OBJECTIVE:To determinate the metabolites of ranolazine in rats by LC-MSn.METHODS:Rats were given 80 mg?kg-1 ranolazine by i.g.During 0～24 h after intragastrical administration,the sample of urine was collected and extracted by solid phase column.Extracts were determined by LC-MSn.The mobile phase consisted of acetonitrile,10 mmol?L-1ammonium acetate and glacial acetic acid at a flow rate of 0.5 mL?min-1.Fragmentation ions of ranolazine and its metabolites were determined in positive electrospray ionization by using MS,MS2 and MS3 full scans.RESULTS:Twelve phaseⅠ metabolites (O-demethylation,O-dearylation,hydroxylation,N-dealkylation and amide hydrolysis) and nine phase Ⅱ metabolites(O-glucuronidation and sulfation) were found in the sample.CONCLUSION:Ranolazine is extensively metabolized in rats.

OBJECTIVE: To establish a HPLC method for the determination of serum concentration of caffeic acid in rats and which was applied to the pharmacokinetic study of caffeic acid. METHODS: The concentrations of caffeic acid in rats were determined after intragastric (ig) administration or intravenous (iv) administration of 50 mg?kg-1 caffeic acid and the pharmacokinetic parameters of caffeic acid analyzed by Topfit 2.0. RESULTS: The main pharmacokinetic parameters of caffeic acid after ig administration of caffeic acid were as follows: Cmax: (0.56?0.12) ?g?mL-1; tmax: (0.18?0.04) h; t1/2: (0.67?0.12) h; ke: (1.05?0.20) h-1; AUC(0～t): (0.34?0.05) ?g?h?mL-1. The main pharmacokinetic parameters of caffeic acid via iv administration were as follows: t1/2: (0.45?0.05) h; ke: (1.55?0.18) h-1; AUC(0～t): (9.07?2.24) ?g?h?mL-1. CONCLUSION: Administered intragastrically, caffeic acid was characterized by rapid absorption, short elimination half life (t1/2) and low absolute bioavailability in rats.

OBJECTIVE:To study the metabolite and excretion of polydatin (Trans-resveratrol-3-O-glucoside,TRG) and its metabolites in Beagle dog feces,and provide experimental basis for the new drug development of TRG. METHODS:4 Beagle dogs were intragastrically administrated TRG 20％ polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the me-tabolites of TRG in dog feces after 12-24 h of administration,and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol(TR)in feces samples after 0-12,12-24,24-36,36-48,48-72,72-96 h of administration. RESULTS:TR and two sulfate conjugates of TR were found in dog feces,and TR was a major metabolite, while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration,reach-ing 9.65 mg/h. Its cumulative excretion rate was 39.3％,equivalent to 67.2％ of TRG. CONCLUSIONS:After TRG is intragastri-cally administrated to dogs,TRG was mainly excreted in the form of TR via dog feces.

Objective Tamm-Horsfall protein (THP) may play a role in kidney stone formation.The article aimed to conduct a preliminary study on the role of THP in kidney stone formation by investigating the changes of THP in rat urine, pathological changes of renal tissue and the formation of calcium salt crystals after establishing CNPs rat model of kidney stones.Methods Stone samples of 40 patients from February to June 2015 in our department were collected to establish the model of CNPs-induced kidney stone in rats and prepare CNPs suspension.48 SD rats were randomly divided into experimental group (group A) and blank control group (group B).Group A were injected with CNPs and the same amount of sterile saline injection in the group B.The urine of rats was collected after injection at 3h, 6h, 12h, 24h, 1w, 2w, 4w and 8w.ELISA were applied to detect THP levels in the urine.Then the rats were killed to take the kidney tissue.HE staining was used to investigate the pathological changes of the cells and evaluate the formation of the calcium salt crystals.Results THP levels in group A at 24h, 1w, 2w, 4w and 8w ([166.03±3.02], [173.50±1.78], [174.55±2.05], [176.54±2.45], [177.11±1.76]pg/mL) were significantly higher than that at 3h(165.89±2.23pg/mL)(P<0.05), which was the same case in comparison with those of group B ([157.65±2.22], [156.54±1.43], [159.45±3.21], [158.63±2.98], [157.33±2.05]pg/mL).Compared with the calcium salt crystal score at 6h (1 point), the scores at 3,6,12,24h (average score 2 points) increased.At 2w the score increased significantly to 3 points and reached the top score(6.7points) at 8w, which was of significant difference.The score of calcium salt crystals was in positive correlation with THP content (r=0.843,P<0.05).Conclusion THP in urine may contribute to the aggregation of calcium salt crystals and the formation of kidney stones.

OBJECTIVETo establish a method for the prenatal diagnosis of 22q11 microdeletion syndrome.

METHODSBACs-on-Beads (BoBs) and fluorescence in situ hybridization (FISH) were performed on a fetus for whom amniotic chromosomal culturing has failed and a pair of twin fetuses suspected for 22q11 deletion syndrome.

RESULTS22q11 microdeletion was detected in all 3 fetuses by prenatal BoBs as well as FISH, with only one red signal detected at the DiGeorge/VCFS N25 site and two green signals on the 22q13.3 ARSA site.

CONCLUSIONThe combination of prenatal BoBs and FISH can provide a method for the prenatal diagnosis of 22q11 microdeletion.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To analyze the intrauterine phenotype and genotype of eight fetuses carrying a 16p11.2 microdeletion. METHODS: 5100 fetuses undergoing routine prenatal diagnosis were subjected to single nucleotide polymorphism-based microarray (SNP-array) analysis. Fetuses harboring a 16p11.2 microdeletion were analyzed for their ultrasonographic characteristics. RESULTS: Eight fetuses were found to harbor a microdeletion in the 16p11.2 region. Among these, six had a typical 500-600 kb deletion, while the remaining two had an atypical 220 kb deletion at the distal part of 16p11.2. Four fetuses showed vertebral malformations, two had mild left ventriculomegaly, one had hydrocephalus, and one had pulmonary valve stenosis with regurgitation. The parents of five fetuses have accepted pedigree verification, and the results confirmed that the 16p11.2 microdeletions carried by fetuses all had a de novo origin. CONCLUSION The intrauterine phenotypes of fetuses carrying a 16p11.2 microdeletion may be variable, and the deletion can be effectively detected with the SNP-array assay.
Chromosome Deletion ; Female ; Fetus ; Genetic Testing ; Humans ; Phenotype ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.
22q11 Deletion Syndrome/diagnostic imaging* ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; Prenatal Diagnosis ; Ultrasonics

OBJECTIVE: To analyze the ultrasonographic phenotype and result of genetic testing in six fetuses carrying a 17q12 microdeletion. METHODS: Chromosomal microarray analysis (CMA) was carried out for 6200 pregnant women undergoing prenatal diagnosis from December 2016 to May 2021. RESULTS: CMA has identified 6 fetuses with a microdeletion in the 17q12 region, which spanned approximately 1.4 Mb and encompassed at least 13 OMIM genes. All fetuses have shown bilateral renal parenchymal echo enhancement. Four fetuses also had other ultrasonographic phenotypes. The parents of 4 fetuses had refused parental verification, whilst the remaining two fetuses were confirmed to be de novo in origin. CONCLUSION The prenatal ultrasonographic phenotype of 17q12 microdeletion is mainly enhanced bilateral renal parenchymal echos. CMA can facilitate detection of the 17q12 microdeletion.
Female ; Humans ; Pregnancy ; Genetic Testing ; Phenotype ; Fetus/diagnostic imaging* ; Prenatal Diagnosis ; Parents

ObjectiveTo explore the effect of Suanzaoren Tang combined with Ziwu Liuzhu acupuncture on the vertebral artery hemodynamics， inflammatory cytokines， and neurotrophic factors in the patients with cervical insomnia with syndrome of deficiency of both heart and spleen. MethodThe random number table method was employed to assign 164 patients with cervical insomnia with syndrome of deficiency of both heart and spleen treated in the First Clinical Medical School of Guangzhou University of Chinese Medicine from January 2018 to June 2021 into a control group and an observation group. The control group was orally administrated with 1-2 mg estazolam tablets before bed for 4 weeks， and the observation group with Suanzaoren Tang combined with Ziwu Liuzhu acupuncture for 4 weeks. The therapeutic efficacy and safety were observed. The Pittsburgh Sleep Quality Index （PSQI） score， polysomnography monitoring results， hemodynamics parameters of vertebral artery， and serum levels of inflammatory cytokines and neurotrophic factors were compared before and after treatment. ResultExcept 4 dropouts， the remaining 160 patients were included in this study， with 80 patients in each group. The observation group had higher total effective rate than the control group ［92.50% （74/80） vs. 80.00% （64/80）， χ²=5.270， P<0.05］. Compared with that before treatment， the therapies in both groups decreased the PSQI score， sleep latency time， awakening time， awakening times， serum levels of interleukin-1β （IL-1β）， C-reactive protein （CRP）， and tumor necrosis factor-α （TNF-α） （P<0.01）. Meanwhile， they increased the proportion of rapid-eye-movement （REM） sleep， the diastolic blood flow velocity （Vd）， systolic blood flow velocity （Vs）， and mean blood flow velocity （MFV） of vertebral artery， as well as the serum levels of brain-derived neurotrophic factor （BDNF） and glial cell-derived neurotrophic factor （GDNF） （P<0.05， P<0.01）. Moreover， the observation group had lower PSQI score， sleep latency time， awakening time， awakening times， and serum IL-1β， CRP， and TNF-α levels （P<0.01） and higher proportion of REM sleep， Vd， Vs， MFV of vertebral artery， and serum BDNF and GDNF levels （P<0.05， P<0.01） than the control group. ConclusionZiwu Liuzhu acupuncture combined with Suanzaoren Tang can improve blood circulation of vertebral artery， reduce the serum levels of inflammatory cytokine， and increase the serum levels of neurotrophic factors to improve the sleep quality of the patients with cervical insomnia with syndrome of deficiency of both heart and spleen.

Objective To explore the clinical value of the third-generation hybrid capture nucleic acid detection technology （DH3） typing detection of human papillomavirus （HPV） combined with thin-prep cytology test （TCT） in screening cervical cancer. Methods A total of1 582 female patients who received HPV and TCT cervical screening in Liuzhou Workers Hospital， Fourth Affiliated Hospital of Guangxi Medical University， from October 2020 to March 2021， were selected for this retrospective analysis. The cervical histopathological diagnosis was used as the gold standard to evaluate the diagnosis accuracies of HPV and TCT test results. Results Among the 1 582 patients， 334 were positive for HPV and 1 248 were negative； 234 were positive for TCT and 1 348 were negative； 180 were positive for histopathological diagnostic and 1 402 were negative. The sensitivity of HPV detection was 100%， the positive predictive value was 53.9%， the specificity was 89.0%， and the negative predictive value was 100.0%. In the HPV typing test， the positive rate for high-risk types 16/18 was 94.8%， and the positive rate for other 12 high-risk types was 73.8%. There was a little difference between TCT test and pathological test， and the detection consistency rate of high-grade squamous intraepithelial lesions and squamous carcinoma was same. Conclusion HPV testing combined with TCT to screen cervical cancer can reduce the misdiagnosis rate by a single test. The classification test is helpful for the hierarchical management of patients， and has a high clinical value for examination triage and grade screening.