Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model.

Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD) and a major contributor to vision loss in nAMD cases. However, the identification of specific cell types associated with nAMD remains challenging. Herein, we performed single-cell sequencing to comprehensively explore the cellular diversity and understand the foundational components of the retinal pigment epithelium (RPE)/choroid complex. We unveiled 10 distinct cell types within the RPE/choroid complex. Notably, we observed significant heterogeneity within endothelial cells (ECs), fibroblasts, and macrophages, underscoring the intricate nature of the cellular composition in the RPE/choroid complex. Within the EC category, four distinct clusters were identified and EC cluster 0 was tightly associated with choroidal neovascularization. We identified five clusters of fibroblasts actively involved in the pathogenesis of nAMD, influencing fibrotic responses, angiogenic effects, and photoreceptor function. Additionally, three clusters of macrophages were identified, suggesting their potential roles in regulating the progression of nAMD through immunomodulation and inflammation regulation. Through CellChat analysis, we constructed a complex cell-cell communication network, revealing the role of EC clusters in interacting with fibroblasts and macrophages in the context of nAMD. These interactions were found to govern angiogenic effects, fibrotic responses, and inflammatory processes. In summary, this study reveals noteworthy cellular heterogeneity in the RPE/choroid complex and provides valuable insights into the pathogenesis of CNV. These findings will open up potential avenues for deep understanding and targeted therapeutic interventions in nAMD.

Proliferative glomerulonephritis with monoclonal IgG Lambda deposits caused by plasmablastic lymphoma: a case report.

INTRODUCTION: As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. CASE PRESENTATION: We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. CONCLUSION: The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

Canine and murine models of osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor in children. Despite efforts to develop and implement new therapies, patient outcomes have not measurably improved since the 1980s. Metastasis continues to be the main source of patient mortality, with 30% of cases developing metastatic disease within 5 years of diagnosis. Research models are critical in the advancement of cancer research and include a variety of species. For example, xenograft and patient-derived xenograft (PDX) mouse models provide opportunities to study human tumor cells in vivo while transgenic models have offered significant insight into the molecular mechanisms underlying OS development. A growing recognition of naturally occurring cancers in companion species has led to new insights into how veterinary patients can contribute to studies of cancer biology and drug development. The study of canine cases, including the use of diagnostic tissue archives and clinical trials, offers a potential mechanism to further canine and human cancer research. Advancement in the field of OS research requires continued development and appropriate use of animal models. In this review, animal models of OS are described with a focus on the mouse and tumor-bearing pet dog as parallel and complementary models of human OS.

Cancer-related fatigue in hospitalised patients treated for lymphoma and its burden on family caregivers.

OBJECTIVE: To investigate the prevalence of cancer-related fatigue (CRF) in patients with lymphoma and to explore the burden of CRF on the family caregivers (FCs). METHODS: A cross-sectional study was conducted in a university-affiliated tertiary care hospital in China. Patients with lymphoma who received treatment in the in-patient ward of the Haematology Department were consecutively recruited. Face-to-face interviews were conducted to gather information related to the patients' sociodemographic characteristics and perceived CRF and its burden on the FCs. Cochran-Armitage trend analysis and Multivariable logistic regression analyses were employed to determine the association between CRF and the FCs' burden. RESULTS: Of the 116 cancer patient-FC dyads, about 70% of patients experienced some level of fatigue, while 51% of unpaid family members suffered some degree of depression. The Cochran-Armitage trend analysis showed that the FCs' burden significantly increased with the severity of CRF. Logistic regression indicated that the FCs of the patients reporting fatigue experienced a higher burden in both the unadjusted and adjusted models. CONCLUSION: The prevalence of CRF appeared to be high among patients with lymphoma. It might be important to design innovative health-promoting practices for ameliorating or preventing the impact of fatigue.

Study of the Osteoimmunomodulatory Properties of Curcumin-Modified Copper-Bearing Titanium.

Peri-implantitis can lead to implant failure. In this study, curcumin (CUR) was modified onto the copper-bearing titanium alloy (Cu-Ti) with the assistance of polydopamine (PDA) in order to study the bone immune response and subsequent osteogenesis. FE-SEM, XPS and water contact angle were utilized to characterize the coating surface. Bone marrow mesenchymal stem cells (BMSCs) and macrophages were cultured separately and together onto the CUR modified Cu-Ti. Cell activity, expression of relative genes and proteins, cell migration ability, and fluorescence staining of cells were performed. CUR modification slightly increased the activation of M1-type and M2-type cells under physiological conditions. In the inflammation state, CUR inhibited the overexpression of M1 macrophages and induced M2-type differentiation. In addition, the modification itself could provoke the expression of osteoblastic-related genes of BMSCs, while promoting the osteogenic differentiation of BMSCs through the activation of macrophages in both physiological and inflammatory states. The BMSCs migration was increased, the expression of osteogenic-related genes and proteins was up-regulated, and alkaline phosphatase activity (ALP) was increased. Thus, the modification of CUR can promote the osteointegration effect of Cu-Ti by bone immunomodulation and may, in addition, improve the success rate of implants.

[Application of Micro-flow Imaging in the Differentiation of Benign and Malignant Thyroid Nodules].

Objective To evaluate the performance of micro-flow imaging(MFI)in the differential diagnosis of benign and malignant thyroid nodules. Methods Totally 50 patients with thyroid nodules examined by conventional ultrasound,MFI,and contrast-enhanced ultrasound and confirmed by histological or cytological pathology in the First Medical Center of Chinese PLA General Hospital from May to December in 2020 were enrolled in the study.The clinical data and ultrasound images were retrospectively analyzed.A binary logistic regression model was established to evaluate the performance of the model in predicting benign and malignant thyroid nodules. Results Logistic regression showed that composition and "S-W-C" sign were independent risk factors for predicting malignant thyroid nodule.The sensitivity,specificity,and Youden index of the logistic regression model were 73.33%,80.00%,and 0.53,respectively,and the area under receiver operating characteristic curve was 0.799(95%CI=0.662-0.899). Conclusion MFI facilitates the differential diagnosis of benign and malignant thyroid nodules and has the potential to be applied in the future.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Triglyceride-Glukose Index Predicts Adverse Events in Patients with Acute Coronary Syndrome: A Meta-Analysis of Cohort Studies.

The triglyceride-glucose (TyG) index, a recently proposed indicator for insulin resistance, has been related with cardiovascular risks. We aimed to summarize the association between TyG index and incidence of major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Cohort studies demonstrating the association between TyG index and incidence of MACEs in ACS patients with multivariate adjusted analyses were identified by search of PubMed, Embase, and Web of Science databases. A random-effekt model incorporating the heterogeneity was applied to pool the results. Eight cohort studies with 19 611 participants were included. Results showed that compared to those with the lowest category of TyG index, ACS patients with the highest category of TyG index were independently associated with higher risk of MACEs [risk ratio (RR): 1.94, 95% confidence interval (CI): 1.47-2.56, I2=85%, p <0.001). Subgroup analyses showed consistent results in patients with ST-segment elevated myocardial infarction or non-ST segment elevated ACS, in patients with or without diabetes, and in patients after percutaneous coronary intervention. Results were consistent in studies with TyG index analyzed as continuous variable (RR for per standard deviation increment of TyG index: 1.59, 95% CI: 1.38-1.83, I2=24%, p <0.001). In conclusion, higher TyG index may be independently associated with higher incidence of MACEs in patients with ACS.

Radiofrequency ablation versus total thyroidectomy in patients with papillary thyroid microcarcinoma located in the isthmus: a retrospective cohort study.

OBJECTIVE: This retrospective study aimed to examine the benefits and complications of radiofrequency ablation (RFA) in patients with papillary thyroid microcarcinoma (PTMC) in the isthmus. METHODS: This retrospective study included patients with PTMC in the isthmus and treated at the Chinese People's Liberation Army hospital from 05/2014 to 05/2018. The patients were divided into the RFA and total thyroidectomy (TT) groups. The outcomes were operation-related complications, rate of recurrence, metastasis rate, and thyroid carcinoma-specific questionnaire of quality of life (THYCA-QOL). RESULTS: Among 218 patients, 115 patients underwent RFA, and 103 underwent TT. The rates of disappearance of the ablation zone at 1, 3, 6, 12, and 18 months after RFA were 0.8% (1/115), 10.4% (12/115), 51.3% (59/115), 90.4% (104/115), and 100% (115/115), respectively. Surgical time, blood loss, hospital stays, and treatment costs were higher with TT than with RFA (all p < 0.001). The final THYCA-QOL score of the RFA group was significantly higher than in the TT group (p < 0.001). Minor pain at the operation site was seen in all patients in the RFA group. No distant metastasis was detected in all patients, but one patient in the RFA group had a recurrence after 6 months. The final THYCA-QOL score of the RFA group was significantly lower than in the TT group (p < 0.001). CONCLUSION: These results suggest that RFA for PTMC in the isthmus had similar outcomes than TT. It will have to be confirmed in future studies.

Radiofrequency ablation versus reoperation for benign thyroid nodules that developed after previous thyroid surgery.

PURPOSE: To compare the clinical outcomes of radiofrequency ablation (RFA) versus reoperation for benign thyroid nodules that developed after previous thyroid surgery. METHODS: A total of 53 patients with 53 benign nodules developed after previous thyroid surgery were evaluated in this retrospective study. Eighteen patients were treated by RFA (RFA group) and 35 patients underwent reoperation (reoperation group). The efficacy, safety, thyroid function, blood loss, hospitalization, total treatment time, and cost were compared between the two groups. RESULTS: In the RFA group, the mean volume decreased significantly from 12.78 ± 17.57 ml to 0.94 ± 1.01 ml (p = 0.043) with a volume reduction rate of 85.27 ± 14.35% and significant improvement in symptom and cosmetic scores (all p = 0.001). Therapeutic efficacy was achieved with a single session in all thyroid nodules. The total treatment time (6.12 ± 3.17 min vs. 110.26 ± 44.41 min, p < 0.001), blood loss (0 ml vs. 82.58 ± 105.55 ml, p < 0.001) and hospitalization(0 days vs. 9.66 ± 4.28 days, p < 0.001) were significantly lower in the RFA group than those in reoperation group, but the costs of treatment were similar(2262.12 ± 221.54 USD vs. 2638.04 ± 1062.90 USD, p = 0.081). The incidence of complications was significantly higher in the reoperation group than in the RFA group(31.43 vs. 0%, p < 0.001). Furthermorre, 65.17% of patients developed hypothyroidism after reoperation, whereas the thyroid function of the patients in the RFA group was unaffected. CONCLUSION: For patients with benign thyroid nodules developed after previous thyroid surgery, RFA can be considered as a safe and effective alternative to reoperation with advantages of maintenance of intact thyroid function and low incidence of complications.

[Protective effect and mechanism of Wangshi Baochi Pills against acute alcoholic liver/stomach injury in mice].

As a common disease worldwide, alcoholic liver injury is caused by long-term or excessive intake of alcohol and triggers cell death due to alcohol metabolism and reactive oxygen species(ROS)-mediated cytotoxicity. Wangshi Baochi(WSBC) Pills have been widely adopted in clinical practice for evacuating stasis, resolving turbidity, clearing heat, tranquilizing mind, invigorating sto-mach, promoting digestion, purging fire and removing toxin. This study aimed to investigate the efficacy of WSBC Pills in dispelling the effect of alcohol and protecting against acute alcoholic liver/stomach injury in mice, and preliminarily investigate its possible mole-cular mechanism. The results found that the preventive treatment with WSBC Pills contributed to elevating the activity of alcohol dehydrogenase(ADH) and its expression in liver and shortening the time required for sobering up of mice with acute alcoholic liver injury. The staining of liver pathological sections as well as the detection of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and liver ROS levels revealed that WSBC Pills protected the liver by reducing serum AST and ALT. It suppressed oxidative stress-induced liver injury by lowering liver ROS and elevating superoxide dismutase(SOD), and the liver-protecting effect was superior to that of silibinin. Western blot assay confirmed that WSBC Pills inhibited the oxidative stress by up-regulating SOD1 and NAD(P)H: quinone oxidoreductase 1(NQO-1). In addition, WSBC Pills lowered the ROS level to protect against the acute alcoholic stomach injury in mice. The findings have suggested that WSBC Pills alleviated the acute alcoholic liver/stomach injury in mice by increasing ADH and resisting oxidative stress.

Papillary thyroid carcinoma: an ultrasound-based nomogram improves the prediction of lymph node metastases in the central compartment.

OBJECTIVES: To develop a nomogram based on postoperative clinical and ultrasound findings to quantify the probability of central compartment lymph node metastases (CLNM). METHODS: A total of 952 patients with histologically confirmed papillary thyroid carcinoma (PTC) were included in this retrospective study and assigned to three groups based on sex and age. The strongest predictors for CLNM were selected according to ultrasound imaging features, and an ultrasound (US) signature was constructed. By incorporating clinical characteristics, a predictive model presented as a nomogram was developed, and its performance was assessed with respect to calibration, discrimination and clinical usefulness. RESULTS: Predictors contained in the nomogram included US signature, US-reported LN status and age. The US signature was constructed with tumour size and microcalcification. The nomogram showed excellent calibration in the training dataset, with an AUC of 0.826 (95% CI, 0.765-0.887) for male patients, 0.818 (95% CI, 0.746-0.890) for young females and 0.808 (95% CI, 0.757-0.859) for elder females. For male and young female patients, application of the nomogram to the validation cohort revealed good discrimination, with AUCs of 0.813 (95% CI, 0.722-0.904) and 0.814 (95% CI, 0.712-0.915), respectively. Conversely, for elderly female patients, the nomogram failed to show good performance with an AUC of 0.742 (95% CI, 0.661-0.823). CONCLUSION: This ultrasound-based nomogram may serve as a useful clinical tool to provide valuable information for treatment decisions, especially for male and younger female patients. KEY POINTS: • Age, gender, US-reported LN status and US signature were the strongest predictors of CLNM in PTC patients and informed the development of a predictive nomogram. • Microcalcification was the strongest predictor in the US signature, as CLMN was identified in approximately 92% of patients characterised by diffuse microcalcification. • Stratified by sex and age, this nomogram achieved good performance in predicting CLNM, especially in male and young female patients. This prediction tool may be useful as an imaging marker for identifying CLNM preoperatively in PTC patients and as a guide for personalised treatment.

NCAPG Dynamically Coordinates the Myogenesis of Fetal Bovine Tissue by Adjusting Chromatin Accessibility.

NCAPG is a subunit of condensin I that plays a crucial role in chromatin condensation during mitosis. NCAPG has been demonstrated to be associated with farm animal growth traits. However, its role in regulating myoblast differentiation is still unclear. We used myoblasts derived from fetal bovine tissue as an in vitro model and found that NCAPG was expressed during myogenic differentiation in the cytoplasm and nucleus. Silencing NCAPG prolonged the mitosis and impaired the differentiation due to increased myoblast apoptosis. After 1.5 days of differentiation, silencing NCAPG enhanced muscle-specific gene expression. An assay for transposase-accessible chromatin- high throughput sequencing (ATAC-seq) revealed that silencing NCAPG altered chromatin accessibility to activating protein 1 (AP-1) and its subunits. Knocking down the expression of the AP-1 subunits fos-related antigen 2 (FOSL2) or junB proto-oncogene (JUNB) enhanced part of the muscle-specific gene expression. In conclusion, our data provide valuable evidence about NCAPG's function in myogenesis, as well as its potential role in gene expression.

[Application of Ultrasound Model for Predicting Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma].

Objective To establish a predictive model for central compartment lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC).Methods We retrospectively evaluated patients with histologically confirmed PTC treated in Chinese PLA General Hospital between January 2018 and January 2019.Totally 855 patients undergoing thyroidectomy with central lymph node dissection were enrolled in this study (577 in the training cohort and 278 in the validation cohort).The clinical manifestations of the patients and the ultrasound features of the tumors were recorded.To predict the probability of CLNM,we developed the clinical-ultrasound model with significant factors selected by the stepwise logistic regression.The Akaike Information Criterion (AIC) was use to select the optimal model,and the area under the curve (AUC) and the calibration curves were used to evaluate the performance of the prediction model.Results Multivariate analysis showed that sex (P<0.001),age 45-55 years (P=0.004) or ≥55 years (P=0.003),tumor size 1-2 cm (P<0.001) or >2 cm (P=0.008),multifocality (P=0.029),microcalcification (P=0.019),diffused distribution of microcalcifications (P=0.001),and vascularity levels 2-3 (P=0.002) were effective for CLNM prediction.The model based on the clinical and ultrasound features showed good performance in both training cohort with AUC of 0.78 (95%CI:0.74-0.82) and validation cohort with AUC of 0.70 (95%CI:0.67-0.76).Conclusions A quantitative model of CLNM in PTC patients was established based on the risk factors.According to the model,central lymph node dissection is recommended for PTC patients with high scores.

[Quantitative Evaluation of Sciatic Nerve Crush Injury with Conventional Ultrasound Combined with Shear-wave Elastography in Rabbit Models].

Objective To explore the value of conventional ultrasound combined with shear-wave elastography in the quantitative evaluation of sciatic nerve crush injury in rabbit models. Methods Forty healthy male New Zealand white rabbits were randomly divided into four groups (n=10 in each group):three crush injury (CI) groups (2,4,and 8 weeks after crush) and control group (without injury). The thickness and stiffness of the crushed sciatic nerves and denervated triceps surae muscles were measured at different time points and compared with histopathologic parameters. Inter-reader variability was assessed with intraclass correlation coefficients. Results Compared with the control group,the inner diameters of the sciatic nerves significantly increased in the 2-week CI group [(1.65±0.34) mm vs. (0.97±0.15) mm,P=0.00] but recovered to the nearly normal level in the 8-week CI group [(1.12±0.18) mm vs. (0.97±0.15) mm,P=0.06];however,compared with control group [(8.75±1.02)kPa],the elastic modulus of the nerves increased significantly in all the CI groups [2-week:(14.77±2.53) kPa;4-week:(19.12±3.46) kPa;and 8-week:(28.39±5.26) kPa;all P=0.00];pathologically,massive hyperplasia of collagen fibers were found in the nerve tissues. The thickness of denervated triceps surae muscle decreased gradually,and the elastic modulus decreased 2 weeks after injury but increased gradually in the following 6 weeks;pathologically,massive hyperplasia of collagen fibers and adipocytes infiltration were visible,along with decreased muscle wet-weight ratio and muscle fiber cross-sectional area. The inter-reader agreements were good. Conclusion Conventional ultrasound combined with shear-wave elastography is feasible for the quantitative evaluation of the morphological and mechanical properties of crushed nerves and denervated muscles.

Heme oxygenase-1 attenuates the inhibitory effect of bortezomib against the APRIL-NF-κB-CCL3 signaling pathways in multiple myeloma cells: Corelated with bortezomib tolerance in multiple myeloma.

Osteoclasts (OCs) play an essential role in bone destruction in patients with multiple myeloma (MM). Bortezomib can ameliorate bone destruction in patients with MM, but advanced MM often resists bortezomib. We studied the molecular mechanisms of bortezomib tolerance in MM. The expression of the MM-related genes in newly diagnosed patients with MM and normal donors were studied. C-C motif chemokine ligand 3 (CCL3) is a cytokine involved in the differentiation of OCs, and its expression is closely related to APRIL (a proliferation-inducing ligand). We found that bortezomib treatment inhibited APRIL and CCL3. But the heme oxygenase-1 (HO-1) activator hemin attenuated the inhibitory effects of bortezomib on APRIL and CCL3. We induced mononuclear cells to differentiate into OCs, and the enzyme-linked immunosorbent assay showed that the more OCs differentiated, the higher the levels CCL3 secretions detected. Animal experiments showed that hemin promoted MM cell infiltration in mice. The weight and survival rate of tumor mice were associated with HO-1 expression. Immunohistochemical staining showed that HO-1, APRIL, and CCL3 staining were positively stained in the tumor infiltrating sites. Then, MM cells were transfected with L-HO-1/si-HO-1 expression vectors and cultured with an nuclear factor (NF)-kappa B (κB) pathway inhibitor, QNZ. The results showed that HO-1 was the upstream gene of APRIL, NF-κB, and CCL3. We showed that HO-1 could attenuate the inhibitory effect of bortezomib against the APRIL-NF-κB-CCL3 signaling pathways in MM cells, and the tolerance of MM cells to bortezomib and the promotion of bone destruction are related to HO-1.

A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells.

The inactivation of p53 creates a major challenge for inducing apoptosis in cancer cells. An attractive strategy is to identify and subsequently target the survival signals in p53 defective cancer cells. Here we uncover a RUNX2-mediated survival signal in p53 defective cancer cells. The inhibition of this signal induces apoptosis in cancer cells but not non-transformed cells. Using the CRISPR technology, we demonstrate that p53 loss enhances the apoptosis caused by RUNX2 knockdown. Mechanistically, RUNX2 provides the survival signal partially through inducing MYC transcription. Cancer cells have high levels of activating histone marks on the MYC locus and concomitant high MYC expression. RUNX2 knockdown decreases the levels of these histone modifications and the recruitment of the Menin/MLL1 (mixed lineage leukemia 1) complex to the MYC locus. Two inhibitors of the Menin/MLL1 complex induce apoptosis in p53 defective cancer cells. Together, we identify a RUNX2-mediated epigenetic mechanism of the survival of p53 defective cancer cells and provide a proof-of-principle that the inhibition of this epigenetic axis is a promising strategy to kill p53 defective cancer cells.

In vitro study on cytocompatibility and osteogenesis ability of Ti-Cu alloy.

Titanium implants easily suffer bacteria-related infections in clinic due to their inherent lack of self-protection ability. Therefore, a novel Ti-Cu alloy with good antibacterial activity has been developed as a new kind of implant material. This study focuses on a systematic evaluation of both cytocompatibility and osteogenesis activity of the Ti-Cu alloy in vitro. It was revealed that an addition of 5% Cu into pure Ti would not cause any negative effect on osteoblasts adhesion, proliferation and apoptosis cultured with Ti-Cu alloy. In addition, Ti-Cu alloy could significantly promote the osteogenic differentiation of MG 63 cells by upregulating the osteogenesis-related gene expressions including alkaline phosphatase (ALP), Collagen I (Colla I), osteopontin (OPN) and osteocalcin (OCN). These promising results suggest that the Ti-Cu alloy has great potential to be used as a multi-functional titanium implant for clinical applications.

Thyroid autoantibodies in pregnancy are associated with hypertensive disorders of pregnancy: Ma'anshan Birth Cohort Study.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) have been associated with adverse health outcomes for both mothers and children. Previous studies examining associations of maternal thyroid autoantibodies with HDP indicate conflicting results. The objective of this study was to examine associations of maternal thyroid autoantibody positivity in the first and the second trimesters with the risk of HDP. DESIGN, PARTICIPANTS AND MEASUREMENTS: In the Ma'anshan Birth Cohort study, a population-based prospective study in China, a total of 3474 pregnant women were enrolled between May 2013 and September 2014. Thyroid autoantibodies, including antithyroperoxidase autoantibody (TPOAb) and antithyroglobulin autoantibody (TgAb), as well as thyroid function tests, were measured in both the first and the second trimesters in 2893 pregnant women. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for the associations between thyroid autoantibodies and HDP. RESULTS: Multivariate logistic regression analyses showed that TPOAb positivity in the first trimester was associated with a 1.80 (95% CI = 1.17-2.78) increased odds of HDP after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.93, 95% CI = 1.17-3.18). In addition, TgAb positivity in the first trimester was associated with a higher risk of HDP (OR = 1.78, 95% CI = 1.16-2.73) after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.89, 95% CI = 1.15-3.11). These associations were also seen among euthyroid women. Women with positive TPOAb in the second trimester seemed to have a higher risk of gestational hypertension (OR = 1.87, 95% CI = 1.02-3.43) after adjustment for confounders. However, among euthyroid women, TPOAb positivity in the second trimester was not associated with HDP. The TgAb status in the second trimester was not associated with HDP. CONCLUSIONS: Our results show that TPOAb positivity and TgAb positivity in the first trimester are associated with an increased risk of HDP. These data demonstrate that these associations are even seen among euthyroid women.

Effects of rhBMP-2/7 Heterodimer and RADA16 Hydrogel Scaffold on Bone Formation During Rabbit Mandibular Distraction.

PURPOSE: The effects of a recombinant human bone morphogenetic protein-2/7 (rhBMP-2/7) heterodimer and a RADA16 (Ac-RADARADARADARADA-CONH2) hydrogel scaffold on bone formation during distraction osteogenesis were evaluated. MATERIALS AND METHODS: Forty New Zealand white rabbits, which underwent mandibular lengthening, were randomly divided into 5 groups. One group served as the control group. The others received 2 µg of rhBMP-2 homodimer, 2 µg of rhBMP-2/7 heterodimer, 100 µL of RADA16, or 100 µL of RADA16 plus 2 µg of rhBMP-2/7 heterodimer in the mandibular distraction gap at the beginning of distraction. Fluorine-18-labeled fluoride positron emission tomography was used to assess osteogenesis both after distraction and at the end of consolidation. Dual-energy x-ray absorptiometry (DEXA) examination and bone histologic findings were also evaluated. RESULTS: At the end of distraction, the radioactivity concentration in the distracted area was significantly greater in the RADA16 plus rhBMP-2/7 heterodimer group than in the other groups (P < .01). The differences among the other 4 groups were also statistically significant in the following order: rhBMP-2/7 heterodimer group greater than the rhBMP-2 homodimer group, which was greater than the RADA16 group (or control group; P < .05). However, the radioactivity concentration of the RADA16 group was slightly greater than that of the control group with a nonsignificant difference (P > .05). By the end of consolidation, the activity in the control group, RADA16 group, rhBMP-2 homodimer group, and rhBMP-2/7 heterodimer group had significantly diminished (P < .05). However, the activity in the RADA16 plus rhBMP-2/7 heterodimer group remained at the same level (P > .05). The DEXA results and bone histologic findings indicated that more callus regeneration was noted in the RADA16 plus rhBMP-2/7 heterodimer group than in any other group. CONCLUSIONS: The use of rhBMP-2/7 heterodimer and RADA16 hydrogel scaffold significantly promoted mandibular distraction osteogenesis.