AIM: To study the effect of Lomerizine on the activity of P-glycorprotein (P-gp) in primary cultured rat brain microvessel endothelial cells (RBMECs). METHODS: Flow cytometry was used to study the efflux of rhodamine123 (Rh123) and expression of P-gp in RBMECs. RT-PCR was used to measure the expression in mRNA level of mdr1 gene in RBMECs. Transwell model was used to detect the influence of Lomerizine on the transport of Rh123 through RBMECs monolayer. RESULTS: Lomerizine inhibited the efflux of Rh123 in RBMECs. No changes of P-gp and mdr1 gene mRNA expression were detected in RBMECs after the treatment with 30 μmol·L-1 Lomerizine for 72 h. In the study of Transwell model, Lomerizine increased significantly the transport of Rh123 through RBMECs monolayer from upper compartments to lower compartments, and inhibited obviously the transport in reverse direction. CONCLUTION: The effect of Lomerizine on the activity of P-gp was mainly via its direct inhibitory effect on the function of P-gp in RBMECs and the transport of P-gp substrates in BBB may be affected by lomerizine.

Objective To establish a culture protocol for Th17 cells in vitro and evaluate the effect of curcumin on the differentiation and functions of Th17 cells and explore the related mechanisms. Methods Splenic CD4+CD25- T cells of C57BL/6 mice were isolated and purified with magnetic bead methods, and were co-cultured with plate-bound anti-CD3 and anti-CD28 antibodies and with transforming growth factor (TGF)-β, interleukin (IL)-6, IL-23, anti-interferon-γ antibody and anti-IL-2 antibody for Th17-polarization. The cultured Th17 cells were allocated into four groups: the control group, in which T cells were cultured on the basis of the above protocol; the low-concentration curcumin (CM-L, 5 μmol/L) and high-concentration (CM-H, 25 μmol/L) curcumin groups, and sirolimus (SRL, 100 ng/ml) group. The proportion of Th17 cells was detected with flow cytometry, and the mRNA expression of retinoic acid-related orphan receptor (ROR)γt, IL-17A, IL-21 was examined with real-time quantitative polymerase chain reaction. Finally, the protein expression of RORγt and the phosphorylation levels of signal transducer and activator of transcription (STAT) 3 were measured using western blotting analysis. Results The proportion of Th17 cells in the freshly isolated CD4+CD25- T cells was (3.1 ±0.4)%, whereas the proportion of the cells cultured with the protocol could get [(54.1±3.4)%, P<0.01]. As compared with the control group, the Th17 cells proportion in CM-L, CM-H and SRL groups was significantly decreased [CM-L (40.3±2.8)%, CM-H (25.8±2.3)%, SRL (25.0±2.0)%versus the control (54.1±3.4)%, t=6.15, 12.63, 12.97, P<0.01], and no marked difference was seen between CM-H group and SRL group (ft>0.05). Moreover, the mRNA levels of RORγt, IL-17A and IL-21, the protein expression of RORγt and the phosphorylation levels of STAT 3 in CM-L, CM-H and SRL groups were also lower than those in the control group (IL-17A mRNA: CM-L 0.81±0.05, CM-H 0.61±0.05, SRL 0.58±0.05, Control 1.01 ±0.11, t=4.81, 8.52, 8.89; IL-21 mRNA: CM-L 0.73±0.06, CM-H 0.49±0.03,SRL 0.59±0.03, Control 1.12±0.11, t=5.98, 9.22, 7.95, P<0.01). The mRNA level of IL-21 in the CM-H group was lower than that in the SRL group (P<0.05). Conclusion In vitro, curcumin can inhibit the differentiaton of splenic CD4+CD25- T cells into Th17 cells in the setting of Th 17-polarization and inhibit the expression of IL-17A and IL-21 mRNA, which is associated with the inhibitive effect of curcumin on RORγt expression and STAT 3 phosphorylation.

RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of insulin receptor substrate 2 (IRS-2) in the muscle of smoking rats. The mRNA and protein expressions of IRS-2 in the smoking subgroups fed with normal diet or high-fat diet were significantly lower than those in corrsponding control groups (0.27±0.02 vs 0.41±0.25, 0.40±0.04 vs 0.51±0.02 for mRNA; 2.91±0.42 vs 4.90±0.29, 2.43±0.36 vs 3.80±0.30 for protein, all P<0.01). There were no differences in mRNA and protein expressions of IRS-2 between the smoking group of diabetic rats and the matched control rats (P>0.05). The variation of gene expression of IRS-2 may be involved in the mechanism of insulin resistance caused by smoking.

Objective: To evaluate the safety and feasibility of hybrid thoracoscopic surgery and catheter ablation in treating the patients of long-standing persistent atrial fibrillation (AF) with preliminary experience. Methods: A total of 15 consecutive relevant patients treated in our hospital by hybrid thoracoscopic surgery and catheter ablation from 2014-04 to 2016-03 were studied. The average AF time was (4.0±3.9) years including 13 male. All patients received thoracoscopic surgical ablation including pulmonary vein isolation, left atrial (LA) posterior wall isolation, Waterston's groove Ganglionated plexi ablation by bipolar radiofrequency ablation clamp and LA appendage removal, Marshall ligament dividing. Then establishing LA 3D-modeling, based on LA 3D voltage mapping, catheter ablation was conducted to reinforce surgical ablation or modification in order to confirm bidirectional blocking. Meanwhile, LA ridge and mitral isthmus ablation was performed, some patients received LA anterior wall and tricuspid isthmus ablation. The patients were followed-up at 3, 6 and 12 months after the procedure. Results: 13 patients were restored to sinus rhythm after the procedure and no operative complications occurred. The average follow-up time was (12.1±11.5) months. 2 patients with recovered sinus rhythm had re-catheter ablation since atrial flutter at 3 months post-procedure and sinus rhythm was restored. The overall success rate was 86.7% (13/15), no patient had anti-arrhgthmia medication. Conclusion: Hybrid thoracoscopic ablation and catheter ablation have been a minimally invasive, safe and effective method in treating the patients of long-standing persistent AF.

Objective:To investigate the efficacy of different surgical treatments for hypertensive cerebral hemorrhage in older adult patients and their effects on traumatic stress and cerebral edema.Methods:A total of 100 older adult patients with hypertensive cerebral hemorrhage who received treatment in Zhejiang Xin'an International Hospital from January 2018 to June 2020 were included in this study. They underwent either craniotomy (craniotomy group, n = 50) or hard channel minimally invasive puncture drainage (minimally invasive puncture group, n = 50) according to the willingness of patients and their close relatives. Perioperative indexes, Barthel index after treatment, nerve injury indexes before and after treatment, prognosis related indexes, trauma stress indexes and brain edema were compared between the two groups. Results:Operative time, intraoperative blood loss and postoperative hospital stay in the craniotomy group were (147.21 ± 31.35) minutes, (289.74 ± 22.75) mL and (42.74 ± 6.82 ) days, respectively, which were significantly longer or greater than (41.88 ± 7.19) minutes, (4.62 ± 0.88) mL and (16.27 ± 4.02) days in the minimally invasive puncture group ( t = 38.73, 62.17, 23.17, all P < 0.001). Barthel index at 1 and 3 months after treatment in the minimally invasive puncture group was (63.11± 9.64) and (93.51 ± 11.38), respectively, which was significantly greater than (44.78 ± 8.85) and (81.29 ± 10.37) in the craniotomy group ( t = 3.17, 6.21, both P < 0.05). Before treatment, there were no significant differences in nerve injury index, prognosis index, trauma stress index and brain edema between the two groups (all P > 0.05). At different time points after treatment, each indicator in the minimally invasive puncture group was significantly superior to that in the craniotomy group (all P < 0.05). Conclusion:Hard channel minimally invasive puncture drainage exhibits advantages over traditional craniotomy in the treatment of hypertensive cerebral hemorrhage in older adult patients. Hard channel minimally invasive puncture drainage can more greatly reduce injury to brain tissue, better control nerve injury and brain edema, and more remarkably improve patient's quality of life than traditional craniotomy.

Objective To compare the clinical significance of peripheral blood neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in predicting prognosis of patients with hepatocellular carcinoma (HCC).Methods The clinical data of 661 patients with HCC were retrospectively analyzed.Routine peripheral blood test results were used to calculate the NLR and PLR,and the receiver operating characteristic (ROC) curves were drawn.Using the thresholds of NLR and PLR,the patients were divided into the low NLR group and the high NLR group,and the low PLR group and the high PLR group.Overall survival (OS) and disease free survival (DFS) were evaluated by the Kaplan-Meier method.Independent prognostic predictors were determined by the Cox proportional hazard model.Results The NLR and PLR thresholds were 2.790 and 99,respectively.Analysis of the ROC curves showed higher NLR and PLR were significantly associated with poorer OS and DFS (all P ＜ 0.05).Multivariate analysis showed that NLR was an independent risk factor of OS and DFS (both P ＜ 0.05).The results remained unchanged when the NLR was further analyzed by applying different cut-off values of 2.810 and 3.In subgroup analysis,NLR remained an independent factor of Barcelona Clinical Liver Cancer staging system (BCLC) 0/A/B (P ＜ 0.05 for all measurements).Conclusion An elevated preoperative NLR could be a better prognostic predictor for HCC patients in comparison with PLR,especially for BCLC 0/A/B patients.

Objective To detect the positive rates of antibodies against avian influenza virus (AIV) subtypes H5, H6, H7 and H9 among people in poultry occupations in Guangdong province and to analyze the transmission of various subtypes of AIV from poultry to human contacts for the prevention and control of novel AIV infection in human beings.Methods Serum specimens were collected from 1066 peo-ple in poultry occupations ( occupational group) and 205 people not in poultry occupations ( non-occupational group) in 10 cities of Guangdong province.The inactivated AIV strains, isolated from poultry or environment of Guangdong province, were used as antigens to detect antibodies against AIV subtypes H5, H6, H7 and H9 by using the hemagglutination inhibition ( HI) assay.Results The positive rates of antibodies against AIV subtypes H5, H6, H7 and H9 carried by people from the occupational group were respectively 0.44%, 0%, 0.30%and 0.30%in 2013 and 1.08%, 0.0%, 0.0%and 0.27%in 2014.Only the anti-H9 anti-bodies were detected in serum samples collected form people in the non-occupational group in 2013 with a positive rate of 0.95%.No significant differences with the positive rates of anti-AIV antibodies were found between the occupational group and the non-occupational group.However, the geometric mean titer ( GMT) of anti-AVI antibodies in people from the occupational group was higher than that of the non-occupational group.Conclusion Although a grand spread of AIV from avian to human is not likely to happen yet, con-tacting with poultry is the risk factor for AIV infection in Guangdong population.A long-term surveillance of anti-AIV antibodies in serum should be strengthened among people in poultry occupations for the timely pre-vention and control of novel AIV outbreak.

Objective To investigate the efficacy of transcatheter selective cystic arterial infusion chemotherapy embolization in the treatment of invasive bladder cancer with hemorrhage.Methods 81 cases of with invasive bladder cancer and hemorrhage treated by superselective intervention in hospital were selected,as well as postoperative complications and tumor volume changes were recorded in followG up.Results The success rate of intubation and embolization was 100%,the immediate hemostasis rate was 97.53%,and the preoperative bladder tumor volume (4.08±1.66)cm was significantly larger than that of the six months after surgery (3.45±1.33)cm.Conclusion Superselective cystic arterial perfusion embolization is a safe and effective treatment for patients with invasive bladder cancer complicated with hemorrhage.

Objective To investigate the clinical curative effect and significance of partial splenic artery embolization (PSE) for the treatment of patients with hypersplenism at high altitude region. Methods The clinical data of 66 patients with cirrhosis complicated by portal hypertension and hypersplenism, who lived in Xining City of Qinghai Province, the high altitude region in China, and were admitted to authors' hospital during the period from March 2015 to December 2016 to receive PSE, were retrospectively analyzed. White blood cell (WBC) count, red blood cell (RBC) count and platelet (PLT) count were calculated at one day before operation as well as at one, 7, 30 and 90 days after operation. Results The technical success rate of PSE was 100％. The mean WBC count determined at one, 7, 30 and 90 days after PSE was obviously different from that determined at one day before PSE, the differences were statistically significant (P＜0. 05). Conclusion For the treatment of patients with cirrhosis complicated by portal hypertension and hypersplenism, who live at high altitude region, PSE has reliable curative effect, therefore, this therapy is worth promoting in clinical practice. (J Intervent Radiol, 2018, 27: 271-273)

OBJECTIVE: To explore the genetic basis for a fetus with renal abnormalities through whole exome sequencing and imaging examination. METHODS: Clinical data and result of medical imaging of the fetus was collected. Amniotic fluid sample was collected for the extraction of fetal DNA. Whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed that the fetus had bilateral enlargement of the kidneys with hyperechogenicity and diffuse renal cysts. Whole exome sequencing revealed that the fetus carried compound heterozygous variants of the PKHD1 gene, namely c.5137G>T and c.2335_2336delCA, which were derived from its mother and father, respectively. CONCLUSION The fetus was diagnosed with autosomal recessive polycystic kidney disease through combined prenatal ultrasonography and whole exome sequencing. The compound heterozygous variants of the PKHD1 gene probably underlay the pathogenesis in the fetus. The results have enabled prenatal diagnosis and genetic counseling for its parents.
Female ; Genetic Testing ; Humans ; Polycystic Kidney, Autosomal Recessive/genetics* ; Pregnancy ; Prenatal Diagnosis ; Receptors, Cell Surface/genetics* ; Whole Exome Sequencing