Clinical value of GRACE score combined with DFR in predicting short-term prognosis of patients undergoing early PCI after thrombolysis for acute myocardial infarction.

OBJECTIVE: The aim of the study was to investigate the clinical value of the Global Registry of Arterial Events in Acute Coronary Syndromes (GRACE) score combined with the D-dimer/fibrinogen ratio (DFR) in predicting the short-term prognosis of patients undergoing percutaneous coronary intervention (PCI) early after thrombolysis for acute myocardial infarction (AMI). PATIENTS AND METHODS: A total of 102 patients who underwent PCI early after thrombolysis for AMI during April 2020 to January 2022 in our hospital were picked as study subjects. These subjects were assigned as the good prognosis group (without adverse cardiovascular events) and poor prognosis group (with adverse cardiovascular events) according to whether adverse cardiovascular events occurred during hospitalization and follow-up. Changes in GRACE scores and DFR levels in patients with different prognoses were analyzed. The GRACE score and DFR level of patients with different prognosis were analyzed. The clinic pathological characteristics were collected, and the risk factors for poor prognosis of AMI patients were analyzed by logistic risk regression; ROC curve was used to analyze the prognostic value of GRACE score combined with DFR in early PCI patients after AMI thrombolysis. RESULTS: Compared with the good prognosis group, the GRACE score and DFR level in the poor prognosis group were much higher (p<0.001). Significant differences existed in blood pressure, ejection fraction, number of diseased branches, and Killip grading between the patients with good prognosis and those with poor prognosis (p<0.05). There existed no significant difference in clinical medication between the patients with good prognosis and those with poor prognosis (p>0.05). Logistic multivariate analysis indicated that GRACE score, DFR, ejection fraction, number of lesion branches, and Killip grade were all risk factors influencing the prognosis of patients undergoing early PCI after thrombolysis in AMI (p<0.05). The ROC curve was established and the area under the curve (AUC) of GRACE score, DFR, and combined detection were 0.815, 0.783, and 0.894, respectively, and the sensitivity and specificity were 80.24%, 60.42%, 83.71%, 66.78%, 91.42% and 77.83%, respectively. The AUC, sensitivity, and specificity of combined detection were higher than those of the two alone and had a higher predictive value for the short-term prognosis of patients. CONCLUSIONS: The GRACE score combined with DFR was of great value in diagnosing the short-term prognosis of patients undergoing PCI early after thrombolysis for AMI. Furthermore, the GRACE score, DFR, ejection fraction, number of lesion branches, and Killip classification were all important factors influencing the short-term prognosis of patients, which were of great significance in determining the prognosis of patients.

[Diagnostic value of rapid antigen testing for the detection of SARS-CoV-2 infection].

Objective: To investigate the diagnostic value of rapid antigen test based on colloidal gold immunochromatographic assay for the detection of SARS-CoV-2 infection in symptomatic patients. Methods: From May 20 to June 5 2022, 76 hospitalized children and their 55 accompanying family members with confirmed SARS-CoV-2 infection in the COVID-19 isolation unit of the Children's Hospital of Fudan University (designated referral hospital for SARS-CoV-2 infection in Shanghai) enrolled. Their nasopharyngeal swab specimens were consecutively collected. The samples were tested for SARS-CoV-2 nucleic acid by real-time quantitative. SARS-CoV-2 antigen was tested by immunochromatography. The correlation between the antigen detection results and the change of the cycle threshold (Ct) values were evaluated, as well as the sensitivity and specificity of SARS-CoV-2 antigen detection at different periods after the onset of the disease. Kappa consistency test was conducted to investigate the consistency between the 2 diagnostic methods. Results: Of the enrolled SARS-CoV-2 symptomatic infections, 76 were children, including 41 males and 35 females, with an age of 5 (2, 9) years; 55 were accompanying families, including 8 males and 47 females, with an age of 38 (32, 41) years. All 478 samples were simultaneously tested for SARS-CoV-2 antigen and nucleic acid. In any period from disease onset to negative conversion of viral nucleic acid, the overall sensitivity of the rapid antigen test was 48.2% (119/247), the specificity was 98.3% (227/231), and antigen test and nucleic acid test showed moderate consistency (κ=0.46, P<0.05). The sensitivity of antigen test was 100% (82/82) when the Ct value was ≤25. And the sensitivity of antigen test was 8/10, 4/15 and 8.3% (3/36) when the Ct value was 26, 30 and 35, respectively. All antigen tests were negative when Ct value was >35. During the period of 1-2 days, 3-5 days, 6-7 days, 8-10 days and >10 days after onset, the sensitivity and specificity of SARS-CoV-2 antigen test were 5/8 and 5/5, 90.2% (37/41) and 5/5, 88.9% (24/27) and 2/5, 45.0% (36/80) and 94.1% (32/34), 18.7% (17/91) and 98.9% (183/185) respectively. The Ct values of nasopharyngeal swabs were<26 during 2 to 7 days after onset, 28.7±5.0 on day 8, 34.5±2.9 on day 13 and > 35 after 14 days, respectively. Conclusion: SARS-CoV-2 antigen test in the patients with SARS-CoV-2 infection shows acceptable sensitivity and specificity within 7 days after onset of disease, and the sensitivity was positively correlated with viral load and negatively correlated with onset time.

[Management and short-term outcomes of neonates born to mothers infected with SARS-CoV-2 Omicron variant].

Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15th, 2022 to May 30th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38+3±1+3) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30+1 weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 109 vs. 19.6 (15.4, 36.6) × 109/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.

[Mechanical analysis of the impact of the morphology of the iris and ciliary body on the central vault after posterior chamber phakic intraocular lens implantation].

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) µm, (642±255) µm and (613±280) µm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) µm. The vaults declined by (69±98) µm from postoperative 1 week to 3 months and by (52±54) µm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

[A nomogram for predicting lymph node metastasis in early gastric cancer].

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.

[Analysis of influence factors for short-term recurrence of retroperitoneal liposarcoma after complete resection].

Objective: To examine the influence factors of short-term recurrence after complete surgical resection of retroperitoneal liposarcoma. Methods: The clinicopathological data of retroperitoneal liposarcoma at Department of General Surgery, the First Medical Center, People's Liberation Army General Hospital from January 2000 to January 2020 were retrospectively analyzed. There were 60 males and 31 females, aged (52.1±9.9) years (range: 30 to 84 years). Tumor recurrence within 12 months after complete resection was defined as short-term recurrence, and tumor recurrence more than 12 months was defined as non-short-term recurrence. The t test, rank-sum test, χ2 test and Fisher exact test were conducted for inter-group comparison. Logistic regression analysis was used to analyze the independent influence factors for the short-term recurrence of retroperitoneal liposarcoma after complete resection. The Kaplan-Meier curve was used to calculate the recurrence-free survival, and the Log-rank test was adopted for the comparison between the groups. Results: The univariate analysis results showed that irregular tumor morphology, multiple pathological subtypes, pathological scores>3, and multiple primary tumors are influence factors for short-term recurrence after complete resection of retroperitoneal liposarcoma (χ2: 4.422 to 7.773, all P<0.05). Regression analysis of the above risk factors showed that multiple primary tumors was the independent risk factor (OR=2.918, 95%CI: 1.127 to 7.556, P=0.027). In the short-term recurrence group, Kaplan-Meier curve analysis showed that patients with multiple primary tumors had a shorter median recurrence time than patients with unifocal tumor (6 months vs. 9 months, P=0.028). Conclusions: Multiple primary tumor is an independent risk factor for short-term recurrence after complete resection of retroperitoneal liposarcoma. It suggests that the frequency of follow-up after surgery should be increased for such patients.

[Corneal nerve repair and optical density in patients with high myopia after three kinds of corneal refractive surgery].

Objective: To investigate the repair of subepithelial nerve fibers in different areas of the cornea and the difference of corneal transparency 12 months after small incision lenticule extraction (SMILE), femtosecond laser in situ keratomileusis (FS-LASIK) and excimer laser in situ keratomileusis (LASEK) in high myopia. Methods: A cohort study. From June 2018 to October 2019, 30 patients with high myopia (60 eyes) were selected for corneal refractive surgery in the Department of Ophthalmology, Affiliated Hospital of Qingdao University, including 16 females (32 eyes) and 14 males (28 eyes). According to the mode of operation, the patients were divided into the SMILE group (n=10), FS-LASIK group (n=11) and LASEK group (n=9). The repair of subepithelial nerves in different areas of the cornea was observed by laser confocal microscopy 12 months after operation,and the morphological parameters were analyzed by ACCMetrics software. The parameters included corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD) and corneal nerve fiber width. The Pentacam anterior segment analyzer was used to measure the optical density of the cornea in different diameters. The nerve fiber parameters and corneal optical density were compared by random block analysis of variance, and multiple comparisons were performed between groups by the Turkey test. Results: Twelve months after operation, there was no significant difference in the CNFD among the three groups(all P>0.05). The CNBD around the upper corneal incision in the SMILE group, FS-LASIK group and LASEK group was (7.81±7.93), (9.61±7.18) and (21.25±15.55) branches/mm2, respectively. The CTBD was (22.00±16.02), (24.44±11.42) and (54.37±22.13) branches/mm2, respectively. The values in the LASEK group significantly differed from the other two groups (HSD=2.823, -3.010, 3.053, -3.048, P<0.01). The CNFL was (9.19±3.25), (12.88±3.52) and (15.75±2.36) mm/mm2, respectively. The value in the SMILE group was significantly different (HSD=-3.151, -4.418; P<0.0l). The corneal optical density after SMILE was 13.16±0.72 in the 0-6 mm diameter area(HSD=-4.164, -4.489; P<0.01), 16.12±3.18 in the 6-12 mm diameter area(HSD=-3.918, -3.493;P<0.01) and 14.06±1.36 in the total diameter (HSD=-6.031, -5.519;P<0.01), which differed significantly from the other two groups. Conclusions: Twelve months after SMILE for high myopia, the nerve repair around the superior corneal incision is slightly worse than that after FS-LASIK and LASEK, but the nerve repair in other areas has some advantages, and the corneal transparency is better. (Chin J Ophthalmol, 2021, 57:268-276).

MicroRNA-124 inhibits colorectal cancer cell proliferation and suppresses tumor growth by interacting with PLCB1 and regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Colorectal cancer (CRC) is the most common malignancy for cancer-associated death. This study aimed to investigate the effects of microRNA-124 (miR-124) on tumor proliferation of CRC in vivo and in vitro. MATERIALS AND METHODS: MiR-124 mimics were synthesized and transfected into SW620 cells, which were divided into SW620, microRNA-normal control (miR-NC) and miR-124 mimics group. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine miR-124, chemokine (C-C motif) ligand-20 (CCL20), tankyrase-2 (TNKS2), phospholipase Cbeta1 (PLCB1) and Wnt4. Cell counting kit-8 (CCK-8) was employed to evaluate cell proliferation. The interaction between miR-124 and PLCB1 was tested with the Dual-Luciferase assay. Cell cycle, apoptosis and invasion were also evaluated. CRC xenograft mouse model was established and tumor size was measured. Hematoxylin and eosin (HE) was used to examine inflammation. Western blot was utilized to detect Wnt4. RESULTS: MiR-124 was over-expressed in SW620 cells, significantly reduced CCL20 and enhanced TNKS2 compared to that of the miR-NC group (p<0.05). MiR-124 might play roles by initiating PLCB1 expression. MiR-124 significantly decreased cell viability compared to the miR-NC group (p<0.05). MiR-124 regulated cell cycle and markedly induced apoptosis and inhibited cell invasion compared to the miR-NC group (p<0.05). MiR-124 significantly decreased tumor size of CRC models compared to miR-NC mice (p<0.05). MiR-124 remarkably alleviated inflammation of tumor tissues. MiR-124 markedly enhanced Wnt4 expression compared to the miR-NC group (p<0.05). CONCLUSIONS: MiR-124 inhibited tumor cell proliferation in vitro and suppressed tumor growth in vivo by interacting with PLCB1 and regulating the Wnt/ß-catenin signaling pathway.

Detection of serum procalcitonin and hypersensitive C-reactive protein in patients with pneumonia and sepsis.

Sepsis, a systemic inflammatory response syndrome induced by infection, has high rates of morbidity and mortality. Pneumonia is a major cause for sepsis; however, pneumonia complicated by sepsis is a difficult clinical diagnosis. To assess the clinical relevance of serum procalcitonin (PCT) and hypersensitive C-reactive protein (hs-CRP) in early diagnosis of pneumonia complicated by sepsis, 220 patients with pneumonia who were admitted to hospital from July 2015 to July 2016 were enrolled in this study. The patients were divided into non-sepsis (N=82), mild sepsis (N=97), severe sepsis (N=23), and septic shock (N=18) groups. The patients were also divided into a survival group (N=186) and a death group (N=34) according to their prognosis at 2 weeks. The PCT and hs-CRP levels and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) scores of the two groups were evaluated. The PCT level and APACHE-II score showed a progressively increasing tendency in the non-sepsis, mild sepsis, severe sepsis, and septic shock group; the differences between all pairs of groups were significant (P less than 0.05). The hs-CRP level was significantly lower in the non-sepsis group than in the other groups (P less than 0.05), but differences among the other groups were not significant (P>0.05). The areas under the receiver operating characteristic curves of PCT and hs-CRP for diagnosis of pneumonia complicated by mild and severe sepsis were 0.841 and 0.817, respectively. The optimal cut-off points for pneumonia and sepsis were ≥0.5 ng/mL and ≥55 mg/L, respectively; the sensitivity and specificity were 71.42% and 82.13%, and 75.04% and 53.61%, respectively. The sensitivity and specificity of diagnosis based on PCT and hs-CRP were 89.32% and 85.68%, respectively. PCT and hs-CRP are used to assess the severity of pneumonia in combination with sepsis in new-borns, but PCT is more strongly related to the severity of sepsis than is hs-CRP. Detection of PCT in combination with hs-CRP facilitates the early diagnosis of pneumonia and sepsis in new-borns, as well as monitoring of the treatment response and prediction of the prognosis.

Inflammatory factor in donor liver and its effect on recipient myocardial injury after liver transplantation.

OBJECTIVE: To study the inflammatory factors in donor livers and its effect on recipient myocardial injury after liver transplantation recipients. PATIENTS AND METHODS: Eighteen patients who underwent orthotopic liver transplantations between January 2014 and December 2015 in our hospital were selected. A portion of the hepatic venous blood of donor's livers was preserved in heparinized tubes after partial resection. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and the activity of lactate dehydrogenase (LDH) in serum were measured. The concentrations of TNF-α, IL-6, cTnI, and CK-MB, and the activity of LDH in serum from the central venous blood of recipients were measured at several time points. RESULTS: Persistent myocardial injuries were found in five patients, six experienced a transient increase of cardiac markers after surgery and returned to normal levels 24 h after surgery, and the others were normal. The comparison of the levels of inflammatory factors in serum between the five donors and recipients at different stages showed that the levels of myocardial markers of the donor livers which were supplied to the five cardiac injured patients were all significantly higher than those of other donor's livers, while the levels of serum inflammatory factors in recipients showed no changes during the T0-T2 stage but increased significantly during T3-T5 (p < 0.05). The cardiac function after surgery was significantly different from that before surgery and that of the recipients without myocardial injury (p < 0.05). CONCLUSIONS: Blood pressure changes before surgery may affect the levels of inflammatory factors in donor's liver and cause postoperative myocardial injury in recipients. Proper hypotensive therapy for donors before partial liver resection can prevent postoperative myocardial injury in recipients.

[Research progress in metabolic and receptor-like nuclear imaging agents for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) commonly presents with high morbidity and mortality, and early staging diagnosis and timely treatment is pivotal to prolonging patients' survival time. Compared with traditional morphological imaging methods such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), functional imaging methods like single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are playing an increasingly important role in the early diagnosis, efficacy assessment, prognostic evaluation, and treatment planning for HCC, thanks to their higher sensitivity at a molecular level by using various radiopharmaceuticals.

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma.

Hepatoblastoma is the most common liver tumor of early childhood, which is usually characterized by unusual hypervascularity. Recently, long non-coding RNAs (lncRNA) have emerged as gene regulators and prognostic markers in several cancers, including hepatoblastoma. We previously reveal that lnRNA-TUG1 is upregulated in hepatoblastoma specimens by microarray analysis. In this study, we aim to elucidate the biological and clinical significance of TUG1 upregulation in hepatoblastoma. We show that TUG1 is significantly upregulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis. Overall, our findings indicate that TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. TUG1 is a promising therapeutic target for aggressive, recurrent, or metastatic hepatoblastoma.

Knockdown of porcine endogenous retroviruses by RNA interference in Chinese experimental miniature pig fibroblasts.

BACKGROUND: The clinical application of porcine-derived xenotransplants is limited by the potential risk of infection due to the presence of porcine endogenous retrovirus (PERV) in tissues, organs, and cells. The establishment of pig fibroblasts with low PERV expression and without PERV-C can provide a nuclear donor to generate a safer transgenic pig. METHODS: In this study, we obtained Chinese Experimental Miniature Pig fibroblasts (CEMPF) with low expression of PERV and none of PERV-C. We designed small interfering RNA (siRNA) expressed as short hairpin RNAs (shRNA) based on the highly conserved gag and pol regions of PERV and screened for the most effective siRNA to inhibit PERV expression. The selected shRNA-pol3 fragment was introduced into the CEMPF to obtain an engineered CEMPF stably expressing shRNA-pol3. RESULTS: The PERV mRNA expression level in the engineered CEMPF was only 7.9% of that observed in fibroblasts from wild-type CEMPF, PERV P15E protein expression was significantly reduced. HEK293 cells cocultured with the supernate of the engineered CEMPF showed no PERV infection. CONCLUSIONS: Engineered CEMPF, which possess no risk of PERV-A/C infection, can serve as a nuclear donor to generate xenograft donor pigs.

Slow binocular rivalry in bipolar disorder.

BACKGROUND: The rate of binocular rivalry has been reported to be slower in subjects with bipolar disorder than in controls when tested with drifting, vertical and horizontal gratings of high spatial frequency. METHOD: Here we assess the rate of binocular rivalry with stationary, vertical and horizontal gratings of low spatial frequency in 30 subjects with bipolar disorder, 30 age- and sex-matched controls, 18 subjects with schizophrenia and 18 subjects with major depression. Along with rivalry rate, the predominance of each of the rivaling images was assessed, as was the distribution of normalized rivalry intervals. RESULTS: The bipolar group demonstrated significantly slower rivalry than the control, schizophrenia and major depression groups. The schizophrenia and major depression groups did not differ significantly from the control group. Predominance values did not differ according to diagnosis and the distribution of normalized rivalry intervals was well described by a gamma function in all groups. CONCLUSIONS: The results provide further evidence that binocular rivalry is slow in bipolar disorder and demonstrate that rivalry predominance and the distribution of normalized rivalry intervals are not abnormal in bipolar disorder. It is also shown by comparison with previous work, that high strength stimuli more effectively distinguish bipolar from control subjects than low strength stimuli. The data on schizophrenia and major depression suggest the need for large-scale specificity trials. Further study is also required to assess genetic and pathophysiological factors as well as the potential effects of state, medication, and clinical and biological subtypes.

Temporal relationship between the auditory brainstem response and focal responses of auditory nerve root and cochlear nucleus during development in the tammar wallaby (Macropus eugenii).

Thirty-two pouch-young tammar wallabies were used to discover the generators of the auditory brainstem response (ABR) during development by the use of simultaneous ABR and focal brainstem recordings. A click response from the auditory nerve root (ANR) in the wallaby was recorded from postnatal day (PND) 101, when no central auditory station was functional, and coincided with the ABR, a simple positive wave. The response of the cochlear nucleus (CN) was detected from PND 110, when the ABR had developed 1 positive and 1 negative peak. The dominant component of the focal ANR response, the N1 wave, coincided with the first half of the ABR P wave, and that of the focal CN response, the N1 wave, coincided with the later two thirds. In older animals, the ANR response coincided with the ABR's N1 wave, while the CN response coincided with the ABR's P2, N2 and P3 waves, with its contribution to the ABR P2 dominant. The protracted development of the marsupial auditory system which facilitated these correlations makes the tammar wallaby a particularly suitable model.

Functional development of the inferior colliculus (IC) and its relationship with the auditory brainstem response (ABR) in the tammar wallaby (Macropus eugenii).

To discover the developmental relationship between the auditory brainstem response (ABR) and the focal inferior colliculus (IC) response, 32 young tammar wallabies were used, by the application of simultaneous ABR and focal brainstem recordings, in response to acoustic clicks and tone bursts of seven frequencies. The IC of the tammar wallaby undergoes a rapid functional development from postnatal day (PND) 114 to 160. The earliest (PND 114) auditory evoked response was recorded from the rostral IC. With development, more caudal parts of the IC became functional until age about PND 127, when all parts of the IC were responsive to sound. Along a dorsoventral direction, the duration of the IC response decreased, the peak latency shortened, while the amplitude increased, reaching a maximum value at the central IC, then decreased. After PND 160, the best frequency (BF) of the ventral IC was the highest, with values between 12.5 and 16 kHz, the BF of the dorsal IC was the lowest, varying between 3.2 and 6.4 kHz, while the BF of the central IC was between 6.4 and 12.5 kHz. Between PND 114 and 125, the IC response did not have temporal correlation with the ABR. Between PND 140 and 160, only the early components of the responses from the ventral and central IC correlated with the P4 waves of the ABR. After PND 160, responses recorded from different depths of the IC had a temporal correlation with the ABR.