Bedside ultrasound-assisted puncture and drainage under local anesthesia: A novel approach for early post-operative space-occupying tumor bed cysts of glioma resection.

OBJECTIVES: To investigate the causes of space-occupying tumor bed cysts formed early after glioma resection by measuring the osmotic pressure gradient between cystic fluid, serum, and cerebrospinal fluid (CSF) and propose a new method of bedside ultrasound-assisted puncture and drainage (UAP&D) under local anesthesia for treatment. METHODS: Bedside UAP&D under local anesthesia was performed through a burr hole on the skull flap.Following a successful puncture, cystic fluid was collected, while blood and CSF were obtained through vein and lumbar puncture, respectively. The osmotic pressure of all fluids collected was measured. The appearance, biochemical composition, and results of microbial culture of cystic fluid and CSF were analyzed. Within 24 h after UAP&D, a CT examination and Glasgow coma scale (GCS) were assessed. RESULTS: The osmotic pressure of cystic fluid was higher than that of serum and CSF. White blood cell count and protein concentration were higher in the cystic fluid compared to the CSF. Conversely, the concentration of chloride ions and glucose were lower. CT scan confirmed the correct placement of the cysts' drainage tube and that the cysts' volume decreased significantly with continued drainage. Accompanied by a reduction in the volume of cysts, there were significant improvements in GCS score within 24 h after UAP&D. All drainage tubes were removed within 2-5 days, and no puncture tract hemorrhage or infection was observed. CONCLUSION: The osmotic pressure gradient between cystic fluid, serum, and CSF caused the formation of early post-operative space-occupying tumor bed cysts for glioma. UAP&D aligns with the concept that micro-invasive neurosurgery is an effective treatment method for such cysts.

Single-cell analysis of a progressive Rosai-Dorfman disease affecting the cerebral parenchyma: a case report.

Neurologic Rosai-Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease.

Pioglitazone, a peroxisome proliferator­activated receptor γ agonist, induces cell death and inhibits the proliferation of hypoxic HepG2 cells by promoting excessive production of reactive oxygen species.

Hypoxia is a hallmark of solid tumors. Hypoxic cancer cells adjust their metabolic characteristics to regulate the production of cellular reactive oxygen species (ROS) and facilitate ROS-mediated metastasis. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that regulates the transcription of fatty acid metabolism-related genes that have a key role in the survival and proliferation function of hypoxic cancer cells. In the present study, mRNA expression in HepG2 cells under chemically induced hypoxia was assessed. The protein expression levels of hypoxia-inducible factor 1α (HIF-1α) were measured using western blotting. Following treatment with the PPARγ agonist pioglitazone, cell viability was assessed using a Cell Counting Kit-8 assay, whilst cell proliferation and death were determined using 5-ethynyl-2'-deoxyuridine incorporation staining, and calcein-acetoxymethyl ester and propidium iodide staining, respectively. Cellular ROS production was assessed using dihydroethidium staining. Cobalt chloride was used to induce hypoxia in HepG2 cells, which was evaluated using HIF-1α expression. The results revealed that the mRNA expression of PPARγ, CD36, acetyl-co-enzyme A dehydrogenase (ACAD) medium chain (ACADM) and ACAD short-chain (ACADS) was downregulated in hypoxic HepG2 cells. The PPARγ agonist pioglitazone decreased the cell viability of hypoxic HepG2 cells by inhibiting cell proliferation and inducing cell death. Following treatment with the PPARγ agonist pioglitazone, hypoxic HepG2 cells produced excessive ROS. ROS-mediated cell death induced by the PPARγ agonist pioglitazone was rescued with the antioxidant N-acetyl-L-cysteine. The downregulated mRNA expression of PPARγ, CD36, ACADM and ACADS was not reverted by a PPARγ agonist in hypoxic HepG2 cells. By contrast, the PPARγ agonist suppressed the mRNA expression of BCL2, which was upregulated in hypoxic HepG2 cells. In summary, the PPARγ agonist stimulated excessive ROS production to inhibit cell proliferation and increase the death of hypoxic HepG2 cells by decreasing BCL2 mRNA expression, suggesting a negative association between PPARγ and BCL2 in the regulation of ROS production in hypoxic HepG2 cells.

Case report: Two case reports of cryptogenic brain abscess caused by Fusobacterium nucleatum and literature review.

Brain abscess originates from a localized cerebritis area of brain parenchyma, remaining a refractory infectious disease in the central nervous system. Causative pathogens can be wide-ranging, including bacteria, fungi, or parasites; thus, precise pathogen identification and individualized antimicrobial therapy determine patients' outcomes. Here, we report two cases where both patients only presented with limb dysfunction, but without symptoms, signs, or biological evidence of infection. Samples were obtained through brain stereoscopic surgeries and microbial identifications were performed to confirm the infection of Fusobacterium nucleatum. Further appropriate treatments were given, and the patients recovered well. Patient 1 was a 73-year-old male with a 20-day history of left-sided limbs weakness. A brain MRI showed a space-occupying lesion with a heterogeneously ring-enhancement character in the right frontal lobe. This patient underwent puncture biopsy of the lesion with robot-assisted guidance to confirm a brain abscess. Empirical antibiotic therapy was immediately given until the pathogen was identified as Fusobacterium nucleatum; thus, he received specific antibiotic therapy with metronidazole and recovered well after treatment. Patient 2 was a 22-year-old female with heart disease history who complained of right-sided limb weakness for nine days. A brain MRI showed a circular enhanced lesion with a thin capsule wall and surrounding edema in the left frontal lobe. This patient underwent puncture drainage of the lesion with robot-assisted guidance and a brain abscess was confirmed. Empirical antibiotic therapy was given until the pathogen was identified as Fusobacterium nucleatum and then she also received metronidazole treatment. Her symptoms recovered and the lesion disappeared after 1 month. Hence, we reviewed the diagnosis and treatment of cryptogenic brain abscess caused by Fusobacterium nucleatum and highlight that precise neurosurgical interventions and identification of causative pathogens are crucial for the management of brain abscess.

Effects of Serotonin on Cell Viability, Permeability of Bovine Mammary Gland Epithelial Cells and Their Transcriptome Analysis.

Serotonin (5-HT) has been reported to play an important role in mammary gland involution that is defined as the process through which the gland returns to a nonlactating state. However, the overall picture of the regulatory mechanisms of 5-HT and the effects of serotonylation on mammary gland involution still need to be further investigated. The current study aimed to investigate the effects of 5-HT on global gene expression profiles of bovine mammary epithelial cells (MAC-T) and to preliminarily examine whether the serotonylation involved in the mammary gland involution by using Monodansylcadaverine (MDC), a competitive inhibitor of transglutaminase 2. Results showed that a high concentration of 5-HT decreased viability and transepithelial electrical resistance (TEER) in MAC-T cells. Transcriptome analysis indicated that 2477 genes were differentially expressed in MAC-T cells treated with 200 µg/mL of 5-HT compared with the control group, and the Notch, p53, and PI3K-Akt signaling pathways were enriched. MDC influenced 5-HT-induced MAC-T cell death, fatty acid synthesis, and the formation and disruption of tight junctions. Overall, a high concentration of 5-HT is able to accelerate mammary gland involution, which may be regulated through the Notch, p53, and PI3K-Akt signaling pathways. Serotonylation is involved in bovine mammary gland involution.

HOXD-AS2-STAT3 feedback loop attenuates sensitivity to temozolomide in glioblastoma.

AIMS: Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non-coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD-AS2-affected temozolomide sensitivity in glioblastoma. METHODS: We analyzed and validated the aberrant HOXD-AS2 expression in glioma specimens. Then we explored the function of HOXD-AS2 in vivo and in vitro and a clinical case was also reviewed to examine our findings. We further performed mechanistic experiments to investigate the mechanism of HOXD-AS2 in regulating TMZ sensitivity. RESULTS: Elevated HOXD-AS2 expression promoted progression and negatively correlated with prognosis of glioma; HOXD-AS2 attenuated temozolomide sensitivity in vitro and in vivo; The clinical case also showed that lower HOXD-AS2 sensitized glioblastoma to temozolomide; STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to form a complex and sequentially upregulate STAT3 signaling, thus forming a positive feedback loop regulating TMZ sensitivity in glioblastoma. CONCLUSION: Our study elucidated the crucial role of the HOXD-AS2-STAT3 positive feedback loop in regulating TMZ sensitivity, suggesting that this could be provided as a potential therapeutic candidate of glioblastoma.

Case Report: An Intracranial Aspergillus Infection with Cyst Formation.

Intracranial fungal infection is a rare condition that often requires surgical intervention. In this study, we present a case of intracranial fungal infection with a space-occupying effect and a long medical history of five years. We comprehensively evaluated the medical history, symptoms, imaging manifestations, and pathological examinations of the patient to confirm this rare case of fungal infection with cyst formation. Moreover, we reviewed the literature on intracranial fungal infection, hoping to draw awareness and attention to this rare disease.

The impact of drug-eluting bead (vs. conventional) transarterial chemoembolization on hepatic fibrosis in treating intermediate or advanced hepatocellular carcinoma.

OBJECTIVE: Limited studies have reported the impact of drug-eluting bead transarterial chemoembolization (DEB-TACE) on hepatic fibrosis in hepatocellular carcinoma (HCC). This study evaluated multiple hepatic fibrosis indicators, aiming to comprehensively compare the influence of DEB-TACE and conventional transarterial chemoembolization (cTACE) on hepatic fibrosis in treating HCC patients. METHODS: Intermediate/advanced HCC patients (N = 121) were divided into the DEB-TACE group (n = 62) and the cTACE group (n = 59) based on their chosen treatment. Serum hyaluronic acid (HA), pro-collagen type-III (PC-III), collagen type-IV (IV-C), and laminin (LN) were detected; aminotransferase to platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated; liver stiffness measurement (LSM) was assessed by real-time shear wave elastography. RESULTS: HA, PC-III, IV-C, and LN at 1 month after the second TACE and at 12 months after the first TACE were all decreased in DEB-TACE group compared with cTACE group (all P < .050). Then, APRI, FIB-4, and LSM were further assessed, which also showed a decreasing trend at aforementioned timepoints in DEB-TACE group compared with cTACE group (all P < .050). Additionally, the multivariate logistic regression analysis revealed that DEB-TACE (vs. cTACE) was independently associated with reduced occurrence of severe hepatic fibrosis at 12 months (OR = 0.215, 95%CI: 0.058-0.802, P = .022). Concerning the liver function indexes, alanine aminotransferase, aspartate aminotransferase, and total bilirubin after treatment were not different between the two groups (all P > .050). CONCLUSION: DEB-TACE displays attenuated hepatic fibrosis progression and noninferior tolerance compared to cTACE in treating intermediate- or advanced-stage HCC patients.

Effects of Running in Minimal and Conventional Footwear on Medial Tibiofemoral Cartilage Failure Probability in Habitual and Non-Habitual Users.

This study examined the effects of minimal and conventional running footwear on medial tibiofemoral cartilage mechanics and longitudinal failure probability. The current investigation examined twenty males who habitually ran in minimal footwear and 20 males who habitually ran in conventional footwear. Kinematic data during overground running were collected using a motion-capture system and ground reaction forces using a force plate. Medial tibiofemoral loading was examined using musculoskeletal simulation and cartilage failure probability via probabilistic modelling. In habitual minimal footwear users, peak medial tibiofemoral cartilage force, stress and strain were significantly greater in conventional (force = 7.43 BW, stress = 5.12 MPa and strain = 0.30), compared to minimal footwear (force = 7.11 BW, stress 4.65 MPa and strain = 0.28), though no significant differences in these parameters were evident in non-habitual minimal footwear users (conventional: force = 7.50 BW, stress = 5.05 MPa and strain = 0.30; minimal: force = 7.40 BW, stress = 4.77 MPa and strain = 0.29). However, in both habitual and non-habitual minimal footwear users, the probability of medial tibiofemoral cartilage failure was significantly greater in conventional (habitual = 47.19% and non-habitual = 50.00%) compared to minimal footwear (habitual = 33.18% and non-habitual = 32.81%) users. The observations from this investigation show that compared to minimal footwear, conventional footwear appears to have a negative influence on medial tibiofemoral cartilage health.

Sarcopenia: Body Composition and Gait Analysis.

Background: Age-induced sarcopenia negatively affects walking stability and increases the risk of falls, which is the leading cause of accidental death in the elderly. Objective: This study aimed to analyze and contrast body composition and gait characteristics in those with sarcopenia in relation to healthy controls to shed some light on the prevention of falls in elderly patients with sarcopenia. Materials and Methods: In this study, 68 community dwellers were scanned by the Hologic QDR-4500A Dual-energy X-ray absorptiometry (DXA). The appendicular lean mass index (ALMI) results were used to distinguish the normal participants from those with sarcopenia: 24 in the sarcopenia group, and 44 into the normal group. The participants were asked to undergo gait analysis on a plantar pressure measurement system. Statistical analysis was conducted to contrast both groups' gait and butterfly parameters from their gait test, and then a gait forward dynamics method was performed to quantify the analysis for both groups. Results: The ALMI of the female was not related to their age (r = 0.06) while that of the male was weakly related (r = 0.17). Body mass index (BMI) from both groups was normal, although with a statistically greater BMI from the normal group compared with sarcopenia (p < 0.001). Greater values and significant differences were found in step length and stride length from the normal elderly group (p < 0.01), and so was the length of the gait line and single support line (p < 0.05). Gait forward dynamics analysis results showed no motor neural or musculoskeletal disorders in their gait performance from the sarcopenia group. Conclusion: For the elderly, age did not largely affect the ALMI, BMI, or T-score, but BMI and ALMI were strongly correlated. In this study, significant differences were found in certain gait parameters between the elderly with sarcopenia and the normal elderly, which were related to absolute muscle strength, suggesting that sarcopenia was a disease mainly caused by decreased muscle mass. In addition, when abnormities were identified in step length, stride length, length of gait line, or length of single support line, it is proposed to take a DXA scan to confirm whether the elderly suffer from sarcopenia.

Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype.

Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited. Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome sequencing, whole genome bisulfite sequencing, RNA sequencing, and immunohistochemistry. The data were further examined using public GBM databases and GBM cell line. Results: Analysis on genetic data confirmed common features of GBM, including gain of chr.7 and loss of chr.10, loss of critical tumor suppressors, high frequency of PDGFA and EGFR amplification. Through profiling DNA methylome of individual tumor foci, we found that promoter methylation status of genes involved in detection of chemical stimulus, immune response, and Hippo/YAP1 pathway was significantly changed in mGBM. Although both CNV and promoter methylation alteration were involved in heterogeneity of different tumor foci from same patients, more CNV events than promoter hypomethylation events were shared by different tumor foci, implying CNV were relatively earlier than promoter methylation alteration during evolution of different tumor foci from same mGBM. Moreover, different tumor foci from same mGBM assumed different molecular subtypes and mesenchymal subtype was prevalent in mGBM, which might explain the worse prognosis of mGBM than single GBM. Interestingly, we noticed that LIF and CCL2 was tightly correlated with mesenchymal subtype tumor focus in mGBM and predicted poor survival of GBM patients. Treatment with LIF and CCL2 produced mesenchymal-like transcriptome in GBM cells. Conclusions: Together, our work herein comprehensively profiled multi-omics features of mGBM and emphasized that components of extracellular microenvironment, such as LIF and CCL2, contributed to the evolution and prognosis of tumor foci in mGBM patients.

Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage.

BACKGROUND: Alzheimer's disease (AD) and glioblastoma are the most common and devastating diseases in the neurology and neurosurgery departments, respectively. Our previous research reports that the AD-related protein Presenilin1 represses cell proliferation by inhibiting the Wnt/ß-catenin pathway in glioblastoma. However, the function of Presenilin1 and the underlying mechanism need to be further investigated. METHODS: The correlations of two genes were conducted on the R2 microarray platform and CGGA. Wound healing, Transwell assays and glioblastoma transplantation were performed to detect invasion ability. Phalloidin staining was employed to show cell morphology. Proximity ligation assays and protein docking assays were employed to detect two protein locations. We also employed western blotting to detect protein expression. RESULTS: We found that Presenilin1 clearly repressed the migration, invasion and mesenchymal transition of glioblastoma cells. Intriguingly, we observed that the expression of Presenilin1 was positively correlated with Sortilin, which is identified as a pro-invasion molecule in glioma. Furthermore, Presenilin1 interacted with Sortilin at the transmembrane domain and repressed Sortilin expression by cleaving it in glioblastoma cells. First, we found that Sortilin introduced the function of Presenilin1 in phosphorylating ß-catenin and repressing invasion in glioblastoma cells. Last, Presenilin1 stimulation sharply suppressed the invasion and mesenchymal transition of glioblastoma in mouse subcutaneous and intracranial transplantation models. CONCLUSIONS: Our study reveals that Sortilin mediates the regulation of ß-catenin by Presenilin1 and transduces the anti-invasive function of Presenilin1, which may provide novel therapeutic targets for glioblastoma treatment. Video Abstract.

Effects of Mixing Garlic Skin on Fermentation Quality, Microbial Community of High-Moisture Pennisetum hydridum Silage.

Garlic skin, a by-product of garlic processing, was supposed to improve the fermentation quality of high-moisture silages because of its low moisture content and active compounds. Thus, fermentation and microbial characteristics of high-moisture Pennisetum hydridum ensiled with the addition of 0, 10, 20, and 30 wt% garlic skin (on a fresh matter basis) were analyzed during a 60-days fermentation. Results showed that the addition of garlic skin increased the dry matter content and lactic acid production, and decreased the pH and ammonia-N content of the silage. Adding garlic skin changed the relative abundance of bacterial communities with an increase in Lactobacillus and a decrease in Clostridium relative abundance. In conclusion, co-ensiling of high-moisture Pennisetum hydridum with garlic skin could be a simple approach to improve the silage quality and nutrients preservation.

Sodium Butyrate More Effectively Mitigates the Negative Effects of High-Concentrate Diet in Dairy Cows than Sodium ß-Hydroxybutyrate via Reducing Free Bacterial Cell Wall Components in Rumen Fluid and Plasma.

The present study was aimed at investigating the effects of sodium butyrate and sodium ß-hydroxybutyrate on lactation and health of dairy cows fed a high-concentrate (HC) diet. Eighty mid-lactation dairy cows with an average milk yield of 33.75 ± 5.22 kg/d were randomly allocated to four groups (n = 20 per group) and were fed either a low-concentrate (LC) diet, a HC diet, the HC diet with 1% sodium butyrate (HCSB), or the HC diet with 1% sodium ß-hydroxybutyrate (HCHB). The feeding trial lasted for 7 weeks, with a 2-week adaptation period and a 5-week measurement period, and the trial started from 96 ± 13 d in milk. Sodium butyrate supplementation delayed the decline in milk production and improved milk synthesis efficiency and milk fat content. Additionally, it decreased the proinflammatory cytokines and acute phase proteins (APPs) in plasma, the leucocytes in blood, the somatic cell count (SCC) in milk, and the gene expression of pattern recognition receptors (PRRs) and proinflammatory cytokines in the mammary gland, due to decreasing the contents of bacterial cell wall components (lipopolysaccharide, LPS; peptidoglycan, PGN; and lipoteichoic acid, LTA) in the rumen and plasma, compared with the HC diet. Sodium ß-hydroxybutyrate supplementation also improved milk yield, milk synthesis efficiency and milk fat content and partially reduced the adverse effects caused by the HC diet, but it had no effect on decreasing bacterial cell wall components in the rumen and plasma, compared with the HC diet. Collectively, both sodium butyrate and sodium ß-hydroxybutyrate mitigated the negative effects of HC diet on lactation and health of dairy cows, with sodium butyrate being more effective than sodium ß-hydroxybutyrate.

Rediscovering Potential Molecular Targets for Glioma Therapy Through the Analysis of the Cell of Origin, Microenvironment and Metabolism.

Gliomas are the most common type of malignant brain tumors. Despite significant medical advances, gliomas remain incurable and are associated with high mortality. Although numerous biomarkers of diagnostic value have been identified and significant progress in the prognosis of the outcome has been made, the treatment has not been parallelly improved during the last three decades. This review summarizes and discusses three aspects of recent discoveries related to glioma, with the objective to highlight the advantages of glioma-specific drugs targeting the cell of origin, microenvironment, and metabolism. Given the heterogeneous nature of gliomas, various cell populations have been implicated as likely sources of the tumor. Depending on the mutation(s) acquired by the cells, it is believed that neural stem/progenitor cells, oligodendrocyte progenitor cells, mature neurons, and glial cells can initiate cell transformation into a malignant phenotype. The level of tumorigenicity appears to be inversely correlated with the maturation of a given cell population. The microenvironment of gliomas includes non-cancer cells such as immune cells, fibroblasts, and cells of blood vessels, as well as secreted molecules and the extracellular matrix, and all these components play a vital role during tumor initiation and progression. We will discuss in detail how the tumor microenvironment can stimulate and drive the transformation of non-tumor cell populations into tumor-supporting cells or glioma cells. Metabolic reprogramming is a key feature of gliomas and is thought to reflect the adaptation to the increased nutritional requirements of tumor cell proliferation, growth, and survival. Mutations in the IDH gene can shape metabolic reprogramming and may generate some vulnerabilities in glioma cells, such as abnormal lipid metabolism and sensitivity to endoplasmic reticulum stress (ERS). We will analyze the prominent metabolic features of malignant gliomas and the key pathways regulating glioma metabolism. This review is intended to provide a conceptual background for the development of glioma therapies based on the properties of tumor cell populations, microenvironment, and metabolism.

Physical investigation of acoustic waves induced by the oscillation and collapse of the single bubble.

The objective of this paper is to apply both experimental and numerical methods to investigate acoustic waves induced by the oscillation and collapse of a single bubble. In the experiments, the schlieren technique is used to capture the temporal evolution of the bubble shapes, and the corresponding acoustic waves. The results are presented for the single bubble generated by a low-voltage bubble generator in the free field of water. During the numerical simulations, a three-dimensional (3D) weakly compressible model is introduced to investigate the single bubble dynamics, including the generation and propagation of acoustic waves. The results show that (1) Compression wave, rarefaction wave and shock wave are generated during expansion stage, collapse stage and rebound stage of the bubble respectively. (2) Compression waves are induced by the rapid expansion of the bubble and eventually steepen into one shock wave propagating outward in the liquid, then another strong shock wave is emitted at the final collapse stage. The velocity and pressure of the liquid field increases after the shock wave. (3) Rarefaction waves are generated during the collapse stage due to the contraction of the bubble. The rarefaction wave reduces the liquid pressure and its spatial distribution is dispersive. The pressure of these acoustic waves and their effect on the liquid velocity attenuate with the increase of propagation distance.

A systematic review of multifocal and multicentric glioblastoma.

Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is more genetically heterogeneous, aggressive and resistant to chemoradiotherapy than unifocal GBM, and has a worse prognosis. There is no international consensus on the treatment of multiple GBM. This review discusses some paradigms of multiple GBM and focuses on the heterogeneity spread pathway, imaging diagnosis, pathology, molecular characterization and prognosis of multifocal and multicentric GBM. Several promising therapeutic methods of multiple GBM are also recommended.

Combined use of microwave ablation and cell immunotherapy induces nonspecific immunity of hepatocellular carcinoma model mice.

Microwave ablation (MWA) has been widely used in the treatment of solid tumors. Studies have been less conducted on the efficacy of MWA used with cell immunotherapy in treating hepatocellular carcinoma (HCC). The current study aimed at exploring the efficacy of MWA in combination with cell immunotherapy in treating HCC. Hepa1-6 HCC mice were treated by MWA, blockade, or the combined therapy (MWA used with blockade), or left untreated. Survival rates of the mice were plotted by Kaplan-Meier Curve, followed by log-rank test. 25 days after the operation, surviving mice were monitored for tumor recurrence, and tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were performed to detect the numbers of CD4+ and CD8+ cells in the tumors and spleens of mice. The expressions of related cytokines were detected and measured by ELISPOT and ELISA. The results showed that MWA combined with anti-PD-1/anti-CTLA-4 not only increased the survival time, protected the mice against tumor recurrence, but also enhanced the intratumoral infiltration of cytotoxic T lymphocyte and systemic T-cell immune responses induced by MWA through activation of synergistically specific antitumor immunity. In addition, the combined therapy increased T-helper 1 cell (Th1-type) cytokines, but reduced Th2-type cytokines, resulting in the polarization of Th1 cells. T-cell immune responses of HCC cells were activated by MWA. In addition, the combined therapy of MWA and anti-PD-1/anti-CTLA-4 induced Th1-type immune response, and showed specific antitumor immunity.

Integrative transcriptome analysis identified a BMP signaling pathway-regulated lncRNA AC068643.1 in IDH mutant and wild-type glioblastomas.

Glioblastomas (GBMs) are classified into isocitrate dehydrogenase (IDH) mutant (IDH MT) and wild-type (IDH WT) subtypes, and each is associated with distinct tumor behavior and prognosis. The present study aimed to investigate differentially expressed long non-coding (lnc)RNAs and mRNAs between IDH MT and IDH WT GBMs, as well as to explore the interaction and potential functions of these RNAs. A total of 132 GBM samples with RNA profiling data (10 IDH MT and 122 IDH WT cases) were obtained from The Cancer Genome Atlas, and 62/78 and 142/219 up/downregulated lncRNAs and mRNAs between IDH MT and IDH WT GBMs were identified, respectively. Multivariate Cox analysis of the dysregulated lncRNAs/mRNAs identified three-lncRNA and fifteen-mRNA signatures with independent prognostic value, indicating that these RNAs may serve roles in determining distinct tumor behaviors and prognosis of patients with IDH MT/WT GBMs. Functional analysis of the three lncRNAs revealed that they were primarily associated with cell stemness or differentiation. Pearson's correlation analysis revealed that the protective lncRNA AC068643.1 was significantly positively correlated with two key bone morphogenetic protein (BMP) signaling-associated mRNAs, Bone morphogenetic protein 2 (BMP2) and Myostatin (MSTN), from the 15 mRNAs. Further in vitro studies demonstrated that BMP2 and MSTN directly stimulated AC068643.1 expression. In conclusion, the present study identified a BMP signaling pathway-regulated lncRNA AC068643.1, which may contribute to the different tumor behaviors observed between IDH MT and IDH WT GBMs.

Dynamic behavior of a single bubble between the free surface and rigid wall.

The objective of this paper is to apply high-speed photography and schlieren method to investigate the bubble dynamics between the free surface and a rigid wall. The temporal evolution of the bubble shape and the free surface motion are recorded by two synchronous high-speed cameras. Experiments are carried out for a single bubble generated at various normalized stand-off distances from bubble center to the free surface and to the rigid wall. The results show that (1) three distinctive patterns are identified with the morphology of the bubble and free surface, namely single toroidal bubble without spike (STB), single toroidal bubble with a spike (STBS) and double toroidal bubbles with a spike (DTBS). (2) The dynamic characteristics of the bubble at collapse and rebound stage vary evidently at different patterns, including the bubble shape variations and free surface motion. In detail, the schlieren images show the formation and propagation of shock waves, which explains the radiative process of bubble collapse energy. (3) Qualitative comparisons are carried out for the bubble and free surface at the same pattern. And quantitative analyses are conducted for the jet velocity, bubble collapse position, bubble collapse time and spike height, etc. for different values of bubble-rigid wall distance.