ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective:To investigate the value of two-dimensional ultrasound combined with shear wave elastography (SWE) in assessing perineal body characteristics in patients with stress urinary incontinence(SUI).Methods:Sixty-four patients with stress urinary incontinence from December 2019 to August 2020 in the Affiliated Hospital of Qingdao University were selected as the SUI group, in addition, seventy healthy females at the same time were selected as the control group. The clinical information data were collected, two-dimensional ultrasound and SWE examination were performed to obtain the perineal body length, height, perimeter, area and the maximum(Emax) and the mean(Emean) modulus of elasticity both at the resting and maximum Valsalva conditions, ROC curve was plotted to evaluate the effectiveness of elastic modulus in evaluating perineal body in SUI.Results:In the resting state, the length, height, perimeter and area of perineal body in the SUI group were not significantly different from those of the control group ( P=0.590, 0.291, 0.082, 0.063). At the maximum Valsalva, the perineal body length, height, perimeter and area in the SUI group were significantly different from those of the control group ( P=0.005, 0.010, 0.001, 0.008). In the resting, the Emax and Emean values of perineal body elastic modulus in the SUI group were higher than those in the control group, but the difference was not statistically significant [(36.61±9.81)kPa vs (34.66±10.38)kPa, (27.43±9.78)kPa vs (26.97±8.85)kPa, all P>0.05]. At the maximum Valsalva, the Emax and Emean of the SUI group were significantly smaller than those of the control group, with statistically significant difference[(47.73±8.03)kPa vs (58.06±10.02)kPa, (35.78±7.89)kPa vs (44.33±9.62)kPa, all P<0.001]. The area under ROC curve of Emax and Emean at the maximum Valsalva was 0.738 and 0.647 respectively, the Emax was better than the Emean in assessment of the characteristics of perineal body in SUI patients. Conclusions:Two-dimensional ultrasound combined with SWE technique can quantitatively evaluate the characteristics of perineal body and provide an important imaging method for the diagnosis of SUI.

Objective To evaluate the combination of transvaginal conventional ultrasonography and shear wave elastography ( SWE) on the diagnosis of endometrial cancer ,and establish a predictive Logistic regression model . Methods Clinical information collection ,transvaginal conventional ultrasonography ,and SWE check were performed in 112 patients w ho were post‐menopausal vaginal bleeding with ≥5 mm thick endometrium . T he Emax and Emean of Young′s modulus for the endometrium were obtained . Pathology was used as the gold standard ,ROC curve was plotted ,which could be used to evaluate the Young′s modulus on the diagnostic effectiveness on endometrial cancer . Single factor analysis and bring logistic regression methods were applied to assess the values of the clinical variables ,transuaginal conventional ultrasonography variables ,and Young′s modulus in the identification of endometrial cancer . Results In 112 cases of endometrial lesions diagnosed by pathology ,there were 84 cases of benign lesions ( benign group) and 28 cases of cancer( malignant group) . Both Emax and Emean in malignant group were larger than benign group [ (53 .00 ± 16 .07) kPa vs ( 31 .99 ± 13 .89) kPa ,( 27 .25 ± 9 .28) kPa vs ( 19 .94 ± 10 .37) kPa ,all P ＜0 .001] . In the logistical regression analysis ,body mass index ,endometrial thickness ,blood flow grading and Young′s modulus were identified as independent risk factors for endometrial cancer . T he accuracy ,sensitivity and specificity of the logistic regression model in the prediction of endometrial cancer were 89 .29% ,82 .14% , and 91 .67% , respectively . T he area under the ROC curve was 0 .928 . Conclusions T ransvaginal conventional ultrasonography combined SWE technique has an important value in the diagnosis of endometrial cancer .

Objective To estimate cervical stiffness during late pregnancy with virtual touch tissue quantification technique(VTQ) and investigate the value of predicting the outcome of labor induction. Methods Cervical length in pregnancy women at 35 -41 weeks′gestation was measured through perineum ultrasound examination before labor induction,and then VTQ was applied to measure shear wave velocity (SWV)values in region of interest(ROI),the maximum,minimum and average of SWV values were obtained from multiple SWV measurement under the VTQ mode. The outcomes of labor induction were tracked and Bishop scores were recorded,vaginal delivery and cesarean delivery groups were compared using Student′s t-test for continuous variables. ROC curve was plotted to analyze the correlation between parameters and the outcome of labor induction and to determine the most accurate SWV value and cut-off value for diagnosis.Univariate and multivariate logistic regression analysis were used to determine which of the following parameters were significant predictors of the outcome of labor induction. Results The SWV mix,SWV max and SWV mean of vaginal delivery and cesarean section were (0.92 ± 0.13)m/s,(1.37 ± 0.14)m/s,(1.13 ± 0.10)m/s and (1.03 ± 0.13)m/s,(1.74 ± 0.42)m/s,(1.36 ± 0.11)m/s,respectively, there were significant differences between vaginal delivery and cesarean section(all P < 0.05).Based on ROC curve analysis,the SWV mean value in cervix was the best value for predicting the outcome of labor induction.The cut-off value of SWV mean value was 1.23 m/s,the sensitivity,specificity and Youden index were 93.8%,83.4%,0.77,respectively.The SWV value and cervical length were closely correlated to the outcome of labor induction,especially the SWV value according to multivariate logistic analysis. Conclusions VTQ can assess the cervical stiffness with SWV values during pregnancy,and it may have an application value of predicting the outcome of labor induction.

Objective To explore the correlation between quantitative parameters of blood perfusion with contrast-enhanced ultrasound (CEUS) and microvessel density (MVD),microvessel area (MVA) in papillary thyroid carcinoma (PTC).And to investigate the value of CEUS in evaluating the angiogenesis in PTC before operation.Methods Totally 69 cases of patients with papillary thyroid carcinoma were selected from April 2014 to October 2016 in the Affiliated Hospital of Qingdao University.The CEUS characteristics of 69 patients with papillary thyroid carcinoma confirmed by pathology were retrospectively analyzed.The patients were divided into three groups according to maximum diameter of lesions (＜ 1 cm group,1-2 cm group and ＞ 2.0 cm group),and two groups according to pathologic reports (neck lymph node metastatic and nonmetastatic groups).The blood perfusion parameters between or among different groups were evaluated by ttest or one-way ANOVA.Immunohistochemical staining were performed to evaluate the MVD,MVA in the surgical specimens,and the correlation of quantitative parameters with MVD,MVA were assessed by Spearman.Results (1) Peak Intensity (Peak),area under the curve (AUC),MVD and MVA of thyroid carcinoma were lower than the surrounding normal thyroid tissue (14.95 ± 4.96 vs 22.67±6.11,970.01±263.20 vs 1798.35±563.67,118.91±31.32 vs 206.27±39.58,8.58±-2.68 vs 18.47±3.13),and the differences were statistically significant (t=-8.700,-11.061,-14.377 and-20.532,all P ＜ 0.05).(2)With the increase of the lesion's maximum diameter,Peak,AUC,MVD and MVA increased,and the differences were statistically significant (t=0.000,0.000,0.000,0.000;t=0.027,0.044,0.033,0.000;t=0.027,0.044,0.033,0.000,all P ＜ 0.05).(3) Papillary thyroid carcinoma with lymphatic involvement had significantly higher values of Peak,AUC,MVD and MVA than those without lymphatic involvement (16.86±4.36 vs 13.80±3.55,1128.16±290.85 vs 874.39±192.27,114.12±30.69 vs 103.67±22.19,10.30 ± 2.44 vs 7.54 ± 2.29),and the differences were statistically significant (t=3.177,4.366,6.336 and 4.742,all P ＜ 0.05).(4) A positive correlation existed between the Peak,AUC and MVD,and the differences were statistically significant (r=0.506,0.478,all P ＜0.05).Peak,AUC and MVA showed positive correlation,and the differences were statistically significant (r=0.648,0.653,all P ＜ 0.05).TP,MTT and MVD,MVA showed no correlations (all P ＞ 0.05).Conclusions The values of Peak and AUC calculated from CEUS were correlated to MVD and MVA.CEUS may be used to evaluated the angiogenesis of PTC before operation.And CEUS is helpful for prediction of prognosis of PTC.

Objective To evaluate the relationship between characteristics of cervical cancer at contrast-enhanced ultrasound and prognostic factors.Methods Thirty-five patients with pathologically confirmed cervical cancer were enrolled in this retrospective analysis.All the patients accepted contrast-enhanced ultrasound examination before the surgery.Relationships between the characters of contrast-enhanced ultrasound and the expression of ki-67 antigen(cell proliferation marker),tumor diameter,lymph node metastasis and histologic grade were studied.Results (1)Compared to the surrounding normal tissue, the cervical cancer had statistically significant differences in time to peak and peak intensity(P <0.05),the former was shortened,and the latter was increased.(2 )The ratio of perfusion defect and heterogeneous enhancement were significantly higher in tissues,including the ki-67 positive expression tissue,poorly differentiated or larger tumors (≥ 2.0 cm in diameter)(P < 0.05 ).(3 )Compared to the ki-67 negative expression group,time to peak of the ki-67 positive expression group was shorter and the peak intensity was higher,the differences were statistically significant (P < 0.05 ).(4 )The peak intensity of poorly differentiated cervical cancers was significantly higher than that of the other groups (P <0.05).Conclusions Enhancement patterns and parameters of contrast-enhanced ultrasound were associated with prognosis, which may be useful in noninvasive prediction of the patients with cervical cancers.

Ambulatory Care Facilities ; Humans ; Mental Disorders ; diagnosis ; Occupational Medicine ; Referral and Consultation ; Symptom Assessment

Objective To investigate the correlation of single nucleotide polymorphisms( SNP) of rs228648 and rs2890565 in urotensin Ⅱ (UTS2)gene with polycystic ovary syndrome(PCOS). Methods The genotypes of two SNPs in UTS2 gene were determined through polymerase chain reaction Tin-shift genotyping method. 101 Chinese Han families trios in Shandong Province consisting of fathers,mothers,and affected daughters with PCOS and 105 healthy women were recruited. The physiological and biochemical parameters including serum follicular stimulating hormone(FSH),luteinizing hormone( LH),testosterone,fasting plasma glucose,and insulin were also measured. Results The distributions of three genotypes and two alleles of SNP rs228648 in UTS2 gene were similar between PCOS group and control group. The distributions of genotypes of SNP rs2890565 in UTS2 gene differed significantly between PCOS group and control group (P<0. 05). The frequency of A allele of SNP rs2890565 in UTS2 gene was significantly higher in PCOS group than that in control group( P<0.05). Transmission disequilibrium test(TDT) did not show significantly biased transmission of two different alleles from parents to affected daughters at rs228648 locus (P>0. 05) ,but showed an excess transmission of A allele from heterozygous parents to affected offspring at rs2890565 locus (P<0. 05). The carriers with GG genotype of SNP rs228648 had significantly higher HOMA-IR compared to those with AA and AG genotypes. The carriers with AA or AG genotype of SNP rs2890565 had significantly higher fasting plasma glucose and fasting insulin compared to those with GG genotypes. HOMA-IR in cases with AA genotype was significantly higher than that with GG genotype. Conclusions There is no association of SNP rs228648 with PCOS, but exists association with insulin resistance. The genetic polymorphism of UTS2 gene rs2890565 may be associated with PCOS,and the higher frequency of A allele is likely to contribute to PCOS.

OBJECTIVETo evaluate the possibility and efficiency of nanoparticle as a new vector in specific gene transference.

METHODSNanoparticle-DNA complex was prepared with Poly-dl-lactic-co-glycolic acid (PLGA) bearing anti-sense monocyte chemotactic protein-1 (A-MCP-1), a specific expression gene, and the package efficiency, release progress in vitro, and the size of the complex were determined. The possibility of the new vector was evaluated with genomic DNA PCR by transferring gene into cultured smooth muscle cells (SMC), cationic lipids as a control. For study in vivo, jugular vein-to-artery bypass grafting procedures were performed on 20 New Zealand white rabbits, of which 6 grafts were transferred with nanoparticle-A-MCP-1 (200 microg), 6 with A-MCP-1 (200 microg) by cationic liposome, 4 with LNCX plasmid, and 4 as control. Fourteen days after the grafts were harvested, the expression of A-MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blot, and the morphologic evaluation of grafts was performed.

RESULTSThe package efficiency of the nanoparticle-DNA complex was 0.9%, release progress in vitro lasted 2 weeks, and the size ranged from 150 to 300 nm. SMC genomic DNA PCR showed that A-MCP-1 gene could be successfully transfected into cells by nanoparticle. The study in vivo indicated that A-MCP-1 mRNA was expressed in both local gene delivery groups, nanoparticle and liposome, meanwhile, MCP-1 expression in vein grafts was significantly inhibited and neointimal hyperplasia was notably reduced.

CONCLUSIONNanoparticle can act as a vector to transfect specific gene.

Animals ; Chemokine CCL2 ; biosynthesis ; genetics ; DNA, Antisense ; biosynthesis ; genetics ; Drug Carriers ; Gene Expression ; Genetic Therapy ; Genetic Vectors ; Lactic Acid ; Nanotechnology ; Particle Size ; Polyglycolic Acid ; Polymers ; Rabbits ; Transfection