic artery. Methods:Twenty-four tumor-bearing rats were divided into 4 groups randomly, and they were infused with 5-FU through peripheral vein(caudal vein), hepatic artery, hepaticportal vein or hepaticportal vein with ligated hepatic artery, which dose was 20 mg/kg. High performance liquid chromatography was adopted to measure the content of 5-FU in hepatoma, liver tissue and plasma, and the drug penetration rate among them were calculated. Results:The group of hepaticportal vein with ligated hepatic artery reached the highest concentrations of 5-FU in live tissue and hepatoma, which concentrations were (22.1±9.5)μg/g and (16.4±7.2)μg/g. Then was the hepatic artery group, and the concentration of the hepaticportal vein group in the hepatoma focus was much smaller than the former 2 groups, which was (8.9±3.7)μg/g. The peripheral vein group got the lowest concentrations both in the liver tissue and hepatoma, which were (9.4±3.7) and (4.3±2.2)μg/g. The concentrations of 5-FU in the plasma in the peripheral vein group, the hepatic artery group, the group of hepaticportal vein with ligated hepatic artery and the hepaticportal vein group were (26.8±12.5), (16.4±9.7), (15.9±10.1) and (14.9±8.5)μg/mL, which indicated that the drug concentrations of the latter 3 groups were much lower than the former group. The hepatoma/plasma penetration rate of 5-FU in the group of hepaticportal vein with ligated hepatic artery, the hepatic artery group, the hepaticportal vein group and the peripheral vein group were 103.47%, 92.94%, 59.58% and 16.08%. Conclusion: Compared to the peripheral venous bolus injection, locoregional infusion could significantly increase the concentrations of chemotherapy agent in hepatoma focus and liver tissue, and decrease the drug distributions in peripheral blood. And the infusion through hepaticportal vein with ligated hepatic artery and through hepatic artery reaches higher concentrations in the hepatoma focuses, which indicate that they are 2 practical and promising routes for the locoregional chemotherapy of hepatoma.

Experimental study on concentrations and pharmacokinetics of antibiotics in bile and evaluation of their microbicidal potential / 中华外科杂志

<p><b>OBJECTIVE</b>To study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential.</p><p><b>METHODS</b>Thirty-six health rabbits were randomly divided into 6 groups, and each group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was isolated and cumulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was collected at different time points after administration, and the concentration of antibiotics of bile was assayed by high performance liquid chromatography. The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC)).</p><p><b>RESULTS</b>The C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 ± 3 023) mg/L and (1.97 ± 1.23) h, ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h, cefoperazone (5 215 ± 2 225) mg/L and (0.89 ± 0.13) h, meropenem (31.97 ± 12.44) mg/L and (0.36 ± 0.11) h, levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h, metronidazole (28.2 ± 10.2) mg/L and (0.81 ± 0.33) h, respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T(>MIC), and their bactericidal indexes were (62.1 ± 23.6) - (993.8 ± 377.9) and (164.8 ± 69.0) - (659.3 ± 275.9), their T(>MIC) were (6.00 ± 2.53) - (8.00 ± 0.00) h and (6.33 ± 1.97) - (8.00 ± 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the smallest, which were (2.1 ± 1.2) - (8.3 ± 4.6) and (0.54 ± 0.25) - (2.67 ± 1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal indexes and T(>MIC) were (4.3 ± 1.0) - (69.2 ± 15.5) , (1.42 ± 0.65) - (8.00 ± 0.00) h and (2.0 ± 0.8) - (1 031.3 ± 401.4) , (0.29 ± 0.10) - (1.83 ± 0.26) h. The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h.</p><p><b>CONCLUSIONS</b>The bile concentrations of six antibiotics all exceed their effective bactericidal concentrations. The concentration-time curves of piperacillin, cefoperazone, meropenem and metronidazole conformed to one-compartment model, and ceftriaxone and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T(>MIC), so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic, the microbicidal potential of metronidazole is high.</p>

Management of main hepatic vein injury in hepatectomy for hepatic neoplasm of segment Ⅷ / 中华肝胆外科杂志

Objective To summarize the experience in management of main hepatic vein injury due to hepatectomy for hepatic neoplasm of segment Ⅷ. Methods Clinical data of 64 patients suffering from main hepatic vein injury due to hepatectomy of hepatic neoplasm of segment Ⅷ in our hospital from October 1996 to October 2008 were retrospectively analyzed. Results Both the main trunks of the middle and right hepatic vein were injured in 34 patients, single right hepatic vein in 13 and middle hepatic vein in 17. In these patients with hepatic vein injury, the main trunk of the hepatic vein was repaired in 39, vessels ligated in 12 and direct liver wound surfaces sutured in 12. The hepatectomy and hemostasis were successfully performed during operation in all patients. After operation, 3 patients had active bleeding and 2 patients were reoperated on to sew up the bleeding points by wadding with the gelatin sponge and discharged after rehabilitation. One patient gave up treatment and was discharged automatically. Conclusion Main hepatic vein injury in hepatectomy of hepatic neoplasm of segment Ⅷ can be managed effectively by hepatic vein repair, hepatic vein ligation and suture of the liver section that can be chosen to control the bleeding of hepatic vein injury according to the actual conditions.

Assessment of Biliary Excretion of Ceftriaxone Sodium in Humans / 医学研究杂志

Objective To study biliary excretion of ceftriaxone sodium in humans. Methods Twelve biliary calculi patients were infused with a single dose of 2.0g ceftriaxone half an hour before operation and the common bile duct bile and gallbladder bile samples were coUected in the operations. The bile drug concentrations were assayed by HPLC. Results The results of clinical study on the bile drug showed that the concentrations (C) of ceftriaxone in common bile duct and gallbladder were (264.43±166.46) μg/ml and (85.39 ±48.16) μg/ml, respectively. Conclusion Ceftriaxone reaches high concentrations in humans' bile, and it could be chosen as a good antibiotics for the treament of biliary infection.