Development and validation of a diagnostic prediction model for severe periventricular-intraventricular hemorrhage in newborns: insights from a retrospective analysis utilizing the MIMIC-III database

Abstract Objective: Periventricular-intraventricular hemorrhage is the most common type of intracranial bleeding in newborns, especially in the first 3 days after birth. Severe periventricular-intraventricular hemorrhage is considered a progression from mild periventricular-intraventricular hemorrhage and is often closely associated with severe neurological sequelae. However, no specific indicators are available to predict the progression from mild to severe periventricular-intraventricular in early admission. This study aims to establish an early diagnostic prediction model for severe PIVH. Method: This study was a retrospective cohort study with data collected from the MIMIC-III (v1.4) database. Laboratory and clinical data collected within the first 24 h of NICU admission have been used as variables for both univariate and multivariate logistic regression analyses to construct a nomogram-based early prediction model for severe periventricular-intraventricular hemorrhage and subsequently validated. Results: A predictive model was established and represented by a nomogram, it comprised three variables: output, lowest platelet count and use of vasoactive drugs within 24 h of NICU admission. The model's predictive performance showed by the calculated area under the curve was 0.792, indicating good discriminatory power. The calibration plot demonstrated good calibration between observed and predicted outcomes, and the Hosmer-Lemeshow test showed high consistency (p = 0.990). Internal validation showed the calculated area under a curve of 0.788. Conclusions: This severe PIVH predictive model, established by three easily obtainable indicators within the NICU, demonstrated good predictive ability. It offered a more user-friendly and convenient option for neonatologists.

Identification of HIST1H2BH as the hub gene associated with multiple myeloma using integrated bioinformatics analysis.

OBJECTIVES: Identifying the specific biomarkers and molecular signatures of MM might provide novel evidence for MM prognosis and targeted therapy. METHODS: Bioinformatic analyses were performed through GEO and TCGA datasets. The differential expression of HIST1H2BH in MM sample was validated by the qRT-PCR. And the CCK-8 assay was performed to detect the proliferation activity of HIST1H2BH on MM cell lines. RESULTS: A total of 793 DEGs were identified between bone marrow plasma cells from newly diagnosed myeloma and normal donors in GSE6477. Among them, four vital genes (HIST1H2AC, HIST1H2BH, CCND1 and TCF7L2) modeling were constructed. The increased HIST1H2BH expression was correlated with worse survival of MM based on TCGA datasets. The transcriptional expression of HIST1H2BH was significantly up-regulated in primary MM patients. And knockdown HIST1H2BH decreased the proliferation of MM cell lines. CONCLUSIONS: We have identified up-regulated HIST1H2BH in MM patients associated with poor prognosis using integrated bioinformatical methods.

YBX1 Underwent Phase Separation into Stress Granules Stimulated by Ionizing Radiation.

Stress granules (SGs) are formed through liquid-liquid phase separation (LLPS), in response to external stimuli. YBX1, an integral component of SGs, plays a crucial role in tumor progression and cellular stress response. This study aims to elucidate the mechanisms and specific biological implications of YBX1 in SG formation, along with the identification of key regions and interacting proteins. Our observations indicate that YBX1 rapidly undergoes liquid-liquid phase separation, leading to SG formation in response to 8 Gy X-ray irradiation within 1 h, with SGs reverting to their original state after 5 h. There was a potential interaction between ATXN2L and YBX1, persisting YBX1 within the SGs. Our data suggested a potential interaction between ATXN2L and YBX1, and it remained associated with YBX1 within the SGs. Furthermore, our subsequent studies demonstrate that targeting ATXN2L can diminish the recruitment of YBX1 to stress granules (SGs), consequently enhancing the radiosensitivity of HeLa cells.

OTUD4 regulates metastasis and chemoresistance in melanoma by stabilizing Snail1.

Melanoma is the most aggressive form of skin cancer with rapidly increased incidence worldwide especially in the Caucasian population. Surgical excision represents the curative treatment choice in patients with early-stage disease. However, the therapeutic outcomes in patients with metastatic melanoma remains unsatisfactory. Thus, understanding molecular mechanisms contributing to metastasis and chemoresistance is critical for new improved therapies of melanoma. Snail1, an important epithelial-mesenchymal transition transcription factors (EMT-TFs), is critical to induce the EMT process, thereby contributing to cancer metastasis. However, the involvement of Snail1 in melanoma metastasis remains elusive and the underlying mechanism to regulate Snail1 in melanoma needs to be further investigated. Here, we identified OTUD4 as a novel deubiquitinase of Snail1 in melanoma. Moreover, the depletion of OTUD4 in melanoma cells markedly inhibited Snail1 stability and Snail1-driven malignant phenotypes both in vitro and in vivo. Overall, our study establishes OTUD4 as a novel therapeutic target in metastasis and chemoresistance of melanoma by stabilizing Snail1 and provides a rationale for potential therapeutic strategies of melanoma.

Correlations between contrast-enhanced ultrasound and microvessel density in non-small cell lung cancer: A prospective study.

Background: Immunohistochemical microvessel density (MVD) is an early indicator of angiogenesis and it could be used to evaluate the therapeutic efficacy of non-small cell lung cancer (NSCLC). We sought to identify the ability of contrast-enhanced ultrasound (CEUS) in evaluating MVD of subpleural NSCLC. Methods: We prospectively collected CEUS data of NSCLC confirmed by ultrasound-guided transthoracic needle biopsy from October 2019 to February 2021, The MVD of NSCLC counted by CD34-positive vessels of immunohistochemical staining. Microflow enhancement (MFE) of CEUS was divided into "dead wood", "cotton", and "vascular" patterns. Pathology subgroup and MVD between different MFE patterns were analyzed, respectively. The arrival time, time to peak, peak intensity (PI), and area under curve (AUC) derivefrom time-intensity curve of CEUS with MVD in NSCLC and its pathological subgroups (adenocarcinoma and squamous cell carcinoma) were subjected to correlation analysis. Results: A total of 87 patients were included in this study, consisting of 53 cases of adenocarcinoma and 34 cases of squamous cell carcinoma with a mean MVD of 27.8 ± 12.2 mm-1. There was a significant statistical difference in MFE patterns between two pathological subgroups (p < 0.05). Besides, the MVD of "cotton" and "vascular" patterns were significantly higher than that of "dead wood" pattern (both of p < 0.05), whereas there was no significant difference in MVD between "cotton" pattern and "vascular" pattern. PI and AUC of CEUS were positively correlated with the MVD of NSCLC (r = 0.497, p < 0.001, and r = 0.367, p < 0.001, respectively). Besides, PI and AUC of CEUS were positively correlated with the MVD of squamous cell carcinoma (r = 0.802, and r = 0.663, respectively; both of p < 0.001). Only the PI was positively correlated with the MVD of lung adenocarcinoma (r = 0.288, p = 0.037). Conclusions: MFE patterns and quantitative parameters of CEUS had good correlation with MVD of NSCLC, especially in squamous cell carcinoma.

The Tumorigenic Effect of lncRNA AFAP1-AS1 is Mediated by Translated Peptide ATMLP Under the Control of m6 A Methylation.

Long noncoding RNAs (lncRNAs) in eukaryotic transcripts have long been believed to regulate various aspects of cellular processes, including carcinogenesis. Herein, it is found that lncRNA AFAP1-AS1 encodes a conserved 90-amino acid peptide located on mitochondria, named lncRNA AFAP1-AS1 translated mitochondrial-localized peptide (ATMLP), and it is not the lncRNA but the peptide that promotes the malignancy of nonsmall cell lung cancer (NSCLC). As the tumor progresses, the serum level of ATMLP increases. NSCLC patients with high levels of ATMLP display poorer prognosis. Translation of ATMLP is controlled by m6 A methylation at the 1313 adenine locus of AFAP1-AS1. Mechanistically, ATMLP binds to the 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) and inhibits its transport from the inner to the outer mitochondrial membrane, which antagonizes the NIPSNAP1-mediated regulation of cell autolysosome formation. The findings uncover a complex regulatory mechanism of NSCLC malignancy orchestrated by a peptide encoded by a lncRNA. A comprehensive judgment of the application prospects of ATMLP as an early diagnostic biomarker for NSCLC is also made.

Phosphorylation of USP29 by CDK1 Governs TWIST1 Stability and Oncogenic Functions.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy with limited therapy options. TWIST1, a key transcriptional factor of epithelial-mesenchymal transition (EMT), contributes to self-renewal of cancer stem-like cells (CSCs), chemo-resistance, metastasis, and TNBC-related death. However, the mechanism by which TWIST1 is deregulated in TNBC remains elusive. Here, USP29 is identified as a bona fide deubiquitinase of TWIST1. The deubiquitination of TWIST1 catalyzed by USP29 is required for its stabilization and subsequent EMT and CSC functions in TNBC, thereby conferring chemotherapeutic resistance and metastasis. Furthermore, the results unexpectedly reveal that CDK1 functions as the direct USP29 activator. Mechanistically, CDK1-mediated phosphorylation of USP29 is essential for its deubiquitinase activity toward TWIST1 and TWIST1 driven-malignant phenotypes in TNBC, which could be markedly mitigated by the genetic ablation or pharmacological inhibition of CDK1. Moreover, the histological analyses show that CDK1 and USP29 are highly upregulated in TNBC samples, which positively correlate with the expression of TWIST1. Taken together, the findings reveal a previously unrecognized tumor-promoting function and clinical significance of the CDK1-USP29 axis through stabilizing TWIST1 and provide the preclinical evidence that targeting this axis is an appealing therapeutic strategy to conquer chemo-resistance and metastasis in TNBC.

vsiRNA18 derived from tobacco curly shoot virus can regulate virus infection in Nicotiana benthamiana.

Virus-derived small interfering RNAs (vsiRNAs) play important roles in regulating host endogenous gene expression to promote virus infection and induce RNA silencing to suppress virus infection. However, to date, how vsiRNAs affect geminivirus infection in host plants has been less studied. In this study, we found that tobacco curly shoot virus (TbCSV)-derived vsiRNA18 (TvsiRNA18) can regulate TbCSV infection in Nicotiana benthamiana plants. The virus-mediated small RNA expression system and stable transformation technique were used to clarify the molecular role of TvsiRNA18 in TbCSV infection. The results indicate that TvsiRNA18 can aggravate disease symptoms in these plants and enhance viral DNA accumulation. ATP-dependent RNA helicase (ATP-dRH) was proven to be a target of TvsiRNA18, and down-regulation of ATP-dRH in plants was shown to induce virus-like leaf curling symptoms and increase TbCSV infection. These results suggest that TvsiRNA18 is an important regulator of TbCSV infection by suppressing ATP-dRH expression. This is the first report to demonstrate that TbCSV-derived vsiRNA can target host endogenous genes to affect symptom development, which helps to reveal the molecular mechanism of symptom occurrence after the virus infects the host.

Unveiling the links between physical activity, self-identity, social anxiety, and emotional eating among overweight and obese young adults.

Introduction: Emotional eating not only contributes to physical obesity but also leads to the experience of guilt and shame, exacerbating emotional problems. Increasing physical activity, adopting a balanced diet, and seeking psychological support help improve emotional eating issues in overweight or obese young adults, enhancing overall mental and physical well-being. Methods: This study investigates the correlation between physical activity, self-identity, social anxiety, and emotional eating among 373 overweight and obese college students aged 18-26 in central China. By utilizing AMOS v.26, a structural equation model was constructed to examine the hypotheses. Results: The findings reveal that physical activity significantly influences self-identity and social anxiety, which, in turn, significantly impact emotional eating. Moreover, self-identity and social anxiety serve as mediators in the relationship between physical activity and emotional eating. These results emphasize the role of physical activity in mitigating emotional eating among young individuals struggling with overweight and obesity. Discussion: Consequently, the government and relevant agencies are urged to address the issue of obesity among young adults and provide support for their engagement in physical activity.

Diagnostic ability and its influenced factors of ultrasound-guided percutaneous pleural needle biopsy diagnosis for malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is a highly invasive malignant tumor. Ultrasound guidance has the advantages of real-time, convenience and nonradiative. We sought to identify diagnostic value and its influenced factors of ultrasound-guided percutaneous pleural needle biopsy (US-PPNB) for MPM. Methods: Patients who underwent US-PPNB between March 2014 and March 2020 and were finally diagnosed with MPM were retrospectively analyzed. We retrospectively analyzed the US-PPNBs pathological results of all patients clinically confirmed as MPM, and divided US-PPNBs into correctly and incorrectly diagnosed groups. Patient, thoracic, and biopsy variables that affected diagnostic accuracy were assessed. All variables significant on univariate analyses were subjected to multivariate logistic regression to identify significant predictors of diagnostic accuracy. We derived cutoffs for all significant continuous variables and used the Mantel-Haenszel test to determine whether the diagnostic accuracy of US-PPNB for MPM increased with pleural thickness. Results: In total, 49 patients with clinically confirmed MPM underwent US-PPNB; 37 diagnoses were correct and 12 were incorrect (accuracy = 75.5%). The pleura was significantly thicker in the correctly diagnosed group (p < 0.001). The pleural thickness cutoff was 4.15 mm and diagnostic accuracy increased with pleural thickness grade (p for trend <0.05). The diagnostic accuracy was significantly higher when 16-G rather than 18-G biopsy needles were used (p < 0.05). Multivariate logistic regression showed that pleural thickness (odds ratio: 17.2, 95% confidence interval: 2.8-104.1, p = 0.002) and needle size (odds ratio: 6.8, 95% confidence interval: 1.0-44.5, p = 0.044) independently predicted diagnostic accuracy. Conclusion: US-PPNB afforded high MPM diagnostic accuracy, and pleural thickness and needle size significantly impacted accuracy.

A Comparison of the Performances of Artificial Intelligence System and Radiologists in the Ultrasound Diagnosis of Thyroid Nodules.

AIMS: The purpose of this paper is to prospectively evaluate the performance of an artificial intelligence (AI) system in diagnosing thyroid nodules and to assess its potential value in comparison with the performance of radiologists with different levels of experience, as well as the factors affecting its diagnostic accuracy. BACKGROUND: In recent years, medical imaging diagnosis using AI has become a popular topic in clinical application research. OBJECTIVE: This study aimed to evaluate the performance of an AI system in diagnosing thyroid nodules and compare it with the performance levels of different radiologists. METHODS: This study involved 426 patients screened for thyroid nodules at the First Affiliated Hospital of Guangzhou Medical University between July 2017 and March 2019. All of the nodules were evaluated by radiologists with various levels of experience and an AI system. The diagnostic performances of two junior and two senior radiologists, an AI system, and an AI-assisted junior radiologist were compared, as were their diagnostic results with respect to nodules of different sizes. RESULTS: The senior radiologists, the AI system, and the AI-assisted junior radiologist performed better than the junior radiologist (p < 0.05). The area under the curves of the AI system and the AI-assisted junior radiologist were similar to the curve of the senior radiologists (p > 0.05). The diagnostic results concerning the two nodule sizes showed that the diagnostic error rates of the AI system, junior radiologists, and senior radiologists for nodules with a maximum diameter of ≤1 cm (Dmax ≤ 1 cm) were higher than those for nodules with a maximum diameter of 1 cm (Dmax > 1 cm) (23.4% vs. 12.1%, p = 0.002; 26.6% vs. 7.3%, p < 0.001; and 38.3% vs. 14.6%, p < 0.001). CONCLUSION: The AI system is a decision-making tool that could potentially improve the diagnostic efficiency of junior radiologists. Micronodules with Dmax ≤ 1cm were significantly correlated with diagnostic accuracy; accordingly, more micronodules of this size, in particular, should be added to the AI system as training samples. Other: The system could be a potential decision-making tool for effectively improving the diagnostic efficiency of junior radiologists in the community.

Downregulation of Long Noncoding RNA CRYBG3 Enhances Radiosensitivity in Non-Small Cell Lung Cancer Depending on p53 Status.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with high recurrence and metastasis rates, and more than half of the patients diagnosed with NSCLC receive local radiotherapy. However, the intrinsic radio-resistance of cancer cells is a major barrier to effective radiotherapy for NSCLC. CRYBG3 is a long noncoding RNA (lncRNA) that was originally identified to be upregulated in NSCLC and enhanced metastasis of NSCLC cells by interacting with eEF1A1 to promote murine double minute 2 (MDM2) expression. The aims of this study were to reveal the contribution of CRYBG3 to the radioresistance of NSCLC and determine whether that is associated with MDM2-p53 pathway. Therefore, CRYBG3 was stably downregulated in A549 (wild-type p53) and H1299 (deficient p53) cells by infecting short hairpin RNA (shRNA) lentiviral particles. The results showed that downregulation of CRYBG3 increased DNA damage, enhanced apoptosis and pro-apoptotic protein expression in A549 or p53-overexpressed H1299 cells but not in H1299 or p53-silenced A549 cells after X-ray irradiation. However, the contribution of CRYBG3 to radioresistance was abolished by eEF1A1 or MDM2 knockdown in A549 cells. Thus, we concluded that downregulation of CRYBG3 enhanced radiosensitivity by reducing MDM2 expression then leading to decreased MDM2-mediated degradation of p53 in wild-type p53 expressing NSCLC cells. These findings suggested that CRYBG3 can be a potential target for therapeutic intervention of certain lung cancer subtypes.

Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis.

The occurrence of distant tumor metastases is a major barrier in non-small cell lung cancer (NSCLC) therapy, and seriously affects clinical treatment and patient prognosis. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to be crucial regulators of metastasis in lung cancer. The aim of this study was to reveal the underlying mechanisms of a novel lncRNA LNC CRYBG3 in regulating NSCLC metastasis. Experimental results showed that LNC CRYBG3 was upregulated in NSCLC cells compared with normal tissue cells, and its level was involved in these cells' metastatic ability. Exogenously overexpressed LNC CRYBG3 increased the metastatic ability and the protein expression level of the metastasis-associated proteins Snail and Vimentin in low metastatic lung cancer HCC827 cell line. In addition, LNC CRYBG3 contributed to HCC827 cell metastasis in vivo. Mechanistically, LNC CRYBG3 could directly combine with eEF1A1 and promote it to move into the nucleus to enhance the transcription of MDM2. Overexpressed MDM2 combined with MDM2 binding protein (MTBP) to reduce the binding of MTBP with ACTN4 and consequently increased cell migration mediated by ACTN4. In conclusion, the LNC CRYBG3/eEF1A1/MDM2/MTBP axis is a novel signaling pathway regulating tumor metastasis and may be a potential therapeutic target for NSCLC treatment.

Hemoptysis complicating ultrasound-guided transthoracic needle lung biopsy: air bronchial sign is a risk predictor.

BACKGROUND: Hemoptysis is the most frequently reported complication of ultrasound-guided transthoracic needle lung biopsy (US-TTLB). However, factors influencing the occurrence of hemoptysis as a result of US-TTLB remain uncertain. Therefore, the aim of this study was to evaluate the incidence of hemoptysis as a complication of US-TTLB and to identify the related risk factors. METHODS: We retrospectively analyzed all data of patients who underwent US-TTLB from February 2013 through December 2016. The incidence, severity, and treatment of hemoptysis in each case were carefully recorded. Study variables were classified into patient-related factors (age, sex, smoking history, pulse oxygen saturation, laboratory tests and emphysema), biopsy-related factors (use of contrast agent, number of punctures and operators), and lesion-related factors (lesion location, size, pathology, length of puncture path and the grade of air bronchial sign). Univariate and multivariate logistic regression analyses were performed to analyze the risk factors of hemoptysis. We investigated whether incidence of hemoptysis increased according to increased grade of air bronchial sign by Mantel-Haenszel test. RESULTS: A total of 209 patients were evaluated. Hemoptysis occurred in 20 of the 209 patients (9.6%). In univariate analysis, the lesion pathology (P=0.037) and grade of air bronchial sign (P<0.001) were statistically significant factors between the hemoptysis group and the non-hemoptysis group. In multivariate analysis, the presence of multi-air bronchogram in sonographic image (odds ratio =8.946; 95% confidence interval: 2.873-27.863; P<0.001) was a statistically significant predictive risk factor for hemoptysis complicating US-TTLB. There was a significant tendency for incidence of hemoptysis with the grade of air bronchial sign (P<0.001). CONCLUSIONS: We found that the rate of hemoptysis complicating US-TTLB was 9.6% and the severity of hemoptysis was not serious. Target lesion without air bronchogram is a safety sign, minor bronchogram means relatively low-risk, while multiple bronchogram is a highly dangerous ultrasound sign of hemoptysis.

Human adipose-derived mesenchymal progenitor cells plus microfracture and hyaluronic acid for cartilage repair: a Phase IIa trial.

Aim: This study aimed to preliminarily evaluate the safety and efficacy of human adipose-derived mesenchymal progenitor cells (haMPCs) in combination with microfracture and hyaluronic acid (HA) for treating cartilage defects. Materials & methods: A total of 30 patients with medial femoro-tibial condylar cartilage defects were randomized into three groups: arthroscopic microfracture group and normal saline injection, arthroscopic microfracture and intra-articular injection of HA, or arthroscopic microfracture in combination with intra-articular injection of HA and haMPCs. Results & conclusions: The data demonstrated that intra-articular injection of haMPCs plus microfracture and HA is a safe procedure to improve joint function in patients with knee cartilage defects. These findings provide an impetus for future research on this treatment. ClinicalTrials.gov Identifier: NCT02855073.

Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats.

BACKGROUND: Osteoarthritis (OA) is a common degenerative disease of synovial joints caused by inflammation. Acteoside (ACT), a major component and lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha, has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of ACT on inflammatory responses and joint protection in OA rats. METHODS: Cell proliferation was examined by MTT and colony formation assay. Apoptosis was analyzed using flow cytometry with Annexin V/PI staining. ELISA was employed to examine the concentration of inflammatory cytokines. OA rat model was established by surgery stimulation. RESULTS: ACT treatment significantly inhibited the upregulation of inflammatory cytokines induced by IL-1ß in primary chondrocytes, including IL-6, IL-12, TNF-α and IFN-γ. ACT stimulation also enhanced the cell proliferation, while inhibited cell apoptosis in IL-1ß-treated chondrocytes. Consistently, ACT treatment led to downregulation of cleaved-caspase-3 and apoptosis regulator Bax, and upregulation of Bcl-2. Furthermore, ACT treatment inhibited IL-1ß-induced activation of JAK/STAT pathway. The results were confirmed in surgery-induced OA rat model. Moreover, ACT treatment significantly inhibited synovial inflammation and articular chondrocyte apoptosis in OA rats. CONCLUSION: Our findings indicate that ACT has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating JAK/STAT signaling pathway.

Ultrasound-guided pleural cutting needle biopsy: accuracy and factors influencing diagnostic yield.

BACKGROUND: The aim of this study was to retrospectively investigate the diagnostic accuracy of ultrasound-guided pleural cutting needle biopsy (US-guided PCNB) and the potential factors influencing diagnostic yield. METHODS: From July 2014 to June 2016, a total of 147 percutaneous US-guided PCNBs in 144 patients were retrospectively reviewed. The final diagnosis was confirmed by histopathological analysis and follow-up. We calculated diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) and divided all cases into group of correct diagnoses (true-positive and true-negative cases) and group of incorrect diagnoses (false-positive, false-negative, and inconclusive cases). Univariate and multivariate logistic regression analyses were performed to analyze the differences of influencing factors (patient, pleura, and biopsy-associated factors) in the between the two groups. RESULTS: Seven patients were excluded because of loss to follow-up. A total of 140 cases were ultimately included (105 males and 35 females). There were 105 cases in the correct diagnosis group, and 35 cases in the incorrect diagnosis group. The overall accuracy of US-PCNB was 75.0% and the sensitivity, specificity, PPV, NPV in malignant diagnosis were 58.1%, 99.0%, 96.2%, and 84.2%, respectively. On univariate analysis, variables affecting diagnostic accuracy of US-PCNB were the pleural thickness (<3 mm in thickness 61.0%, ≥3 mm in thickness 85.2%; P=0.001), morphology (non-nodular pleura 71.4%, nodular pleura 95.2%; P=0.026), and needle size (18 G 69.1%, 16 G 87.0%; P=0.022). Finally multivariate logistic regression demonstrated that pleural thickness [odds ratio (OR): 0.278, P=0.003] and needle size (OR: 0.291, P=0.018) independently predicted diagnostic accuracy. CONCLUSIONS: Pleural thickness and the size of the biopsy needle were significantly correlated with the diagnostic yield.

Lithium posttreatment confers neuroprotection through glycogen synthase kinase-3ß inhibition in intracerebral hemorrhage rats.

OBJECTIVE Inflammation and apoptosis are two key factors contributing to secondary brain injury after intracerebral hemorrhage (ICH). The objective of this study was to evaluate the effects of lithium posttreatment on behavior, brain atrophy, inflammation, and perihematomal cell death. Furthermore, the authors aimed to determine the role of the pro-apoptotic glycogen synthase kinase-3ß (GSK-3ß) after experimental ICH. METHODS Male Sprague-Dawley rats (n = 108) were subjected to intracerebral infusion of semicoagulated autologous blood. Window of opportunity and dose optimization studies of lithium on ICH-induced injury were performed by measuring neurological deficits. Animals with ICH received vehicle administration or lithium posttreatment (60 mg/kg) for up to 21 days. Hemispheric atrophy was evaluated. Perihematomal cell death was quantified through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The number of myeloperoxidase (MPO)-positive neutrophils and OX42-positive microglia in the perihematomal areas were calculated. Western blotting was used for the quantification of GSK-3ß, heat shock protein 70 (HSP70), nuclear factor-κB p65 (NF-κB p65), and cy-clooxygenase-2 (COX-2). RESULTS Lithium, at a dose of 60 mg/kg initiated from 2 hours after injury, exhibited the best effects of improving neurological outcomes 3, 5, 7, 14, 21, and 28 days after ICH, reduced the hemispheric atrophy at 42 days after surgery, and reduced the number of TUNEL-positive cells, MPO-positive neutrophils, and OX42-positive microglia in the perihematomal areas. Furthermore, lithium posttreatment modulated GSK-3ß, increased HSP70, and decreased NF-κB p65 and COX-2 expression in the ipsilateral hemisphere. CONCLUSIONS Lithium posttreatment at a dose of 60 mg/kg, initiated beginning 2 hours after injury, improves functional and morphological outcomes, and inhibits inflammation and perihematomal cell death in a rat model of semicoagulated autologous blood ICH through inactivation of GSK-3ß.

Experimental intracerebral haemorrhage: description of a semi-coagulated autologous blood model in rats.

OBJECTIVES: A major limitation of intracerebral haemorrhage (ICH) research is the lack of reproducible animal models. The purpose of the present study was to produce experimental haemorrhages and to characterise the lesion by histology and behaviour in rats. METHODS: A total of 180 male SD rats were anaesthetised with chloral hydrate. Rats were placed in a stereotactic frame, and a microinjector was introduced through a burr hole into the right striatum. Each rat received an injection of 60 µL of semi-coagulated autologous whole blood over 6  minutes. The needle was slowly withdrawn 40 minutes after the injection. Control rat had only needle insertion. Time courses of haematoma resolution and pathological changes after intrastriatal injection of semi-coagulated autologous blood were observed. Neurological status was evaluated on days 1, 3, 5, 7, 14 and 21.The behavioural tests used were forelimb placing and a corner turn test. RESULTS: Rats with ICH had a marked, persistent neurological deficit and a highly reproduced haematoma in shape and size. Histologically, haematoma was observed at 1, 3, 5 and 7 days and cysts at 3 weeks. Behavioural abnormalities were present for 14  days, with the recovery of function occurring during the third week. CONCLUSIONS: The present ICH model in rats produces a consistent neurological deficit and reproducible haematoma in shape and size. This model could be useful to evaluate the future pharmaceutical therapies in ICH.