[Effect of corneal e-value on myopia control in children and adolescents with orthokeratology].

Objective: To investigate the influence of corneal e-value on the effectiveness of orthokeratology in controlling myopia in children and adolescents. Methods: A retrospective cohort study was conducted, involving the data from 1 563 myopic patients (1 563 eyes) who underwent orthokeratology at the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine from June 2015 to August 2021 and adhered to lens wear for at least 2 years. The cohort consisted of 737 males and 826 females with an average age of (10.84±2.13) years. Based on corneal e-value parameters obtained from corneal topography, patients were categorized into a low e-value group (n=425) and a high e-value group (n=1 138). Data on gender, age, parental myopia history, and baseline measures such as spherical equivalent (SE), axial length, and corneal e-value were collected. Differences in axial length change and corneal fluorescein staining rates were compared between the two groups at 1 and 2 years after the start of lens wear. A generalized linear mixed model was established with axial length change as the dependent variable to analyze the correlation between axial length change and baseline corneal e-value. Results: The initial age of the 1 563 myopic patients was (10.84±2.13) years, with a baseline SE of (-3.05±1.30) D. After 1 year of lens wear, the axial length change was (0.20±0.19) mm in the low e-value group and (0.24±0.20) mm in the high e-value group. After 2 years, the changes were (0.38±0.25) mm and (0.43±0.27) mm, respectively, with statistically significant differences (all P<0.05). The incidence of corneal staining after 1 year of lens wear was 9.2% (39/425) in the low e-value group and 14.1% (160/1 138) in the high e-value group. After 2 years, the rates were 15.8% (67/425) and 21.8% (248/1 138), respectively, with statistically significant differences (all P<0.05). After adjusting for parental myopia history, age, SE, and baseline axial length, the baseline corneal e-value was positively correlated with axial length change at 1 and 2 years after lens wear (all P<0.05). Conclusions: Corneal e-value is an independent factor influencing the effectiveness of orthokeratology in controlling myopia. A smaller corneal e-value is associated with slower axial length growth after orthokeratology, indicating better control of myopia in treated eyes.

[Analysis of different protein expression levels in peripheral blood circulating tumor cells from patients with diffuse large B-cell lymphoma and their predictive efficiency for recurrence].

Objective: To analyze the expression levels of differentiation cluster 47 (CD47), signal regulatory protein α (SIRP-α), proto-oncogene (MYC) and proliferating cell associated antigen (Ki67) proteins in peripheral blood circulating tumor cells (CTC) from patients with diffuse large B-cell lymphoma and their predictive efficiency for tumor recurrence. Methods: The data of 82 patients with diffuse large B-cell lymphoma who were confirmed by histopathology and were in remission after chemotherapy in the Hematology Department of Linyi People's Hospital from January 2018 to January 2021 were retrospectively analyzed. There were 44 males and 38 females, and aged from 50 to 75 (63.8±4.6) years. The patients were divided into recurrent group (n=36) and non-recurrent group (n=46) according to their recurrence within 1 year after remission. The fasting peripheral venous blood samples (4 ml) from patients in the morning were collected, and the CTC were isolated. The expression levels of CD47, SIRP-α, MYC and Ki67 proteins in CTC were detected by Western blotting. The correlations between CD47 expression level and SIRP-α, MYC and Ki67 expression levels were analyzed by Pearson correlation analysis. The predictive efficiency of CD47, SIRP-α, MYC and Ki67 expression levels on tumor recurrence was evaluated by receiver operating characteristic (ROC) curves, and the areas under the curve (AUC) were calculated. Results: The expression levels of CD47, SIRP-α, MYC and Ki67 in recurrent group were 2.24±0.23, 1.17±0.12, 1.98±0.20 and 2.63±0.27, while those in non-recurrent group were 2.04±0.21, 1.31±0.13, 1.53±0.16 and 2.24±0.25. The expression levels of CD47, MYC and Ki67 in the recurrent group were higher than those in the non-recurrent group, while the expression levels of SIRP-α were lower than those in the non-recurrent group (all P<0.001). In 82 patients, the expression levels of CD47, SIRP-α, MYC and Ki67 were 2.13±0.22, 1.25±0.13, 1.73±0.18 and 2.41±0.26, respectively. The expression level of CD47 was negatively correlated with the expression level of SIRP-α (r=-0.308, P=0.005), but positively correlated with the expression level of MYC and Ki67 (r=0.484 and 0.332, P=0.012 and 0.003). The sensitivity of CD47, SIRP-α, MYC and Ki67 expression levels in predicting recurrence of diffuse large B-cell lymphoma was 66.7%, 72.2%, 72.2% and 66.7%, with the specificity of 67.4%, 71.7%, 67.4% and 71.7%, and AUC (95%CI) of 0.694 (0.582-0.791), 0.693 (0582-0.790), 0.714 (0.603-0.808) and 0.709 (0.598-0.804), respectively. The sensitivity of the combined detection of the above four indicators was 83.3%, with the specificity of 78.3% and the AUC (95%CI) of 0.864 (0.771-0.930), which was higher than those of the individual detection of each indicator (all P<0.05). Conclusions: The expression level of CD47 was negatively correlated with the expression level of SIRP-α, but positively correlated with the expression level of MYC and Ki67. The expression levels of CD47, SIRP-α, MYC and Ki67 have certain predictive value for tumor recurrence in patients with diffuse large B-cell lymphoma, and the predictive efficiency of combined detection is higher than single indicator detection.

[Risk factor assessment and adverse outcome prediction of placenta accreta in pregnant women after cesarean section complicated with placenta previa: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95%CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 (P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 (P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion (P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

[Evaluation of two biomechanical stiffness indexes in the diagnosis of eratoconus and their changes after corneal collagen cross-linking surgery].

Objective: To evaluate the diagnostic efficacy of stress-strain index (SSI) for different stages or degrees of keratoconus and changes of SSI and stiffness parameter A1 (SPA1) after corneal collagen cross-linking (CXL) surgery. Methods: Cross-sectional study and retrospective case series study. Ninety-four patients (113 eyes) diagnosed as clinical keratoconus (CKC) in Qingdao Eye Hospital from July 2019 to August 2021 were enrolled in the CKC group, including 69 males and 25 females, aged (20.82±4.53) years, and further divided into subgroups of mild (35 patients, 36 eyes), moderate (36 patients, 40 eyes) and severe (33 patients, 37 eyes) CKC. Fifty-six unaffected eyes of monocular keratoconus patients were enrolled in the subclinical keratoconus (SKC) group. Ninety-one healthy subjects (91 eyes) were recruited as the control group. All subjects were examined by Pentacam topography and Corvis ST measurements to obtain mean keratometry, maximal keratometry, deformation amplitude (DA) ratio at 2 mm, integrated radius (IR), Ambrósio's relational thickness to the horizontal profile, corneal central thickness, SPA1 and SSI for comparison. Forty-eight CKC patients (65 eyes) underwent CXL surgery, and the above parameters were recorded before and 3, 6 and 12 months after operation. Data were analyzed by the ANOVA test, Kruskal-Wallis H test, paired sample test, receiver operating characteristic curves and Pearson correlation. Results: The value of SPA1 in the SKC group accounted for 85.53% (87.92±12.38 vs. 102.79±11.74; t=-6.614, P<0.001) compared with the control group, but the value of SSI had no difference in the two groups (t=0.105, P=0.916). The value of SPA1 in the CKC group accounted for 52.87% (54.35±14.70 vs. 102.79±11.74; t=25.985, P<0.001) compared with the control group. The value of SSI in the CKC group accounted for 67.96% (0.70±0.14 vs. 1.03±0.14; t=-15.305, P<0.001) compared with the control group. The more severe the disease was, the smaller the SPA1 and SSI values were 64.27±12.12, 55.22±12.23, 43.75±12.33; 0.78±0.14, 0.71±0.11, 0.61±0.09, and there were significant statistical differences among groups (mild vs. moderate, mild vs. severe, moderate vs. severe; SPA1: t=3.257, -7.249, -4.159; all P<0.001. SSI: t=2.383, 5.065, 2.798; P=0.018,<0.001,=0.006). Receiver operating characteristic analysis showed that SPA1 had good diagnostic efficiency for subclinical patients [area under curve (AUC)=0.802], while the SSI had no diagnostic value (P=0.802). SPA1 had better diagnostic efficiency than the SSI for keratoconus in different stages, especially in the mild CKC and SKC groups (AUC: 0.914 vs. 0.847). The SSI had a significant positive correlation with SPA1 and a significant negative correlation with DA ratio and IR in the control, SKC and CKC groups (r=0.278, 0.368, 0.550; r=-0.346, -0.462, -0.547; r=-0.612, -0.591, -0.718; P<0.01). For patients who received CXL, maximal keratometry decreased significantly at 6 and 12 months postoperatively (t=4.029, 3.633; all P<0.001), whereas SPA1 increased significantly (t=-3.960, -4.500; all P<0.001). However, the SSI only increased significantly at 3 months (t=-2.577, P=0.012) and returned to the preoperative level at 6 and 12 months postoperatively, with no statistical difference compared with the preoperative level (t=-0.544, -0.257; P=0.589, 0.798). Conclusions: While there was no significant change in the SSI of SKC, the SSI of CKC decreased, and the more severe the disease was, the smaller the value was. The SSI was significantly and consistently correlated with DA ratio, IR and SPA1. The SSI compared with SPA1 had a lower degree of identification in different stages and degrees of keratoconus. The consistency of SPA1 with clinical effects after CXL surgery was higher than that of the SSI parameter.

[Application of latent class model in genetic association between ARID1A low-frequency variants and primary liver cancer].

Objective: To analyze the association between low-frequency variants of ARID1A gene and primary liver cancer using latent category model. Methods: The low-frequency variants of ARID1A gene was combined according to different functional areas, and the combined variables were analyzed by using the latent class model to obtain the latent variables. Then the logistic regression was used to analyze the association between low-frequency variants of ARID1A gene and primary liver cancer. Results: The low-frequency variants of ARID1A gene were divided into three categories by the latent class model. The class 1 was mainly unmutated population, the proportion was 94.2% (2 454/2 603). The class 2 was mainly transcriptional regulatory domain mutation, take 4.8% (124/2 603). The class 3 was dominantly exon mutation, about 1.0% (27/2 603). Using class 1 as a reference, it was found that mutations in the transcriptional regulatory domain could reduce the risk of liver cancer (OR=0.601, 95% CI=0.364-0.992, P=0.046). Conclusion: The latent class model can identify low-frequency variants of gene associated with liver cancer and can be extended to more genetic association studies of low-frequency variants related to complex diseases.

[Evaluation of the diagnosis and treatment of cesarean scar pregnancy induced in the second trimester: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

[The effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator flap breast reconstruction].

Objective: To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. Methods: Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast surgery, Fudan University shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results: The controll groups showed higher aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ²=15.079,P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions: Correlation was observed between adiuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.

Identification of potential mechanosensitive ion channels involved in texture discrimination during Drosophila suzukii egg-laying behaviour.

Drosophila suzukii (spotted wing drosophila) has become a major invasive insect pest of soft fruits in the America and Europe, causing severe yield losses every year. The female D. suzukii shows the oviposition preference for ripening or ripe fruit by cutting the hard skin with its serrated ovipositor. A recent study reported that mechanosensation is involved in the texture discrimination during egg-laying behaviour in D. suzukii. However, the underlying mechanism and molecular entity that control this behaviour are not known. The transient receptor potential (TRP) channels and degenerin/epithelial sodium channels (DEG/ENaC) are two candidate gene families of mechanically activated ion channels. Thus, we first identified TRP and DEG/ENaC genes in D. suzukii by bioinformatic analysis. Using transcriptome sequencing, we found that many TRP genes were expressed in the ovipositor in both D. suzukii and D. melanogaster, while some DEG/ENaCs showed species-specific expression patterns. Exposure to drugs targeting TRP and DEG/ENaC channels abolished the oviposition preference for harder texture in female D. suzukii. Therefore, mechanosensitive ion channels may play significant roles in the texture assessment of egg-laying behaviour in D. suzukii, which has promising implications to further research on the development of novel control measures.

TRIIODOTHYRONINE ACTIVATES GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 3 VIA AGGTCA-LIKE-DIRECT-REPEAT-4 TYPE THYROID HORMONE RESPONSE ELEMENT.

BACKGROUND: Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. METHOD: Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). RESULTS: After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol-3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)-like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. CONCLUSION: Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

Functional integrity of honeybee (Apis mellifera L.) resistant to dieldrin γ-aminobutyric acid receptor channels conjugated with three fluorescent proteins.

To generate an efficient tool used in Xenopus oocyte expression for in situ investigation of channel receptor expression, distribution and function, the C-terminus of the honeybee (Apis mellifera L.) resistant to dieldrin (RDL) subunit was fused with *FP, including monomeric red, enhanced yellow or enhanced green fluorescent protein (referred to as mRFP, EYFP and EGFP, respectively). In the present study, all fused *FP-AmRDLs could be visualized using fluorescence and laser confocal microscopy in cRNA-injected oocytes. Fluorescence was distributed isotropically in the cellular membrane. The potencies of the agonist γ-aminobutyric acid (GABA), but not ß-alanine, and the test antagonists (fipronil, flufiprole, dieldrin, α-endosulfan, bifenazate and avermectin B1a) in the *FP-AmRDL receptor did not significantly differ from that of the untagged receptor with two-electrode voltage clamp detection. The half maximal effective concentrations (EC50 s) of GABA in AmRDL, EGFP-AmRDL, EYFP-AmRDL and mRFP-AmRDL receptors were 11.98, 12.61, 18.92 and 22.11 µM, respectively, and those of ß-alanine were 651.6, 629.6, 1643.0 and 2146.0 µM, respectively. Inhibition percentages of test antagonists against *FP-AmRDL and AmRDL were not significantly different from each other. Overall, the consistency in functional properties between *FP-AmRDL and AmRDL receptors makes pGH19-*FP a promising tool for further in situ investigation of GABA receptors.

[Incidence and yrend of occupational pneumoconiosis in Ankang city from 1974 to 2017].

Objective: To understand the epidemiological feature and prevalent trend of pneumoconiosis in Ankang City, pertinently put forward the prevention and control strategy, and provide the basis for comprehensive prevention and treatment of pneumoconiosis. Methods: China Information System for Disease Control and Prevention has exported the network report data of "occupational diseases and occupational health information monitoring" from January 1, 2006 to December 312017 and has created the database; has investigated and supplemented the occupational disease reporting results from January 1, 1974 to December 31, 2005; has conducted the data cleansing through SPSS17.00; has conducted the statistical description and analysis according to pneumoconiosis diagnosis time, age, sex, length of service, industry, and etc. Results: From 1974 to 2017, Ankang City has accumulatively reported 1047 cases of various occupational pneumoconiosis; of which, 992 new cases and 55 stage development cases. Entities of pneumoconiosis include silicosis, coal workers pneumoconiosis, electric arc welders pneumoconiosis, cement pneumoconiosis and asbestosis; number of new cases of silicosis ranks first, the second is coal workers pneumoconiosis. Average length of employment of the occurrence of pneumoconiosis is (15.01±8.95) years; average length of age of the occurrence is (47.11±7.86) years. Distribution of pneumoconiosis involves 8 industries; the first is mining industry (54.23%) , the second is construction industry (27.52%) , and the third is public management, social security and social organization (12.70%) . Pneumoconiosis involves 24 types of work; the first is drillman (47.28%) , the second is main coal miners (15.52%) , and the third is blasters (13.31%) . Conclusion: Prevention and treatment of pneumoconiosis in Ankang City gives priority to silicosis and coal workers pneumoconiosis, puts emphasis on strengthening the prevention of pneumoconiosis of drillman in the mining industry; the occurrence of pneumoconiosis is in a linear upward trend from 2012.

Parathyroid hormone (1-34) promotes fracture healing in ovariectomized rats with type 2 diabetes mellitus.

Ovariectomized (OVX) rats with type 2 diabetes mellitus (T2DM) with femur fracture received vehicle, insulin, or insulin plus parathyroid hormone (PTH) treatment for 2 and 3 weeks. Radiography, histomorphometry, histology, and immunohistochemistry in callus were evaluated. INTRODUCTION: Reports about effects of PTH plus insulin on callus formation of osteoporotic fracture with T2DM were limited. This study was designed to investigate the effects of the combination of PTH and insulin on fracture healing in OVX rats with T2DM. METHODS: Two-month-old female rats were randomly divided into five groups: normal fracture (F), OVX fracture (OF), T2DM + OVX fracture (DOF), insulin-treated (2-4 u/daylight, 4-6 u/night, DOFI), and treated with insulin and PTH (50 µg/kg/day, 5 days/week, DOFIP). A closed mid-shaft fracture was established in the right femurs of all rats after 6 weeks of OVX. Rats were euthanized at 2 and 3 weeks post-fracture according to the time schedule, respectively. RESULTS: The administration of insulin alone or insulin combined with PTH significantly increased mineralized bone volume fraction (BV/TV) and connectivity density (Conn.D) compared with those of the DOF group at 3 weeks post-fracture and also increased cartilaginous callus area ratio in the DOFI and DOFIP groups at 2 weeks and bony callus area ratio in the DOFIP groups at both the 2 and 3 weeks post-fracture. CONCLUSIONS: OVX rats with T2DM exhibited a marked delay in the fracture healing process; insulin treatment ameliorated these effects, and the healing process was enhanced following treatment with a combination of insulin and PTH.

First report of the qnrA determinant in Shigella sonnei isolated from China.

We investigated the first presence of qnrA among Shigella sonnei clinical isolates in Jiangsu Province, China. The qnrA-positive isolates coexisted with the mutation in gyrA at codon 83, these isolates were resistant to nalidixic acid and 22·2% (2 of 9) of them were resistant to norfloxacin.

[Effect of allogenic mesenchymal stem cells transplantation on the expression of interleukin-22 and matrix metalloproteinase-3 in rats with collagen induced arthritis].

Objective: To study the effect of allogeneic bone marrow mesenchymal stem cells transplantation on the expression of interleukin -22 (IL-22), matrix metalloproteinase -3 (MMP-3) in serum and synovial of rats with collagen induced arthritis. Methods: Type Ⅱ collagen were injected twice to establish the collagen induced arthritis (CIA) rat model. Forty-eight rats were randomly divided into 3 groups: control group, CIA control group, CIA experiment group. Rat bone marrow mesenchymal stem cells were cultured by bone marrow method combined with adherent culture method. After identify, the remaining cells were injected in the CIA experimental group. Enzyme linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of IL-22 and MMP-3 in serum and anklebone joint's synovium of rats, respectively. Synovial cells were isolated and cultured, and were treated with different concentrations of IL-22. MMP-3 protein and mRNA were detected before and after stimulation by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results: After MSC transplantation, arthritis index, X-ray, HE staining of CIA rat showed that joint damage significantly reduced compared with the control group. The ELISA results showed that the expression of MMP-3 and IL-22 in CIA control group was higher than those in the control group (125.79±9.12 vs 102.00±7.63 ng/ml, P<0.05), (292.35±31.23 vs 257.27±13.99 ng/ml, P<0.05) and CIA experiment group (125.79±9.12 vs 97.94±9.50 ng/ml, P<0.05), (292.35±31.23 vs 262.16±22.02 ng/ml, P<0.05) with statistically significant difference (P<0.05). There was no significant difference between the control group and CIA experimental group. Immunohistochemical showed similar results with ELISA. Western blotting and RT-qPCR showed that MMP-3 protein and mRNA expression was increased after IL-22 stimulation in a dose-dependent manner. Conclusion: IL-22 and MMP-3 play an important role in the pathogenesis of rheumatoid arthritis. IL-22 could regulate the expression of MMP-3, and bone marrow mesenchymal stem cells could reduce the expression of MMP-3 in the treatment of rheumatoid arthritis by reducing the expression of IL-22.

Receptor for advanced glycation end-products (RAGE) is overexpressed in human osteosarcoma and promotes the proliferation of osteosarcoma U-2OS cells in vitro.

Osteosarcoma (OS) is an aggressive cancer of the long bones, and usually affects children and young adults. The receptor for advanced glycation end-products (RAGE) has recently been recognized as an oncogenic receptor that binds to different ligands, and promotes the progression of various cancers. However, little is known about the association between RAGE and the pathogenesis of OS. In this study, we first examined the expression of RAGE in OS tissues using immunohistochemical staining, western blotting, and reverse transcription quantitative polymerase chain reaction. We then determined the influence of the overexpressed RAGE on the proliferation of U-2OS cells in vitro. The results showed that RAGE was overexpressed in OS tissues compared with peritumor tissues, at both the mRNA and protein levels, and there was a significant association between overexpressed RAGE and clinicopathological characteristics, such as clinical stage and distant metastasis. Moreover, the overexpression of RAGE in U-2OS cells significantly promoted their proliferation in vitro. In conclusion, this study indicated that RAGE is overexpressed in OS tissue and promotes the proliferation of U-2OS cells. These data imply that RAGE promotes the growth of OS, and is a potential diagnostic biomarker and therapeutic target for the disorder.

[Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice].

OBJECTIVE: To investigate the expression of Jagged1 in human epithelial ovarian carcinoma tissues and the effect of Jagged1 on growth of xenograft in nude mice. METHODS: (1) Forty-eight cases of ovarian cancer and 30 cases of patients with benign epithelial ovarian tumor in the Henan Province Xinxiang Central Hospital during Feb. 2011 to Mar. 2014 were enrolled in this study. The mRNA expression of Jagged1, Notch1 and the downstream target genes Hes1, Hey1 were analyzed by using realtime PCR method. (2) The ovarian cancer xenograft models in nude mice were constructed by injecting SKOV3 cells in axillary subcutaneouswere. The nude mice were randomly divided into Jagged1 interference group, blank plasmid group and control group. Each group had 10 mice. They were transfected with pcDNA3.1(+)-siRNA-Jagged1, blank plasmid pDC3.1 and phosphate buffer, respectively. The tumor volumes and tumor masses were measured 14 days after transfection and the inhibition rate was calculated. The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues after transfection in each group was detected by using realtime PCR technique and the relative protein expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues was detected by utilizing western blot method. RESULTS: (1) The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in ovarian cancer tissues were higher than benign ovarian tumor tissues, the differences were statistically significant (P<0.01). (2) The tumor volume was (491± 68) mm(3) and tumor mass was (2.6±0.4) g in Jagged1 interference group, which were significantly lower than that in the blank plasmid group [(842±88) mm(3) and (4.4±0.8) g, respectively] and that in the control group [(851±90) mm(3) and (4.5±0.9) g, respectively; P<0.05], the tumor inhibition rate was 42.2% in Jagged1 interference group, which was significantly higher than that in the blank plasmid group and that in the control group (2.2% and 0, respectively), the differences were statistically significant (P<0.05). The relative mRNA and protein expression of Jagged1, Hes1 and Hey1 in xenograft tissues of nude micein Jagged1 interference group were lower than that in the other two groups, the differences were statistically significant (P<0.05). There were no differences of relative mRNA and protein expression of Notch1 in xenograft tissues of nude mice among the three groups (P>0.05). CONCLUSIONS: Jagged1 is highly expressed in epithelial ovarian carcinoma. Jagged1 gene interference in xenograft tumor can inhibit ovarian cancer cell growth and improve tumor suppressor rate, which probably play roles by inhibiting Notch1 signaling pathway.

Retinal nerve fiber layer and macular thinning in systemic lupus erythematosus: an optical coherence tomography study comparing SLE and neuropsychiatric SLE.

OBJECTIVE: Due to the lack of reliable biomarkers in diagnosing and monitoring neuropsychiatric systemic lupus erythematosus (NPSLE), the aim of this study was to examine the utility of measurements obtained through spectral domain optical coherence tomography (SD-OCT) as a biomarker for NP involvement in SLE. METHODS: Retinal nerve fiber layer (RNFL) and macula scans were performed using SD-OCT on 15 NPSLE patients, 16 SLE patients without NP symptoms (non-NP SLE), and 16 healthy controls. Macular volume and thickness of the central macula and peripapillary RNFL were compared between the groups and to scores on two validated cognitive tests. RESULTS: NPSLE patients did not differ significantly from non-NP SLE patients in retinal thickness or macular volume. However, SLE patients as a whole showed significant RNFL and macular thinning compared to controls. Scores on the Trail Making Test B, a test of complex attention, showed significant correlation to temporal superior and temporal inferior RNFL thickness. CONCLUSION: Our results demonstrate RNFL thinning in SLE, and confirm the previous finding of high incidence of abnormal brain scans in SLE. These findings suggest that OCT measurements may be indicative of neurodegeneration in SLE and may be a useful biomarker for early cognitive impairment in SLE.

Clinical research of persimmon leaf extract and ginkgo biloba extract in the treatment of vertebrobasilar insufficiency.

This paper aims to compare the curative effects of persimmon leaf extract and ginkgo biloba extract in the treatment of headache and dizziness caused by vertebrobasilar insufficiency. Sixty patients were observed, who underwent therapy with persimmon leaf extract and ginkgo biloba extract based on the treatment of nimodipine and aspirin. After 30 days, 30 patients treated with persimmon leaf extract and 30 patients with ginkgo biloba extract were examined for changes in hemodynamic indexes and symptoms, such as headache and dizziness. The results showed statistically significant differences of 88.3% for the persimmon leaf extract and 73.1% for the ginkgo biloba extract, P < 0.05. Compared to the group of ginkgo biloba extract, the group of persimmon leaf extract had more apparent improvement in the whole blood viscosity, plasma viscosity, fibrinogen, hematokrit, and platelet adhesion rate, and the difference was statistically significant (P < 0.05 or P < 0.01). Based on these analyses, it can be concluded that persimmon leaf extract is better than ginkgo biloba extract in many aspects, such as cerebral circulation improvement, cerebral vascular expansion, hypercoagulable state lowering and vertebrobasilar insufficiency-induced headache and dizziness relief.

Polymorphisms in the SIRT5 gene and their association with body measurement and ultrasound traits in Qinchuan cattle.

Silent information regulator 5 (SIRT5), a member of the Sirtuin family class III nicotinamide adenine dinucleotide-dependent protein deacetylases, plays an important role in metabolic and aging processes in mammals. We identified 4 single-nucleotide polymorphisms (SNPs) (G22010A, G22052A, G22119T, and G22245C) in the 3' untranslated regions of the SIRT5 gene from 572 Qinchuan cattle by sequencing and investigating their association with growth and ultrasound traits. The frequencies of genotype GG and allele G were high at the 4 SNPs. Based on the X(2) test, the genotypic distributions of the 4 SNPs were not in Hardy-Weinberg equilibrium (P < 0.05 or P < 0.01). Association analysis of individual SNPs and haplotype combinations revealed that the 4 loci were significantly associated with some body measurement and ultrasound traits in Qinchuan cattle, and the H1H5 (AG-GA-GG-GG) diplotypes had better performance than other combinations in Qinchuan cattle. Our results demonstrate that SIRT5 may be a candidate for marker-assisted selection in future breeding programs for Qinchuan cattle.