OBJECTIVE: To investigate the expression and clinical significance of ZEB2 and E-cadherin mRNA and protein in nasopharyngeal carcinoma (NPC) tissues. METHOD: The expressions of ZEB2 and Ecadherin in 39 cases of NPC tissue and 12 cases of nasopharyngeal inflammation tissue were detected by Real-time PCR method and immunohistochemical technique. To assess their correlations with clinicopathological parameters of NPC and the interrelationship between them. RESULT: Both the expression of ZEB2 mRNA and protein were higher in NPC tissues than that in inflammation tissues (P < 0.05). Abnormal expression of ZEB2 mRNA and protein in NPC were significantly associated to N stage and clinic stage (P < 0.05), but the difference in expression between the different gender, age and T stage were not statistically significant (P > 0.05). Both the expression of Ecadherin mRNA and protein were higher in NPC tissues than that in inflammation tissues (P < 0.05). Abnormal expression of Ecadherin mRNA and protein in NPC were significantly associated to N stage (P < 0.05), but the different expression between the different gender, age, T stage and clinic stage were not statistically significant (P > 0.05). In NPC tissues, the expression of ZEB2 mRNA was negative correlated with the expression of E-cadherin mRNA (r = -0.367, P < 0.05). The expression of ZEB1 protein was negative correlated with the expression of E-cadherin protein (r = -0.322, P < 0.05), the differences were both statistically significant. CONCLUSION The expression of ZEB2 was up-regulated in NPC, while the expression of E-cadherin was down-regulated, their expression was significantly negative correlated, and might be associated with metastasis of NPC, ZEB2 may promote the invasion and metastasis of NPC by inhibiting the expression of E-cadherin.
Antigens, CD ; Cadherins ; metabolism ; Carcinoma ; Down-Regulation ; Homeodomain Proteins ; metabolism ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; metabolism ; Nasopharynx ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Repressor Proteins ; metabolism ; Up-Regulation ; Zinc Finger E-box Binding Homeobox 2

Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula, a traditional Chinese formula (consisting of Salviae Miltiorrhizae Radix, Polygonati Rhizoma, Notoginseng Radix et Rhizoma, Nardostachyos Radix et Rhizoma, Angelicae Sinensis Radix, and Succinum), on heart in ischemic-induced myocardial infarction (MI) rats and compare with those of Amiodarone which have been demonstrated in clinic. Methods Rats were randomly divided into Sham-operated (control), Ml + Amiodarone [5 mg/(kg·d)] (MI), and MI + Wenxin Granula [10 mg/(kg·d)] groups and left anterior descending coronary artery was occluded in each group. After left anterior descending for 12 h, standard lead Ⅱ of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia. After one month, the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function. Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+ ([Ca2+]j) and L-type calcium current (ICa-L), respectively. Results Both Wenxin Granula [10 mg/(kg·d)] and Amiodarone [5 mg/(kg·d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury. After one month, Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area (P < 0.05), but Amiodarone did not. The mechanism may involve that Wenxin Granula attenuated [Ca2+]j decreasing in MI rats. Additionally, Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period. On the other hand, electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the reduced ICa-L density in rat ventricular myocytes in MI rats. The results of LSCM showed that Wenxin Granula could recover the amplitude of [Ca2+]j decreased by heart failure during long term. Conclusion Wenxin Granula could not only inhibit the incidence of arrhythmia but also decrease the mortality, which was accompanied by recovering the amplitude of [Ca2+]j. This protective effect of Wenxin Granula may partially be mediated through changing ICa-L.as well as increasing [Ca2+]j.

Objective:To detect and analyze the spontaneous abortion tissue by Array-based comparative genomic hybridization (Array-CGH) combined with quantitative fluorescence polymerase chain reaction (QF-PCR), and provide genetic guidance for spontaneous abortion prevention and prenatal testing.Methods:A total of 345 patients who were diagnosed with spontaneous abortion at Dalian Women′s and Children′s Medical Center between July 2016 to September 2019 were continuously collected. Array-CGH combined with QF-PCR technology was used to analyze and collect abortion tissues that met the inclusion criteria.Results:QF-PCR detected a total of 213 cases of abnormal chromosome number, and Array-CGH supplemented the detection of 24 cases of abnormal chromosome structure. The genetic abnormality detection rate reached 68.7% (237/345) , and common abortion tissues′ chromosomal abnormalities in this area were detected. The incidence of abortion tissues′ chromosomal abnormalities in the elder pregnant women (≥ 35 years) and earlier trimester pregnant women (<10 weeks) was significantly increased: 84.43% (141/167) vs. 53.93% (96/178), 59.42% (205/284) vs. 9.28% (32/61).Conclusions:Array-CGH combined with QF-PCR is comprehensive and complementary. Some karyotype abnormalities are more common in abortion tissues. The elder and earlier trimester pregnant women should accept genetic counseling.

Objective:To explore the application value of copy number variation sequencing(CNV-seq) combined with chromosome karyotyping technology based on next-generation sequencing technology in prenatal diagnosis.Methods:The subjects of the study were 329 pregnant women who underwent prenatal diagnosis at Dalian Municipal Women and Children′s Medical Center from January 2019 to June 2020. The amniotic fluid samples of these pregnant women were submitted for chromosome karyotype analysis, and CNV-seq testing was performed at the same time to compare the test results of the two methods.Results:A total of 53 cases of abnormal chromosomes were detected using CNV-seq combined with chromosome karyotyping technology, with an abnormal detection rate of 16.11%(53/329). Among them, 26 cases had consistent detection results, including 22 cases of aneuploidy, 2 cases of structural abnormalities and 2 cases of mosaic; CNV-seq detected 23 cases of chromosome copy number variations that were missed by karyotyping, including 17 cases of microdeletion and 6 cases of microduplication; chromosome karyotype analysis detected 4 cases of chromosome structural abnormalities that were missed by CNV-seq, including 3 cases balanced translocation and 1 case of inversion.Conclusions:CNV-seq has obvious advantages in detecting copy number variations of small fragments, which can make up for the lack of resolution of karyotyping analysis; CNV-seq combined with chromosome karyotyping analysis can improve the detection rate of abnormal chromosomes, which is important for prenatal diagnosis meaning.

Non-small cell lung cancer (NSCLC) is a malignant tumor with rapid progress and high malignancy, accounting for 85% of all lung cancers. Treatment has shifted from traditional surgery, radiotherapy and chemotherapy to targeted therapy. Targeted therapy can prolong the survival of patients with positive driver gene fusion. With the continuous progress of biological research, targets related to NSCLC have gradually been discovered. Among the many driving genes of NSCLC, RET fusion is an important emerging target discovered in recent years. It has been confirmed to have a high incidence in non-smoking, young and low-differentiated NSCLC patients. This article reviews RET gene fusion in NSCLC, the relationship between the two and the treatment progress.

Objective : To evaluate the immune effects of inactivated H7N9 influenza vaccine. Methods : We searched several common databases（The Cochrane Library,PubMed,China Biology Medicine disc,China National Knowledge Infrastructure,etc.）for research articles about immune effects of H7N9 influenza vaccine published from the time the database built to July 10th of 2018,using H7N9 and vaccine as keywords. After screening the articles according to the inclusion and exclusion criteria,we assessed the quality of the studies and then employed seroconversion rate（SCR）as an outcome indicator to analyze the immune effects of different doses and adjuvants. Results : We recruited 5 articles on inactivated H7N9 influenza vaccine from 1 679 articles. The sample size was 2 579. The results of the meta-analysis showed that the rate difference（RD）values of SCR in each dose group after the first dose ranged from 1% to 10%,which indicated a poor protective effect;after the second dose of immunization,the RD values of SCR in the vaccines without adjuvants ranged from 13% to 19%,which was not effective enough;the RD values of SCR in the vaccines with adjuvants ranged from 62% to 69%,which met the licensing criteria for influenza vaccine;better results could be achieved when immunized with two doses of vaccines with adjuvants（ RR=1.19,95%CI：1.02-1.39）;vaccines with AS03 or MF59 at the lowest dose of 3.75 μg had the same immune effects as ones at a dose of 15 μg;vaccines with AS03（RD=89%,95%CI：85%-93%）were superior to those with MF59（RD=42%,95%CI：9%- 75%）. Conclusion Inactivated H7N9 influenza vaccines could achieve good immune effects when inoculated two doses with adjuvants,and the minimum effective dose was 3.75 μg.

ObjectiveTo investigate the tolerance, pharmacokinetics, and antiviral activity of coblopasvir hydrochloride capsules in patients with hepatitis C. MethodsA total of 36 patients with hepatitis C who were admitted to The First Hospital of Jilin University from November 2016 to January 2017 were enrolled as subjects, and four dose groups (30 mg, 60 mg, 90 mg, and 120 mg) and one placebo group were established. The subjects were administered once daily for 3 consecutive days; tolerance was evaluated on D2 and D6, and follow-up was performed on D8 and D10. The subjects were enrolled based on single dose escalation, and a multiple-dose study was conducted under the premise of good tolerance to single dose. Liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of coblopasvir hydrochloride in human body, and WinNonlin 6.4 software was used to calculate main pharmacokinetic parameters. HCV RNA load was used to evaluate antiviral activity at different time points; a one-way analysis of variance was used for comparison between multiple groups, and the LSD t-test was used for further comparison between two groups. ResultsAfter coblopasvir hydrochloride capsules were administered orally once a day at a dose of 30-120 mg, the plasma concentration and exposure of coblopasvir hydrochloride increased with the increase in dose. There were no significant differences in plasma concentration and exposure between multiple-dose administration and single-dose administration in a fasting state, without accumulation in human body. After the oral administration of coblopasvir hydrochloride capsules once a day, the subjects with HCV genotype 1b had a reduction in HCV RNA load since baseline, with the lowest level at 120 hours, and there was a significant difference in antiviral activity between different dose groups (F=14.621, P＜0.000 1), among which the 60 mg group had a significantly greater reduction than the 30 mg group (P=0.025), while there was no significant difference between the 60 mg group and the 90/120 mg group (P＞0.05). There was no significant difference in HCV RNA load between different groups of patients with HCV genotype 2a (P＞0.05). Of all 36 subjects, 20 reported 34 cases of treatment-emergent adverse events, among which 19 cases were associated with coblopasvir hydrochloride, and no significant adverse events or serious adverse events were observed. ConclusionOral administration of coblopasvir hydrochloride capsules in a fasting state at a dose of 30-120 mg/d (for 3 consecutive days) has good safety and antiviral activity. Therefore, it has good application prospect in the treatment of HCV infection and provides a basis for dose selection in phrase 2 study.

Objective:To analyze the results of the joint screening of newborn hearing and deafness genes in Dalian to provide a reference for the prevention and control of hereditary deafness.Methods:Eight hundred and forty-two neonates born in Dalian Women and Children′s Medical Group from January 1, 2022 to May 30, 2022 were screened retrospectively, using AABR (automatic brainstem evoked potential). And 20 mutation sites of common genetic deafness 4 genes , including GJB2, GJB3, SLC26A4 (PDS) and mitochondrial genes associated with drug-induced deafness (MT-RNRI)(12SrRNA), were detected by high-throughput sequencing.Results:Among the 842 newborns, 840 passed hearing screening (99.8%); 36 cases (4.3%) passed the hearing screening but not the hearing loss gene screening; 804 cases passed through the both screening (95.5%); 2 cases (0.24%) failed in the both screening. 38 cases of deafness gene mutations were detected, with a total carrying rate of 4.51% (38/842). Among them, the carrying rates of heterozygous mutations in GJB2, GJB3, SLC26A4 (PDS), MT-RNRI (12SrRNA) were 1.90%, 0.24%, 1.30%, and 0.95%, respectively. The carrying rates of GJB2/GJB3 composite heterozygous mutations were 0.12%.Conclusions:The combined screening of neonatal hearing and deafness genes can reduce the missed rate of hearing screening. The carrier rate of neonatal deafness gene in Dalian is 4.51%, with the highest GJB 2 carrier rate, followed by SLC26A4 (PDS) carrier rate.

Objective To explore the influence of rs1360780 T risk allele of FK506-binding protein 5 (FKBP5) gene on the brain function under resting-state and its association with clinical symptoms as well as immune function in patients with major depressive disorder (MDD).Methods Totally 147 MDD patients and 61 gender-,age-,and education-matched healthy controls were scanned with 3.0T MRI Scanner and genotyped.The peripheral serum immunoglobulin and complement were measured.The main effect of the disease,the genotype and their interaction effects were analyzed using regional homogeneity (ReHo) by two-way ANOVA.Abnormal brain activity was identified in T risk allele carriers of rs1360780 and non-risk CC individuals in MDD using post hoc analyses.Correlation analyses were performed between ReHo values of significant brain regions and the total score,five-factor scores of Hamilton rating scale for depression (HAMD-17),serum levels of immunoglobulin and plasma complement component in MDD patients.Results (1) The results of 2x 2 ANOVA showed the interaction effects located in the left opercular part of inferior frontal gyrus (MNI:x,y,z =-42,6,9;F=10.83),right opercular part of inferior frontal gyrus (MNI:x,y,z =30,6,33;F=15.05),left medial superior frontal gyrus (MNI:x,y,z=-9,54,0;F=9.17) and left pallidum (MNI:x,y,z =-12,6,-6;F=11.37) (Alphasim corrected,P＜ 0.05).(2) In post-hoc analyses for the main effect of genotype,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=60,12,6;t=2.88) compared with CC carriers;for the effect of diseaseby-genotype interaction,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=30,6,33;t=2.96) and decreased ReHo values in the left orbital part of inferior frontal gyrus (MNI:x,y,z =-21,9,-18;t =-3.21) (Alphasim corrected,P＜ 0.05) in contrast to CC carriers.(3)Pearson's correlation showed that the average ReHo values of the right opercular part of inferior frontal gyrus negatively correlated with the content of immunoglobulin G (r=-0.528,P=O.0016,Bonferroni corrected) and positively correlated with anxiety/somatization factor score (r=0.421,P＜0.001,Bonferroni corrected) in T + carrìers with MDD.Conclusion The results of this study suggest that rs1360780 T-risk allele of FKBP5 gene is involved in the changes of local neural activity in the right opercular part of inferior frontal gyrus of depressed patients and could potentially indicate a neuropathological mechanism of anxiety somatic symptoms and immune dysfunction in depression.

Objective:To explore any effect of supplementing low-frequency repeated transcranial magnetic stimulation (rTMS) with intermittent resistance training on muscle tone and the recovery of motor function among persons with Parkinson′s disease (PD).Methods:A total of 104 PD patients were randomly divided into an observation group and a control group, each of 52. Both groups were treated with conventional drugs and low-frequency rTMS, while the observation group was additionally provided with intermittent resistance training for 8 weeks. Before and after the intervention, the motor functioning of both groups was evaluated using unified Parkinson′s disease rating scale-III (UPDRS-III) and the Berg Balance Scale (BBS). Limb muscle tension was quantified using the modified Ashworth scale (MAS). The subjects′ psychological states were quantified using the exercise self-efficacy scale (ESE), and the modified Barthel index (MBI) was applied to evaluate their ability in the activities of daily living. A 3D motion processing system collected and analyzed data describing each subject′s gait kinematics.Results:After the intervention, significantly greater average improvement was observed in all of the outcome measures among the observation group compared with the control group.Conclusion:Combining intermittent resistance training with low-frequency rTMS can significantly reduce muscle tone and improve the motor functioning of PD patients. The combination is more effective than low-frequency rTMS alone.