AIM To evaluate bioavailability, biocompa- tibility and biodegradability of an injectable microsphere sustained release preparation of naltrexone(NTX) in 4 dogs. METHODS Pharmacokinetic data of NTX and remained NTX in microspheres in injection site were studied using high performance liquid chromatography(HPLC)-electrochemical detection with naloxone(NLX) as internal standard. Biocompatibility of the microspheres was assayed by histological examination. RESULTSPharmacokinetics of NTX after an intramuscular dose of 0.5 or 1.0 mg*kg-1 NTX indicated a plasma clearance range of 0.66 to 0.73 L*min-1 and a t1/2β range of 60.0 to 67.2 min. After a 1-week washout period without medication, NTX microspheres injection period about 4 weeks followed. After injection of 1.0 g of microspheres containing (296.5±2.1)mg of NTX, mean blood concentrations of NTX exceeded 1 μg*L-1 for 26-28 d, and cmax per dose (mg*kg-1) was only 1% of that after NTX dosing. It was estimated that approximately (93.0±4.1)% of the administered dose was absorbed after microspheres injection in 4 dogs. There were no serious adverse effects other than light tissue irritation. CONCLUSIONThis NTX microspheres preparation provides a safe, complete and sustained release of the drug for about one month.

The aim of the study is to investigate the effect of salvianolic acid B (SalB) on blood-brain barrier (BBB) in rats after cerebral ischemia-reperfusion, and to illustrate its possible mechanisms. Cerebral ischemia-reperfusion was induced by middle cerebral artery occlusion in rats. The break-down of BBB was indicated by extravasations of immunoglobulin (IgG) monitored with immunohistochemistry. The expression of MMP-9 and NOS2 in the brain was determined by immunohistochemistry, and the expression of p-p38 and p-ERK1/2 was detected by Western blotting. It was shown that on day 2 after ischemia-reperfusion the IgG accumulated around the vascular boundary zone, suggesting the break-down of BBB, and the expression of MMP-9 and NOS2 up-regulated at the same time. The result of Western blotting suggested that the expression of p-p38 and p-ERK1/2 increased. On day 7 after ischemia-reperfusion the. expression of MMP-9 and NOS2 was about the same level as day 2, the expression of p-p38 was higher than that on day 2 and the expression of p-ERK1/2 was slightly lower than that on day 2. SalB (1 and 10 mg x kg(-1)) significantly alleviated the extravasations of immunoglobulin induced by cerebral ischemia-reperfusion (P < 0.05). On day 2 and day 7 SalB attenuated the expression of MMP-9 and NOS2 (P < 0.05). SalB (10 mg x kg(-1)) reduced the expression of p-p38 and p-ERK1/2 apparently on day 2 and 7 after ischemia-reperfusion (P < 0.05). SalB (1 mg x kg(-1)) inhibited the expression of p-p38 on day 7 after ischemia-reperfusion (P < 0.05). The results indicate that SalB protects blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting the MAPK pathway.

The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard. The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3.75 mg). Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard. Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. The recovery of nicotine and the delivery of DL-nicotine were the same. The fate of absorption and distribution was two compartment model and the values of t1/2alpha was 170.31 min, t1/2beta was 263.30 min and the AUC(0-infinity) was 2.75 x 10(5) microg x L(-1) min separately. DL-nicotine can be used to calibrate the recovery of nicotine, and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat. It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.

Objective To investigate the relationsheep between colonic H2 S‐producing enzyme cystathionine‐γ‐lyase(CSE) and colonic motility in a rat model of diabetes mellitus(DM) .Methods To obtained diabetic rat models ,all rats were injected intra‐peritoneally (ip) 1% streptozotocin (STZ ,65 mg/kg) ,type 1 diabetes model was established ,nornmol conditions were observed pe‐riodically .Ten days after treatment ,production of colonic longitudinal smooth muscle strips ,organ bath recordings were used to test the colonic motility ;immunofluorescence and double immunofluorescence lableling method were performed to detect the distribution of CSE;Western blot were performed on rat colonic samples devoid of mucosa and submucosa to detect the expression of CSE .Re‐sults DM rats decreased the colonic motility(P<0 .05);CSE was strongly expressed in the cytosols of the circular and longitudinal smooth muscle cells and the nucleus of the myenteric plexus neurons ;CSE distributed in myenteric neurons in the nucleus of rat ,but the proportion of MP had no difference (P>0 .05);DM rats increased the expression of CSE in the colon devoid of mucosa and sub‐mucosa(P<0 .05) .Conclusion The decrease of colonic motility in diabetic rat may be associated with the increased production of H2 S‐producing enzyme CSE .

Objective To establish the quality standard of Radix Toddaliae Asiaticae. Methods Thin layer chromatography ( TLC) and high performance liquid chromatography ( HPLC) were used to identify and determine chloride nitidine and toddalolactone in Radix Toddaliae Asiaticae. The moisture and total ash contents were detected according to the methods recorded in appendix of Chinese Pharmacopeia (2010 edition) . Results Toddalolactone and chloride nitidine were detectable by TLC, the spots were clear and the dissociation was good. The established HPLC method was simple and accurate. The linear ranges of toddalolactone and chloride nitidine in Radix Toddaliae Asiaticae were 2.84~42.6 μg/mL and 25.6~385 μg/mL, and their recovery rates were 99.2 % ( RSD=1.12%) and 100 % ( RSD=0.71%) , respectively. The content of moisture was in the range of 75.8~98.9 mg/g and that of total ash was in the range of 12.4~33.6 mg/g. Conclusion The developed method is specific and accurate, and can provide useful reference for establishing quality standard of Radix Toddaliae Asiaticae.

Objective To explore the value of elastography score and strain rate ratio in the diagnosis of small breast malignant focus. Methods We retrospectively analyzed 22 patients with breast small malignant foci less than 10 mm. Ultrasound characteristics were summed up in breast small cancer. Results On elastogram, 2 patients scored 3, 14 scored 4 and 6 scored 5.The average strain rate ratio of all foci was 4.76, and there was correlation between it and elastography scores. Conclusion Ultrasonic elastography has important value in the diagnosis of breast small cancer.

OBJECTIVE: To determine the composition and distribution of beta-thalassemia-associated genotypes in Liuzhou area of Guangxi, China. METHODS: From January to December 2017, 13 847 individuals who came for premarital examination, maternity examination or health check were recruited with informed consent. The subjects were analyzed by reverse dot blotting (RDB) for 17 common beta-thalassemia-associated variants among the Chinese population. Individuals with inconsistent results by blood test, electrophoresis, and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene. RESULTS: In total 2098 individuals were found to harbor beta-thalassemia-associated variants, which included 2075 heterozygotes (98.90%), 12 compound heterozygotes (0.57%) and 11 homozygotes (0.52%). CD41-42 (48.43%) and CD17 (31.45%) were the most common variants. Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene, with the most common types being --SEA/aa, -a3.7/aa, aCSa/aa, -a4.2/aa. Through Sanger sequencing, rare genotypes such as beta-32/betaN, betaCD41-42/betaIVS-II-5 and betaCD30/betaN were detected. CONCLUSION Liuzhou area has a high incidence of beta-thalassemia, but with a complex variant spectrum and clinical phenotypes different from other regions. Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects. Our result may provide valuable information for the prevention and control of beta-thalassemia in this area.
China ; Female ; Genetic Counseling ; Genetic Variation ; Genotype ; Humans ; Mutation ; Pregnancy ; Prenatal Diagnosis ; alpha-Globins ; genetics ; beta-Globins ; genetics ; beta-Thalassemia ; diagnosis ; genetics

Objective:We aimed to explore a colorectal cancer risk prediction model through machine learning algorithm based on the big data in laboratory medicine.Methods:According to the labeling of colonoscopy combined with pathology or referring to the ICD-10 code, the colonoscopy patients in Shanghai Changhai Hospital from 2013.1.1 to 2019.6.30 and the outpatients and inpatients from 2010.1.1 to 2019.6.30 were divided into colorectal cancer groups and non-colorectal cancer group. Four machine learning algorithms, Extreme gradient boosting(Xgboost),Artificial Neural Network(ANN),Support Vector Machine(SVM),Random Forest(RF), are used to mine all routine laboratory test item data of the enrolled patients, select model features and establish a classification model for colorectal cancer. And the effectiveness of the model was prospectively verified in patients in the whole hospital of Changhai Hospital from 2019.7.1 to 2020.8.31.Result:A colorectal cancer risk prediction model (CRC-Lab7) including 7 characteristics of fecal occult blood, carcinoembryonic antigen, red blood cell distribution width, lymphocyte count, albumin/globulin, high-density lipoprotein cholesterol and hepatitis B virus core antibody was constructed by the XgBoost algorithm. The AUC of the model in the validation set and prospective validation set were 0.799 and 0.816, respectively, which was significantly higher than that of fecal occult blood (AUC was 0.68 and 0.706, respectively). It also has high diagnostic accuracy for colorectal cancer with negative fecal occult blood or under 50 years old.Conclusion:In this study, a colorectal cancer risk prediction model was established by mining routine laboratory big data. The model′s performance is better than fecal occult blood, and it has high diagnostic accuracy for colorectal cancer in patients with negative fecal occult blood and younger than 50 years old.

Objective:To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen.Methods:The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy.Results:A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021.Conclusions:Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.