Diaphragm thickness on computed tomography for nutritional assessment and hospital stay prediction in critical COVID-19.

BACKGROUND AND OBJECTIVES: To evaluate the significance of diaphragm thickness (DT) in assessing the nutritional status and predicting the length of hospital stay (LOS) of patients with COVID-19. METHODS AND STUDY DESIGN: The data of 212 patients with severe and critical COVID-19 in Wuhan, China, were retrospectively analyzed. Computed tomography (CT)-obtained DT was measured in cross-sectional images of the mediastinal window at the level of the outlet of the celiac trunk at admission and at 2 weeks, then the rate of change in DT(RCDT) at 2 weeks was calculated. Nutritional risk and malnutrition were evaluated at admission. RESULTS: A total of 91 patients were involved in the study. The mean DT was 3.06±0.58 mm (3.15±0.63 mm in male and 2.93±0.50 mm in female). DT was significantly negatively correlated with malnutrition based on Global Leadership Initiative on Malnutrition (GLIM) criteria (r=-0.324, p=0.002), Nutritional Risk Screening 2002 (NRS-2002) score (r=-0.364, p=0.000) and the Malnutrition Universal Screening Tool (MUST) score (r=-0.326, p=0.002) at admission. For the prediction of LOS ≥4 weeks in patients with COVID-19, the area under the ROC curve (AUC) of the RCDT at 2 weeks was 0.772, while the AUCs of DT, NRS-2002, MUST and Nutrition Risk in Critically Ill scores at admission were 0.751, 0.676, 0.638 and 0.699 respectively. According to the model of multiple linear regression analysis, the DT at admission (ß=-0.377, p=0.000), RCDT at 2 weeks (ß =-0.323, p=0.001), and mechanical ventilation (ß=0.192, p=0.031) were independent risk factors contributed to LOS. CONCLUSIONS: CT-obtained DT can be used as a dynamic assessment tool for evaluating the nutritional status of patients in isolation wards for COVID-19.

Application of a novel artificial perfusate based on oxygen-carrying nanoparticles in normothermic machine perfusion for porcine liver preservation after cardiac death.

OBJECTIVE: To investigate the efficacy of a novel artificial perfusate based on oxygen-carrying perfluoronaphthalene-albumin nanoparticles in normothermic machine perfusion (NMP) for preservation of porcine liver donation after cardiac death. METHODS: Artificial perfusate with perfluoronaphthalene-albumin nanoparticles was prepared at 5% albumin (w/v) and its oxygen carrying capacity was calculated. The livers of 16 Landrace pigs were isolated after 1 h of warm ischemia, and then they were divided into 4 groups and preserved continuously for 24 h with different preservation methods: cold preservation with UW solution (SCS group), NMP preservation by whole blood (blood NMP group), NMP preservation by artificial perfusate without nanoparticles (non-nanoparticles NMP group) and NMP preservation by artificial perfusate containing nanoparticles (nanoparticles NMP group). Hemodynamics, tissue metabolism, biochemical indices of perfusate and bile were monitored every 4 h after the beginning of NMP. Liver tissue samples were collected for histological examination (HE and TUNEL staining) before preservation, 12 h and 24 h after preservation. RESULTS: The oxygen carrying capacity of nanoparticles in 100 mL artificial perfusate was 6.94 µL/mmHg (1 mmHg=0.133 kPa). The hepatic artery and portal vein resistance of nanoparticles NMP group and blood NMP group remained stable during perfusion, and the vascular resistance of nanoparticles NMP group was lower than that of blood NMP group. The concentration of lactic acid in the perfusate decreased to the normal range within 8 h in both nanoparticles NMP group and blood NMP group. There were no significant differences in accumulated bile production, alanine aminotransferase and aspartate aminotransferase in perfusate between nanoparticles NMP group and blood NMP group (all P>0.05). After 24 h perfusion, the histological Suzuki score in blood NMP group and nanoparticles NMP group was lower than that in SCS group and non-nanoparticles NMP group (all P<0.05), and the quantities of TUNEL staining positive cells in blood NMP group and non-nanoparticles NMP group was higher than those in nanoparticles NMP group and SCS group 12 h and 24 h after preservation (all P<0.05). CONCLUSION: Artificial perfusate based on oxygen-carrying nanoparticles can meet the oxygen supply requirements of porcine livers donation after cardiac death during NMP preservation, and it may has superiorities in improving tissue microcirculation and alleviating ischemia-reperfusion injury.

Association of Monocyte-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios With Persistent Critical Illness in Patients With Severe Trauma.

BACKGROUND: Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio are reported to reflect the inflammation and immune status in critically ill patients, but their role in severe trauma patients with persistent critical illness remains to be elucidated. OBJECTIVE: We aimed to evaluate the relationship of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio with persistent critical illness in severe trauma patients. METHODS: In a single-center retrospective cohort study, persistent critical illness was defined as intensive care unit length of stay of more than 10 days. Monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were computed individually and categorized into 3 tertiles. Logistic regression analysis was used to assess the relationship of monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with persistent critical illness. Receiver operating characteristic curves and the Youden index were used to evaluate the discriminatory threshold of persistent critical illness. RESULTS: A total of 851 eligible patients were enrolled in the study: 328 patients with persistent critical illness and 523 without. The median levels of maximum neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio during intensive care unit stay were all higher in patients with persistent critical illness than in those without (11.46 vs. 9.13, p < .001 and 0.62 vs. 0.46, p < .001). Multivariate analysis revealed that the second (≥0.385, <0.693) and third (≥0.693) maximum monocyte-to-lymphocyte ratio tertiles were significantly associated with persistent critical illness after adjusting for confounding factors (odds ratio: 1.89, 95% confidence interval: 1.10-3.26, p = .021 and odds ratio 2.69, 95% confidence interval: 1.44-5.02, p = .002, respectively), whereas maximum neutrophil-to-lymphocyte ratio was not significantly correlated with persistent critical illness. The area under the curve for the maximum monocyte-to-lymphocyte ratio was 0.63 (95% confidence interval: 0.59-0.67), and the optimal cutoff was 0.65 for persistent critical illness. CONCLUSION: A high maximum monocyte-to-lymphocyte ratio during intensive care unit stay was independently related to persistent critical illness following severe trauma, although with limited sensitivity and specificity.

Temperature Variability Does Not Attenuate the Beneficial Effects of Therapeutic Hypothermia on Cellular Apoptosis and Endoplasmic Reticulum Stress in the Cerebral Cortex of a Swine Cardiac Arrest Model.

BACKGROUND: Endoplasmic reticulum stress (ERS) plays a vital role in mediating apoptosis in the brain following cardiac arrest (CA). Studies have shown that therapeutic hypothermia (TH) provides neuroprotection through anti-apoptosis; however, the effects of temperature variability in TH on the brain remain unclear. In this study, we investigated the different effects of temperature variability through extracorporeal membrane oxygenation on apoptosis and ERS in the brain following CA. METHODS: Eighteen male domestic pigs underwent 6-min duration of no-flow induced by ventricular fibrillation. Extracorporeal cardiopulmonary resuscitation was then performed, and the return of spontaneous circulation (ROSC) was achieved. The animals were randomly assigned to the following groups: normothermia, non-temperature variability, and temperature variability. TH (core temperature, 33-35 °C) was maintained for 24 h post-ROSC, and the animals were rewarmed for 8 h. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry for Bax and Bcl-2 transcripts and proteins, respectively, were used to investigate apoptosis in the cerebral cortex. Expression levels of the ERS molecules, GRP78 and CHOP, were also detected by qRT-PCR, and cellular morphology was evaluated using transmission electron microscopy. RESULTS: qRT-PCR and immunohistochemistry results revealed that TH significantly increased the expression levels of Bcl-2 and GRP78 and decreased that of Bax and CHOP than under normothermia conditions. Compared to the non-temperature variability group, temperature variability did not decrease the expression levels of Bcl-2 and GRP78 and not increase the levels of Bax and CHOP. Endoplasmic reticulum ultrastructural changes were significantly improved under TH. No statistical difference was observed between the temperature variability and non-temperature variability groups. CONCLUSION: TH can reduce neuronal apoptosis by ERS, while temperature variability does not attenuate this beneficial effect.

Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

PURPOSE: Chlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia. METHODS: Nine cases of severe psittacosis pneumonia were diagnosed using mNGS. Retrospective analysis of the data on disease progression, new diagnosis tool, treatments, and outcomes, and the findings were summarised. RESULTS: Frequent symptoms included chills and remittent fever (100%), cough and hypodynamia (100%), and headache and myalgia (77.8%). All patients were severe psittacosis pneumonia developed respiratory failure, accompanied by sepsis in 6/9 patients. mNGS takes 48-72 h to provide the results, and help to identify diagnosis of psittacosis. Laboratory data showed normal or slightly increased leucocytes, neutrophils, and procalcitonin but high C-reactive protein levels. Computed tomography revealed air-space consolidation and ground-glass opacity, which began in the upper lobe of one lung, and spread to both lungs, along with miliary, nodular, or consolidated shadows. One patient died because of secondary infection with Klebsiella pneumoniae, while the other eight patients experienced complete recoveries. CONCLUSIONS: The use of mNGS can improve accuracy and reduce the delay in diagnosis of psittacosis. Severe psittacosis pneumonia responds well to the timely use of appropriate antibiotics.

Three-Dimensional Ameliorated Biologics Elicit Thymic Renewal in Tumor-Bearing Hosts.

Cancer-initiating/sustaining stem cell subsets (CSCs) have the potential to regenerate cancer cell populations and are resistant to routine therapeutic strategies, thus attracting much attention in anticancer research. In this study, an innovative framework of endogenous microenvironment-renewal for addressing such a dilemma has been just developed. CSCs in three-dimensional multipotent spheroid-engineered biologics were prepared with 150 Gy radiation and inoculated into 15-mo-old BALB/c and C57BL/6 mice bearing diverse advanced tumors covering Mammary 4T1, liver Hepa, lung LL/2, and colon C26 tumors and distant metastases. Subsequently, the systematic microenvironment of tumor-bearing hosts was rapidly remodeled to resettle thymic cortex and medulla rudiment as an endogenous foxn1-thymosin reprogramming TCR-repertoire for resetting MHC-unrestricted multifunction renewal. Postrenewal Vγ4γδT-subsets would bind and lead migrating CSCs into apoptosis. Moreover, TCR repertoire multifunction renewal could reverse tumor metastases from tumoricidal resistance into eventual regression as a blockade of cancer-sustaining Bmi-1/Nanog-Oct4-Sox2 renewal loop with sequent multivalent depletion of both migrating/in situ CSCs and non-stem terminal cancer cell subsets. This study represents a promising start to set up a generalizable strategy of three-dimensional biologics evoking an endogenous integral microenvironment into pluripotent renewal versus advanced cancer.

Clinical Features of Fatal Pandemic Influenza A/H1N1 Infection Complicated by Invasive Pulmonary Fungal Infection.

BACKGROUND: Severe pneumonia caused by influenza virus infection can be secondary to invasive pulmonary fungal (IPF) infection. OBJECTIVES: This study aimed to summarize the incidence of IPF infection secondary to influenza virus infection and further explore its etiologic mechanism and high-risk factors. METHODS: All adult patients with confirmed influenza A (H1N1) virus infection admitted to the intensive care units (ICUs) of Nanjing Drum Hospital from November 2017 to March 2018 were retrospectively selected. The differences in baseline factors, risk factors, immune function and outcome parameters were studied between patients with and without IPF. RESULTS: Of the 19 critically ill patients with H1N1 infection, 11 (57.9%) developed IPF infection after 7 days of ICU admission. Two patients had proven and nine probable IPF infection. A difference in human leukocyte antigen-DR isotype (△HLA-DR; day 7-day 1) was found between the two groups. △HLA-DR (day 7-day 1) was higher in patients with no IPF infection than in those with IPF infection [(14.52 ± 14.21)% vs ( - 11.74 ± 20.22)%, P = 0.019]. The decline in HLA-DR indicated impaired immune function secondary to fungal infection in patients with H1N1 infection. CONCLUSIONS: IPF infection was diagnosed in 57.9% of critically ill patients with H1N1 virus infection after a median of 7 days following ICU admission. A continuous decline in immune function could lead to the development of IPF infections. Dynamic monitoring of immune function may help in the early detection of IPF infection.

Clinical features of fatal severe fever with thrombocytopenia syndrome that is complicated by invasive pulmonary aspergillosis.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) has been prevalent in parts of Asia during recent years. However, SFTS with invasive pulmonary aspergillosis (IPA) is rare, and it is important to understand its clinical features. MATERIALS AND METHODS: Total four cases of SFTS with IPA are reviewed and detailing the disease progression, treatment options, and prognosis were summarized and analyzed. RESULTS: The patients with SFTS-associated IPA first presented with fever, gastrointestinal symptoms, thrombocytopenia, leukopenia, and multiple organ failure. After 1-2 weeks, the patients developed mild polypnea and wheezing rales, and quickly developed dyspnea and respiratory failure. Tracheal intubation was usually performed, but did not relieve the intractable airway spasm and pulmonary ventilation failure. Bronchoscopy confirmed that the antifungal treatment was ineffective and the aspergillosis had worsened. All patients died of type 2 respiratory failure caused by continued airway obstruction and spasticity. CONCLUSIONS: Given the high mortality rate in this series, there is a need for increased awareness of SFTS-associated IPA. Additional examinations should be performed in these cases, and early-stage antifungal treatment with organ support may be helpful.

IL-37 ameliorates the inflammatory process in psoriasis by suppressing proinflammatory cytokine production.

IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A-transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A-transgenic mice were treated with plasmid coding human IL-37 sequence-formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: clinical experience and literature review.

AIM: To analyze the clinicopathological features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCC) in our institution. MATERIALS & METHODS: We screened 983 RCC specimens. TFE3 immunohistochemical staining and FISH assay confirmed 22 Xp11.2 RCCs out of 65 suspicious cases. Clinicopathological and treatment outcomes of 22 patients were retrospectively analyzed. RESULTS: In total, 22 patients included 13 females and nine males with a mean age of 27 years. Ten patients showed gross hematuria. Treatments included surgeries, immunotherapy and molecular-targeted therapy. Seven cases were at stage III/IV and four cases had tumor thrombosis or distant metastasis. During a median follow-up of 34 months, 19 patients were alive while three died of distant metastasis. CONCLUSION: Xp11.2 RCC is rare and FISH proved a useful diagnostic tool. Surgical resection achieved favorable outcome for early disease. Adult patients at advanced stage had poorer outcomes even with postoperative adjuvant therapy.

Xp11.2 translocation renal cell carcinomas in young adults.

BACKGROUND: Little is known about the biological behavior of Xp11.2 translocation renal cell carcinomas (RCCs) as few clinical studies have been performed using a large sample size. METHODS: This study included 103 consecutive young adult patients (age ≤ 45 years) with RCC who underwent partial or radical nephrectomy at our institution from 2008 to 2013. Five patients without complete clinical data were excluded. Of the 98 remaining patients, 16 and 82 patients were included in the Xp11.2 translocation and non-Xp11.2 translocation groups, respectively. Clinicopathologic data were collected, including age, gender, tumor size, laterality, symptoms at diagnosis, surgical procedure, pathologic stage, tumor grade, time of recurrence and death. RESULTS: Xp11.2 translocation RCCs were associated with higher tumor grade and pathologic stage (P < 0.05, Fisher's exact test). During the median follow-up of 36 months (range: 3-71 months), the number of cancer-related deaths was 4 (4.9%) and 3 (18.7%) in the non-Xp11.2 translocation and Xp11.2 translocation groups, respectively. The Kaplan-Meier cancer specific survival curves revealed a significant difference between non-Xp11.2 translocation RCCs and Xp11.2 translocation RCCs in young adults (P = 0.042). CONCLUSIONS: Compared with non-Xp11.2 translocation RCCs, the Xp11.2 translocation RCCs seemingly showed a higher tumor grade and pathologic stage and have similar recurrence-free survival rates but poorer cancer-specific survival rates in young adults.

Effective inhibition of melanoma tumorigenesis and growth via a new complex vaccine based on NY-ESO-1-alum-polysaccharide-HH2.

BACKGROUND: A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2. METHODS: The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated. RESULTS: The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma. CONCLUSIONS: Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.

VEGF-D-induced draining lymphatic enlargement and tumor lymphangiogenesis promote lymph node metastasis in a xenograft model of ovarian carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF)-D has been shown to promote lymph node metastasis in several cancers. Although generally overexpressed in ovarian carcinoma, its role in nodal dissemination of this cancer is unclear. To clarify the role of VEGF-D and the underlying molecular mechanisms, we investigated the function of VEGF-D using a mouse xenograft model of ovarian cancer. METHODS: Human ovarian serous adenocarcinoma SKOV3 cells were transfected with VEGF-D recombinant plasmid DNA, or with control vectors. The cells were injected subcutaneously into the footpads of nude mice. Tumor growth was evaluated weekly. Draining lymphatics were observed grossly with Evan's blue lymphangiography. Tumoral lymphatics were delineated with both Evan's blue and LYVE-1 immunostaining. Tumor metastases to lymph nodes were evaluated by H&E and CA125/CD40 staining. Expression of VEGF-D in primary tumors and levels of CA125 in involved lymph nodes were examined by immunohistochemistry. Tumor cell apoptosis was analyzed by Hoechst dyeing. RESULTS: Mice bearing VEGF-D overexpressing xenografts showed a significantly higher rate of lymph node metastasis and markedly greater tumor volume compared with the controls. The functional lymphatic vessels were denser and enlarged in marginal and central tumor portions. Additionally, higher CA125 expression was observed in the involved lymph nodes. Mice bearing VEGF-D overexpressing xenografts also exhibited a markedly lower apoptotic index compared with the controls. CONCLUSIONS: Our data demonstrate the important role of VEGF-D in promoting lymph node metastasis by increasing tumor lymphangiogenesis, stimulating draining lymphatic vessel formation, and enhancing tumor invasiveness. Our findings show that VEGF-D can be a promising therapeutic target for ovarian cancer.

Suppression of peritoneal tumorigenesis by placenta-derived mesenchymal stem cells expressing endostatin on colorectal cancer.

MSCs-based therapy for cancer is a relatively new but rapidly growing area of research. Human term placenta, an attractive source of MSCs (PMSCs), appears to have great advantage due to its easy access without invasive procedures, its lack of ethical issues and its high-throughput and young age. In the present study, we isolated MSCs from placenta and characterized their morphology and differentiation capacities. We next investigated the underlying antitumor effects and the potential mechanism of PMSCs to express endostatin using adenoviral transduction (Ad-Endo) in a colorectal peritoneal carcinomatosis (CRPC) mouse model. For in vitro experiments, the migratory potential of Ad-Endo-PMSCs towards tumor cells was demonstrated using a double-chamber assay, and the anti-angiogenesis ability of endostatin from engineered PMSCs was evaluated using the tube formation assay. For the in vivo study, mice harboring CT26 colorectal cancer indicated a significant reduction in tumor nodules and a prolongation of survival following Ad-Endo-PMSCs therapy. These observations were associated with significantly decreased tumor cell proliferation and blood vessel counts as well as increased tumor cell apoptosis. These data suggested the potential of PMSCs-based gene therapy for the targeted delivery of therapeutic proteins in cancer.

[Application of polyclonal break-apart probes in the diagnosis of Xp11.2 translocation renal cell carcinoma].

OBJECTIVE: To explore the value of self-designed fluorescent in situ hybridization (FISH) polyclonal break-apart probes specific for TFE3 gene in the diagnosis of Xp11.2 translocation renal cell carcinoma. METHODS: All tissue samples were collected from 2006 to 2013, including Xp11.2 translocation renal cell carcinoma (n = 10), renal clear cell carcinoma (n = 10) and renal papillary cell carcinoma (n = 10). FISH was conducted for paraffin-embedded tumor tissue sections with probes. The types of fluorescence were observed by fluorescent microscopy to determine the existence or non-existence of translocated TFE3 gene. RESULTS: All sections were successfully probed. The split red and green signals within a single nucleus were detected simultaneously in 9 cases of Xp11.2 translocation renal cell carcinoma as diagnosed by traditional pathological and immunohistochemical methods. And it was consistent with the initial diagnosis. Detection of fusion signal in 1/10 and negative FISH result did not conform to the initial diagnosis. The fluorescent types of renal clear cell carcinoma and renal papillary cell carcinoma were all fusion signals. FISH tests were negative for renal clear and papillary cell carcinomas. CONCLUSIONS: Xp11.2 translocation renal cell carcinomas diagnosed by traditional pathological and immunohistochemical methods are sometimes misdiagnosed. Detecting the translocation of TFE3 gene with FISH polyclonal break-apart probes is both accurate and reliable for diagnosing Xp11.2 translocation renal cell carcinoma.

Application of CUSA Excel ultrasonic aspiration system in resection of skull base meningiomas.

BACKGROUND: Here, we introduced our short experience on the application of a new CUSA Excel ultrasonic aspiration system, which was provided by Integra Lifesciences corporation, in skull base meningiomas resection. METHODS: Ten patients with anterior, middle skull base and sphenoid ridge meningioma were operated using the CUSA Excel ultrasonic aspiration system at the Neurosurgery Department of Shanghai Huashan Hospital from August 2014 to October 2014. There were six male and four female patients, aged from 38 to 61 years old (the mean age was 48.5 years old). Five cases with tumor located at anterior skull base, three cases with tumor on middle skull base, and two cases with tumor on sphenoid ridge. RESULTS: All the patents received total resection of meningiomas with the help of this new tool, and the critical brain vessels and nerves were preserved during operations. All the patients recovered well after operation. CONCLUSIONS: This new CUSA Excel ultrasonic aspiration system has the advantage of preserving vital brain arteries and cranial nerves during skull base meningioma resection, which is very important for skull base tumor operations. This key step would ensure a well prognosis for patients. We hope the neurosurgeons would benefit from this kind of technique.

Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development.

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

[Predictive value of lipoproteins on progression to chronic critical illness in intensive care unit patients].

OBJECTIVE: To explore the predictive value of lipoproteins on the progression of critically ill patients to chronic critical illness (CCI). METHODS: A retrospective cohort study was conducted to analyze clinical data of patients admitted to the intensive care unit (ICU) of Nanjing Drum Tower Hospital from January 1, 2020, to December 31, 2022. The levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apolipoproteins (ApoA-I, ApoB) at 1, 3, 7, 14 and 21 days after admission to ICU were collected. The progression to CCI was recorded. CCI was defined as the length of ICU stay ≥14 days with sustained organ dysfunction [sequential organ failure assessment (SOFA) score ≥2]. Differences in lipoprotein levels between the patients with and without CCI were compared. Multivariate Logistic regression was used to analyze risk factors for critically ill patients progressing to CCI. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of lipoproteins on critically ill patients progressing to CCI. RESULTS: A total of 200 patients were enrolled in the final analysis. 137 patients (68.5%) progressed to CCI, and 63 patients (31.5%) did not. The lipoprotein indicators in the CCI group showed a decrease after the acute phase, while the lipoprotein indicators in the non-CCI group showed an increase. The levels of HDL, LDL, ApoA-I, and ApoB at various time points in the CCI group were significantly lower than those in the non-CCI group. HDL at 7 days in the CCI group was significantly lower than that in the non-CCI group [mmol/L: 0.44 (0.31, 0.61) vs. 0.67 (0.49, 0.75), P < 0.01]. Multivariate Logistic regression analysis showed that 7-day HDL was an independent risk factor for critically ill patients progressing to CCI [odds ratio (OR) = 0.033, 95% confidence interval (95%CI) was 0.004-0.282, P = 0.002]. ROC curve analysis showed that the area under the ROC curve (AUC) of 7-day HDL for predicting critically ill patients progressing to CCI was 0.702, with a 95%CI of 0.625-0.779, P < 0.001. When the optimal cut-off value was 0.59 mmol/L, the sensitivity was 69.8%, and the specificity was 72.4%. CONCLUSIONS: The low level of lipoproteins is closely related to the progression of critically ill patients, and 7-day HDL has a certain predictive value for critically ill patients progressing to CCI. Continuously observation of the change trend of lipoprotein level is helpful to judge the progression of CCI in critically ill patients.

Early changes in GMRP1 after intracerebral hemorrhage: involvement in brain damage and cell apoptosis.

Glucose metabolism-related protein 1 (GMRP1), also known as BTBD10, has been reported to inhibit apoptosis of neuronal and islet beta cells via the Akt pathway. The present study attempted to investigate whether GMRP1 and its mediated Akt pathway were involved in brain injury of rats after intracerebral hemorrhage (ICH). Rat models of ICH had been established successfully. Western blotting was used to investigate the levels of GMRP1 protein in the caudate nuclei tissues of the hemorrhagic and contralateral sides at 6 h, day 1, day 3, day 5, and day 7 after ICH. Phosphorylations of Akt was determined in caudate nuclei mentioned above. TUNEL assay was used to measure the cell apoptosis. GMRP1 protein levels, as well as phosphorylations of Akt, significantly decreased in caudate nuclei of the hemorrhagic side, compared with those of the contralateral side on day 1 and day 3 after ICH. Enhanced cell apoptosis was observed on the hemorrhagic side using TUNEL assay. We presented here evidence that a decreased GMRP1-mediated Akt pathway contributed to cell apoptosis on the hemorrhagic side, suggesting that GMRP1 plays an important role in brain damage after ICH.

Alteration of intracellular calcium and its modulator SLC24A6 after experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) can lead to tragic disability and mortality. Accumulating evidence has shown that sodium calcium exchanger (NCX) may contribute to the secondary injury of a stroke. Recently, a novel member of NCX, SLC24A6, was discovered with knowledge of its abundant distribution in brain. In the present study, we examined the time course of expression of SLC24A6 and its mediated intracellular calcium concentration ([Ca(2+)]i) to investigate its potential roles in brain damage after ICH. An ICH model was established as previously reported. Real-time PCR and Western blotting were used to test the mRNA and protein levels of SLC24A6 on the hemorrhagic side and on the contralateral side caudate nucleus tissues at 6 h, and on days 1, 3, 5, and 7 after ICH. Immunohistochemistry was used to analyze the morphological changes. Fura-2/AM loaded, dual wavelength spectrophotofluorometry was used to test [Ca(2+)]i. The data presented a remarkable decrease in SLC24A6 early after ICH, along with a comparable increase in [Ca(2+)]i. Our results indicated that SLC24A6 presents specific and remarkable alterations in both mRNA and protein levels after ICH. Decreases in SLC24A6 level were correlated with [Ca(2+)]i elevation. These data suggest that SLC24A6-mediated calcium overload plays an important role in brain damage after ICH.