Contribution of syphilis to adverse pregnancy outcomes in people living with and without HIV in south Brazil: 2008-2018.

BACKGROUND: Syphilis co-infection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis co-infection on pregnancies in south Brazil. METHODS: Data was extracted from hospital records between 1/1/2008 -12/31/2018. Preterm birth (PTB), low birth weight (LBW < 2500 g), and a composite adverse infant outcome [AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis (LTFU), stillbirth, congenital syphilis] were evaluated among pregnancies without HIV and syphilis (PWOH+S), PLH mono-infection, syphilis mono-infection (PLS), and PLH with syphilis (PLH + S). RESULTS: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1,353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis co-infected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were LTFU. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. 37.0% of PLH + S did not initiate ART versus 15.4% of PLH mono-infection (p < 0.001). 37.6% of PLH + S had VDRL titers > 1:16 compared to 21.7% of PLS only (p < 0.001). Among PLH, syphilis co-infection and unknown/high VDRL titers ( > 1:16) increased AIO risk more (aRR:3.96, 95%CI:3.33-4.70) compared to low VDRL titers ( < 1:8) (aRR:3.51, 95%CI:2.90-4.25). Unsuppressed viremia ( > 50 copies/mL) was associated with risk of PTB (aRR:1.43, 95%CI:1.07-1.92) and AIO (aRR:1.38, 95%CI:1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS mono-infection. CONCLUSION: Syphilis co-infection worsens adverse infant outcomes in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV VL suppression are paramount for optimal obstetric care.

Contraception and Abortion Care for People Living With HIV: A Clinical Guide for Reproductive Health Practitioners.

People capable of pregnancy are disproportionately affected by HIV. Family planning needs and services are often unmet in this population, and clinical care guidelines regarding contraceptive options and abortion care are not well elucidated. Individuals living with HIV often face unique barriers in accessing contraception and abortion services due to internalized stigma, medically complex care (eg, drug-drug interactions, adverse effects of antiretroviral therapy), and distrust of health care providers. There is also a lack of clarity among reproductive health, primary, and infectious disease care providers on best-practice contraceptive counseling and contraceptive care for individuals living with HIV, given limited opportunities to enhance expertise in reproductive infectious disease. In this review, we summarize existing and updated evidence and clinical considerations regarding contraceptive counseling and abortion care in this population.

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018.

BACKGROUND: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. STUDY DESIGN: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. RESULTS: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). CONCLUSION: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

The End Is in Sight: Current Strategies for the Elimination of HIV Vertical Transmission.

PURPOSE OF REVIEW: The goal of this review is to highlight and interpret recent trends and developments in the diagnosis, treatment, and prevention of HIV vertical transmission from a clinical perspective. RECENT FINDINGS: Universal third-trimester retesting and partner testing may better identify incident HIV among pregnant patients and result in early initiation of antiretroviral therapy to prevent vertical transmission. The proven safety and efficacy of integrase inhibitors such as dolutegravir may be particularly useful in suppressing viremia in pregnant persons who present late for ART treatment. Pre-exposure prophylaxis (PrEP) during pregnancy may play a role in preventing HIV acquisition; however, its role in preventing vertical transmission is difficult to elucidate. Substantial progress has been made in recent years to eliminate HIV perinatal transmission. Future research hinges upon a multipronged approach to improving HIV detection, risk-stratified treatment strategies, and prevention of primary HIV infection among pregnant persons.

Risk for adverse maternal outcomes among women with chronic hypertension.

OBJECTIVE: To determine whether longitudinal health data accounts for end-organ injury or death in the setting of chronic hypertension. DESIGN: Cohort of 64 799 deliveries to 61 854 women. SETTING: US claims data for the preiod 2008-2019. POPULATION: Women with a delivery hospitalisation and chronic hypertension. METHODS: Risk for a composite of acute end-organ injury or death during the delivery hospitalisation and 30 days postpartum was analysed. Adjusted logistic regression models were derived with discrimination for each model estimated by the C-statistic. Poisson regression was used to estimate adjusted risk ratios. Starting with models using data from pregnancy, further adjustment was performed accounting for healthcare use in the year prior to pregnancy, including hospitalisations, emergency department encounters, prescription medications and pre-pregnancy diagnoses. MAIN OUTCOME MEASURES: Acute end-organ injury or death. RESULTS: The composite outcome occurred among 5.7% of 64 799 deliveries. For patients with commercial insurance, filling non-hypertensive medications from ≥11 different classes, compared with none (adjusted risk ratio, aRR 4.07, 95% CI 2.86-5.79), three or more hospitalisations before pregnancy, compared with none (aRR 4.75, 95% CI 3.46-6.52), and chronic kidney disease diagnosed in the year before pregnancy (aRR 2.35, 95% CI 1.88, 2.94) were associated with increased risk. For pregnancies covered by commercial insurance, the C-statistic increased from 0.615 (95% CI 0.599-0.630) in the model with pregnancy data only to 0.796 (95% CI 0.783-0.808) for the model additionally including healthcare use in the year before pregnancy. Findings with Medicaid were similar. CONCLUSIONS: Prepregnancy care use predicted adverse maternal outcomes. These data may be important in risk stratification.

Patterns of pregnancy loss among women living with and without HIV in Brazil, 2008-2018.

BACKGROUND: Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. STUDY DESIGN: Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. RESULTS: A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04). CONCLUSION: In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.

Predictors of COVID-19 severity: A literature review.

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors-including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings-that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.

Ubiquitin-specific protease 49 attenuates IL-1ß-induced rat primary chondrocyte apoptosis by facilitating Axin deubiquitination and subsequent Wnt/ß-catenin signaling cascade inhibition.

Osteoarthritis (OA) is an age-related chronic joint degenerative disease. Interleukin 1 beta (IL-1ß) is considered a marker for the progression of OA. In this study, we found that Ubiquitin-Specific Peptidase 49 (USP49) was significantly less expressed in OA patients compared with healthy individuals. Treating primary rat chondrocytes with different concentrations of IL-1ß resulted in decreased Usp49 expression, while Usp49 overexpression could attenuate IL-1ß-induced chondrocyte apoptosis by promoting Axin deubiquitination. The deubiquitination of Axin led to the accumulation of the protein, which in turn resulted in ß-catenin degradation and Wnt/ß-catenin signaling cascade inhibition. Interestingly, we also found that [6]-gingerol, an anti-OA drug, could upregulate the protein level of Usp49 and suppress the Wnt/ß-catenin signaling cascade in primary rat chondrocytes. Taken together, our study not only demonstrates that Usp49 can negatively regulate the progression of OA by inhibiting the Wnt/ß-catenin signaling cascade, but also elucidates the underlying molecular mechanisms.

Evaluation of blood product transfusion therapies in acute injury care in low- and middle-income countries: a systematic review.

BACKGROUND: Worldwide, injuries account for approximately five million mortalities annually, with 90% occurring in low- and middle-income countries (LMICs). Although guidelines characterizing data for blood product transfusion in injury resuscitation have been established for high-income countries (HICs), no such information on use of blood products in LMICs exists. This systematic review evaluated the available literature on the use and associated outcomes of blood product transfusion therapies in LMICs for acute care of patients with injuries. METHODS: A systematic search of PubMed, EMBASE, Global Health, CINAHL and Cochrane databases through November 2018 was performed by a health sciences medical librarian. Prospective and cross-sectional reports of injured patients from LMICs involving data on blood product transfusion therapies were included. Two reviewers identified eligible records (κ=0.92); quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Report elements, patient characteristics, injury information, blood transfusion therapies provided and mortality outcomes were extracted and analyzed. RESULTS: Of 3411 records, 150 full-text reports were reviewed and 17 met inclusion criteria. Identified reports came from the World Health Organization regions of Africa, the Eastern Mediterranean, and South-East Asia. A total of 6535 patients were studied, with the majority from exclusively inpatient hospital settings (52.9%). Data on transfusion therapies demonstrated that packed red blood cells were given to 27.0% of patients, fresh frozen plasma to 13.8%, and unspecified product types to 50.1%. Among patients with blunt and penetrating injuries, 5.8% and 15.7% were treated with blood product transfusions, respectively. Four reports provided data on comparative mortality outcomes, of which two found higher mortality in blood transfusion-treated patients than in untreated patients at 17.4% and 30.4%. The overall quality of evidence was either low (52.9%) or very low (41.2%), with one report of moderate quality by GRADE criteria. CONCLUSION: There is a paucity of high-quality data to inform appropriate use of blood transfusion therapies in LMIC injury care. Studies were geographically limited and did not include sufficient data on types of therapies and specific injury patterns treated. Future research in more diverse LMIC settings with improved data collection methods is needed to inform injury care globally.

A 3D printed porous titanium alloy rod with biogenic lamellar configuration for treatment of the early-stage femoral head osteonecrosis in sheep.

There is no ideal implant for mechanical strut on early-stage osteonecrosis of the femoral head (ONFH) after core decompression. In this study, a biogenic trabecular porous titanium rod with lamellar configuration was designed and fabricated using selective laser melting technique. Early-stage ONFH of sheep induced by cryo-insult were dealt with core decompression combined with rod insertion (Rod group) and core decompression alone (CD group) after X-ray evaluation was used to assess the necrotic region one months after cryo-intervention. Bone integration and ingrowth of the two groups were investigated and compared. Early-stage ONFH intervened with the rod gained better bone ingrowth than CD 3 and 6 months after the intervention, as evidenced by radiographic, micro-CT and histological evaluation. X-ray images showed compact integration between rods and peripheral bone, evidenced by no radiolucent lines encircling the rods at 3 and 6 months. Micro-CT and histological images showed that the new bone had grown into the centre of rods along the metal at 3 months, whereas the new bone grew mainly at the periphery of the decompressive channel. Micro-CT analysis show that the ratios of bone volume to total volume (BV/TV) of volume of interest (VOI) in Rod group was 890.0% and 438.1% higher than CD group at 3 (0.198 ± 0.0094 VS 0.020 ± 0.0058, p < 0.05, n = 3) and 6 (0.226 ± 0.0166 VS 0.042 ± 0.0061, p < 0.05, n = 3) months respectively. Histological analysis showed that the BV/TV of VOI in Rod group was 881.0% and 413.3% higher than CD group at 3 (0.206 ± 0.0102 VS 0.021 ± 0.0061, p < 0.05, n = 3) and 6 (0.231 ± 0.0156 VS 0.045 ± 0.0059, p < 0.05, n = 3) months respectively. The mechanical tests revealed that the maximum load of Rod group was 57.6% larger than CD group at 6 months (4505.25 ± 443.86 N VS 2858.25 ± 512.91 N, p < 0.05, n = 3). These favourable short-term results can provide insight on treatment of early-stage ONFH.

Visual Contrast Sensitivity Correlates to the Retinal Degeneration in Rhodopsin Knockout Mice.

Purpose: Clinical manifestations of photoreceptor degeneration include gradual thinning of the outer nuclear layer (ONL) and progressive reduction of electroretinogram (ERG) amplitudes and vision loss. Although preclinical evaluations of treatment strategies greatly depend on rodent models, the courses of these changes in mice remain unclear. We thus sought to investigate the temporal correlations in changes of spatial vision, ERG response, and ONL thickness in mice with progressive photoreceptor degeneration. Methods: Adult wild-type (WT) mice and mice carrying rhodopsin deficiency (Rho-/-), a frequently used mouse model of human retinitis pigmentosa, were selected for investigation. Mouse spatial vision, including visual acuity (VA) and contrast sensitivity (CS), was determined using optomotor response (OMR) assays; ONL thickness was quantified by spectral-domain optical coherence tomography (SD-OCT), and ERG was performed to evaluate retinal functions. The mice were killed when they were 14 weeks old, and the cone photoreceptors in retinal sections were counted. Results: Spatial vision, ONL thickness, and ERG amplitudes remained stable in WT mice at all examined time points. While 6-week-old Rho-/- mice had VA, CS, as well as ERG responses similar to those of WT mice, progressive reductions in the spatial vision and retinal functions were recorded thereafter. Most tested 12-week-old Rho-/- mice had no visual-evoked OMR and ERG responses. Moreover, CS, but not VA, displayed a linear decline that was closely associated with ONL thinning, reduction of ERG amplitudes, and loss of cones. Conclusions: We presented a comprehensive study of the relation between the changes of spatial vision, retinal function, and ONL thickness in postnatal week (PW)6 to PW12 Rho-/- mice. CS is a more sensitive indicator of spatial vision compared to VA, although both are required as separate parameters for monitoring the visual changes in retina undergoing photoreceptor degeneration.

Author Correction: Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma.

The originally published version of this Article contained an error in Figure 4. The bar chart in panel f was inadvertently replaced with a duplicate of the bar chart in panel e. This error has now corrected in both the PDF and HTML versions of the Article.

Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma.

Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.

Computerized cognitive training for children with neurofibromatosis type 1: A pilot resting-state fMRI study.

In this pilot study, we examined training effects of a computerized working memory program on resting state functional magnetic resonance imaging (fMRI) measures in children with neurofibromatosis type 1 (NF1). We contrasted pre- with post-training resting state fMRI and cognitive measures from 16 participants (nine males; 11.1 ± 2.3 years) with NF1 and documented working memory difficulties. Using non-parametric permutation test inference, we found significant regionally specific differences (family-wise error corrected) in two of four voxel-wise resting state measures: fractional amplitude of low frequency fluctuations (indexing peak-to-trough intensity of spontaneous oscillations) and regional homogeneity (indexing local intrinsic synchrony). Some cognitive task improvement was observed as well. These preliminary findings suggest that regionally specific changes in resting state fMRI indices may be associated with treatment-related cognitive amelioration in NF1. Nevertheless, current results must be interpreted with caution pending independent controlled replication.

Signaling Networks of Retinal Ganglion Cell Formation and the Potential Application of Stem Cell-Based Therapy in Retinal Degenerative Diseases.

Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases.

Targeting osteosarcoma vasculature with peptide obtained by phage display.

AIM OF THE STUDY: Tumour endothelial cells have been proven to have molecular markers distinct from normal endothelial cells. These specific molecular markers allow for targeting of the tumour vasculature with specific pharmacological vehicles to direct diagnostic or therapeutic modalities at the endothelial cells. By performing a phage display-based screening, this study aimed to identify a certain short peptide that could specifically bind to osteosarcoma vasculature. MATERIAL AND METHODS: We performed in vivo screening in the murine models of osteosarcoma with annular Ph.D.-C7C library in the present study. To explore the in vivo binding specificity of the retrieved peptide, we conjugated the peptide with fluorescein isothiocyanate (FITC) and injected it intravenously into osteosarcoma-bearing BALB-c mice. RESULTS: CTKPDKGYC was the dominant sequence isolated from in vivo screening and was named as NF-1. Fluorescence staining found that FITC-NF-1 peptide could be specifically homed to osteosarcoma vasculature while being almost undetectable in the heart, brain, lung and liver. Simultaneously, a small amount of fluorescence could also be detected in the renal glomerulus and renal tubule but not in renal vascular endothelium, indicating that FITC-NF-1 peptide might be excreted mainly through the renal-urinary route. CONCLUSIONS: Our data suggest that, with high binding specificity to osteosarcoma vasculature, peptide NF-1 may have potential value in early diagnosis or targeted therapy for osteosarcoma.

REST corepressor (CoREST) repression induces phenotypic gene regulation in advanced osteoarthritic chondrocytes.

Alternations in cartilage chondrocyte phenotype characteristic by the decreased type II collagen and aggrecan together with increased type X collagen synthesis serve as a beacon for osteoarthritis progression. However, little is known about the underlying molecular mechanisms. The current study seeks to discover molecules that involved in osteoarthritic chondrocytes phenotype regulation. Differential proteomics was generated with two-dimensional gel electrophoresis between normal articular cartilage (NAC) and advanced osteoarthritic cartilage (AOC). Those differentially expressed proteins were identified by mass spectrometry. The down-regulation of a neuronal silencer, the REST corepressor (CoREST) in AOC, was verified by Western blot. CoREST silencing was performed in primarily cultured NAC chondrocytes with specific siRNA to reveal the possible involvement of CoREST repression in chondrocyte phenotypic genes modulation. Ninteen differentially expressed proteins were screened and identified. Among these proteins, CoREST, HHL, and zinc finger protein 155 were estimated to be possible gene modulators. CoREST protein level was verified to be down-regulated by 69.5% (p < 0.001) in AOC. In response to CoREST knock-down by 64.8% (p < 0.001) in NAC chondrocytes, the gene expression level of the chondrocyte terminal differentiation marker gene, collagen X was found to be up-regulated by 40.0% (p = 0.017), whereas the chondrocyte differentiation phenotypic genes, collagen II and aggrecan were down-regulated by 71.4% (p < 0.001) and 57.6% (p < 0.001), respectively. The results indicate that the silencing of CoREST by siRNA transfection in NAC may reflect CoREST repression in AOC, which results in phenotypic genes modulation and suggests a homeostatic role of this transcription factor in articular chondrocyte.

[Comparison of two different methods for establishing nude mouse model bearing osteosarcoma].

OBJECTIVE: To compare two different methods, namely orthotopic implantation and armpit implantation, for establishing nude mouse model bearing osteosarcoma in light of the tumor formation rate and time, tumor growth changes and lung metastasis. METHODS: Osteosarcoma cells were inoculated in the left armpit or the femoral medullary canal of nude mice, and the tumor growth was observed 6 weeks later. The differences in the pulmonary metastasis were examined macroscopically and microscopically. RESULTS: Armpit implantation allowed easy operation and fast tumor growth, but tumors often sustained damages by frictions on the surface (P<0.05), and avascular necrosis occurred earlier in the tumors (P<0.05). With this approach, the pulmonary metastasis rate was only 40% (P<0.05), and the metastases in the lungs were sparser (P<0.05) and small. Orthotopic transplantation could well simulate the original growth environment of osteosarcoma, and resulted in milder avascular necrosis and greater pulmonary metastasis rate (100%) with larger and denser metastatic foci. But orthotopic transplantation required more complicated operation for establishing osteosarcoma-bearing models. CONCLUSION: The two methods both result in high tumor growth rate, but orthotopic transplantation is superior in inducing pulmonary metastasis of osteosarcoma and reducing friction injury of the tumor and avascular necrosis in the tumor.