The tumorigenic effect of the high expression of ABRACL in glioma and its potential as a therapeutic target.

Gliomas are the most common malignant intracranial tumors, with no effective treatments. Better understanding and identification of novel targets are urgently warranted. Actin-binding Rho activating C-terminal like (ABRACL) has been reported as an oncogene in several cancer types. However, the potential roles of ABRACL in the tumorigenesis of malignant glioma remain unknown. We discovered that ABRACL is highly expressed in different sub-types of gliomas in both CGGA and TCGA databases, which was further validated in glioblastoma cell lines and normal human astrocyte lines. RT-qPCR, Western blotting and immunohistochemistry demonstrated that ABRACL expression in glioma tissues was upregulated along with the increasing WHO grades. Further survival analysis of glioma patients also revealed that the overall survival of patients in the ABRACL high expression level group were significantly shorter than those in the low expression level group. Knockdown of ABRACL inhibited the proliferation, cell migration, invasion and cytodynamics behaviors in glioma cell lines via activating STAT3 signaling, which also induced apoptosis and cell cycle arrest. Conversely, overexpressing ABRACL promoted cell renewing and migration, enabled more flexible cell deformation, supporting ABRACL being a bona fide oncogene. Intracranial orthotopic xenograft experiment further confirmed that ABRACL downregulation significantly suppressed glioma growth. These results have demonstrated that the tumorigenic effect of ABRACL is partly mediated by STAT3, whose expression also correlates with clinical prognosis. ABRACL facilitates glioma malignancy phenotype through regulating the cytoskeleton by activating STAT3 pathway, suggesting that it may represent a potential therapeutic target for glioblastoma.

Identifying and exploring the favorable factors that help to slow the progression of disease in patients with mild cervical spondylotic myelopathy.

To explore the favorable factors that help slow the progression of disease in patients with mild Cervical Spondylotic Myelopathy (CSM). A retrospective analysis was conducted, involving the enrollment of 115 CSM patients. The categorization of patients into two groups was based on the duration of symptoms, assessments using the mJOA scale and Health Transition (HT) scores: mild-slow group and severe-rapid group. We found that the patients in both groups had similar degrees of spinal cord compression, but mild-slow group were older and had smaller C2-C7 cobb angle (Flexion) (CL(F)), C2-C7 cobb angle (Range of motion) (CL(ROM)), Transverse area (TA), Normal-TA, Compressive spinal canal area (CSCA), Normal-Spinal canal area (Normal-SCA) and lower Spinal cord increased signal intensity (ISI) Grade than the severe-rapid group. A binary logistic regression analysis showed that CL(ROM) and Normal-TA are favorable factors to help slow the progression of disease patients with mild CSM. Through ROC curves, we found that when CL(ROM) < 39.1° and Normal-TA < 80.5mm2, the progression of disease in CSM patients may be slower. Meanwhile, we obtained a prediction formula by introducing joint prediction factor: L = CL(ROM) + 2.175 * Normal-TA. And found that when L < 213.0, the disease progression of patients may be slower which was superior to calculate CL(ROM) and Normal-TA separately.

SVIL promotes ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions through the TGF-ß/Smad pathway.

OBJECTIVE: Ovarian cancer is the malignant tumor with the highest mortality rate in gynecology. We aimed to identify novel genes that promote ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions. METHODS: We screened SVIL as a hypoxia-associated target in ovarian cancer and explored the related molecular mechanisms. We assessed the effects of SVIL on ovarian cancer progression and metastasis in clinical samples and cellular hypoxia models. Further, we investigated the relevant pathways of SVIL and confirmed the effects of SVIL on ovarian cancer progression by using nude mouse in situ tumor models. RESULTS: We found that SVIL was significantly highly expressed in the hypoxic environment of ovarian cancer, and SVIL expression correlated with patient prognosis.CCK8, Wound-healing assay, Transwell assay, Western Blot, and apoptosis assays revealed that knockdown of SVIL inhibited the activation of the TGFß1/smad2/3 pathway, which attenuated the progression and epithelial-mesenchymal transition(EMT) of ovarian cancer and alleviated cisplatin resistance by increasing cisplatin-induced apoptosis. Furthermore, in a nude mouse ovarian cancer in situ model, we found that the knockdown of SVIL significantly inhibited tumor growth and metastasis. CONCLUSION: SVIL highly expressed in the hypoxic microenvironment can increase ovarian cancer progression and cisplatin resistance by activating TGFß1/smad2/3 pathway. Our study demonstrated that SVIL may be a novel target for the treatment of ovarian cancer.

Effects of sitting position on ventilation distribution determined by electrical impedance tomography in ventilated ARDS patients.

OBJECTIVE: The study aimed to evaluate the improvements in pulmonary ventilation following a sitting position in ventilated ARDS patients using electrical impedance tomography. METHODOLOGY: A total of 17 patients with ARDS under mechanical ventilation participated in this study, including 8 with moderate ARDS and 9 with severe ARDS. Each patient was initially placed in the supine position (S1), transitioned to sitting position (SP) for 30 min, and then returned to the supine position (S2). Patients were monitored for each period, with parameters recorded. MAIN OUTCOME MEASURES: The primary outcome included the spatial distribution parameters of EIT, regional of interest (ROI), end-expiratory lung impedance (ΔEELI), and parameters of respiratory mechanics. RESULTS: Compared to S1, the SP significantly altered the distribution in ROI1 (11.29 ± 4.70 vs 14.88 ± 5.00 %, p = 0.003) and ROI2 (35.59 ± 8.99 vs 44.65 ± 6.97 %, p ＜ 0.001), showing reductions, while ROI3 (39.71 ± 11.49 vs 33.06 ± 6.34 %, p = 0.009), ROI4 (13.35 ± 8.76 vs 7.24 ± 5.23 %, p ＜ 0.001), along with peak inspiratory pressure (29.24 ± 3.96 vs 27.71 ± 4.00 cmH2O, p = 0.036), showed increases. ΔEELI decreased significantly ventrally (168.3 (40.33 - 189.5), p ＜ 0.0001) and increased significantly dorsally (461.7 (297.5 - 683.7), p ＜ 0.0001). The PaO2/FiO2 ratio saw significant improvement in S2 compared to S1 after 30 min in the seated position (108 (73 - 130) vs 96 (57 - 129) mmHg, p = 0.03). CONCLUSIONS: The sitting position is associated with enhanced compliance, improved oxygenation, and more homogenous ventilation in patients with ventilated ARDS compared to the supine position. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the impact of postural changes on patient pulmonary ventilation in order to standardize safe practices in critically ill patients. It may be helpful in the management among ventilated patients.

Bioactivity evaluation and active compounds identification of Symphoricarpos orbiculatus as potential botanical herbicide.

BACKGROUND: Evaluation of herbicidal activity and identification of active compounds are important bases for the development of new botanical herbicides. RESULTS: This study confirmed that Symphoricarpos orbiculatus has high herbicidal activities against mono-dicotyledonous weeds, including Echinochloa crusgalli, Digitaria sanguinalis, Amaranthus retroflexus and Portulaca oleracea. By bioassay-guided isolation, 12 compounds were isolated and identified from S. orbiculatus for the first time, including iridoids: naucledal (K1), loganin (K2), loganigenin (K3), loganin acid (K4), glucologanin (K5) and vogeloside (K6), as well as flavonoids: quercetine (K7), luteolin (K8), nobiletin (K9), astragalin (K10), isorhamnetin 3-d-glucoside (K11) and rutin (K12). Biological assays showed that iridoids are the main active ingredients of S. orbiculatus. The compounds of K5 and K6 could inhibit both the root (IC50 = 37.54 and 38.91 µg mL-1, respectively) and shoot (IC50 = 42.78 and 45.72 µg mL-1, respectively) of Portulaca oleracea, which have a weeding toxicity similar to that of the commercialized plant-based herbicide pelargonic acid. In addition, the results of pot culture assay showed that S. orbiculatus ethanol extracts had high fresh weight control effect against Digitaria sanguinalis and P. oleracea at the concentration of 40 g L-1. After 7 days, both the soil treatment and the stem and leaf spray method resulted in severe leaf necrosis and significant leaf etiolation. CONCLUSION: Symphoricarpos orbiculatus and its herbicidal active compounds have the potential to develop into botanical herbicides, and are first reported in the present study. © 2024 Society of Chemical Industry.

Edaravone combined with hyperbaric oxygen therapy in delayed encephalopathy after acute carbon monoxide poisoning: A meta-analysis.

BACKGROUND: The use of both edaravone (EDA) and hyperbaric oxygen therapy (HBOT) is increasingly prevalent in the treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). This meta-analysis aims to evaluate the efficacy of using EDA and HBOT in combination with HBOT alone in the treatment of DEACMP. METHODS: We searched and included all randomized controlled trials (RCTs) published before November 6, 2023, from 12 Chinese and English databases and clinical trial centers in China and the United States. The main outcome indicator was the total effective rate. The secondary outcome indicators included the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Hasegawa Dementia Scale (HDS), Fugl-Meyer Assessment (FMA), Superoxide Dismutase (SOD), and Malondialdehyde (MDA). Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (95 % CI). RESULTS: Thirty studies involving a combined total of 2075 participants were ultimately incorporated. It was observed that the combination of EDA with HBOT for the treatment of DEACMP demonstrated an improvement in the total effective rate (RR: 1.25; 95 % CI: 1.20-1.31; P < 0.01), MMSE (WMD: 3.67; 95 % CI: 2.59-4.76; P < 0.01), MoCA (WMD: 4.38; 95 % CI: 4.00-4.76; P < 0.01), BI (WMD: 10.94; 95 % CI: 5.23-16.66; P < 0.01), HDS (WMD: 6.80; 95 % CI: 4.05-9.55; P < 0.01), FMA (WMD: 8.91; 95 % CI: 7.22-10.60; P < 0.01), SOD (WMD: 18.45; 95 % CI: 16.93-19.98; P < 0.01); and a reduction in NIHSS (WMD: -4.12; 95 % CI: -4.93 to -3.30; P < 0.01) and MDA (WMD: -3.05; 95 % CI: -3.43 to -2.68; P < 0.01). CONCLUSION: Low-quality evidence suggests that for DEACMP, compared to using HBOT alone, the combined use of EDA and HBOT may be associated with better cognition and activity of daily living. In the future, conducting more meticulously designed multicenter and large-sample RCTs to substantiate our conclusions is essential.

The performance of a combination of heparin-binding protein with other biomarkers for sepsis diagnosis: an observational cohort study.

BACKGROUND: HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. METHODS: Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. RESULTS: A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p < 0.05) observed for all parameters. When compared to SOFA score and traditional markers of CRP, PCT, IL-6 and IL-8, the combined indexes of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB demonstrated significantly improved diagnostic performance for sepsis and septic shock (AUC 0.911 and 0.902 respectively, p < 0.001). CONCLUSIONS: The combined measurements of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB can augment the diagnostic capacity of HBP for sepsis, and offer reliable early supplementary indicators to traditional biomarkers for assessing disease severity in patients with infection.

The prognostic impact of tumor location in nonmuscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing Chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118 477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 ( P <0.0001); RFS of 2.21 ( P <0.0001); SEER cohort OS HR of 1.10 ( P =0.0001); DSS HR of 1.13 ( P =0.0183). Dome tumors displayed similar trends [Chinese NMIBC cohort OS HR of 7.91 ( P <0.0001); RFS HR of 2.12 ( P <0.0001); SEER OS HR of 1.05 ( P =0.0087); DSS HR of 1.14 ( P =0.0006)]. Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment ( P <0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage.

Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

[Application of Nice knot technique in wound closure of Gustilo type â ¢A and â ¢B open tibial fractures].

Objective: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. Methods: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. Results: The wound area was 21.0-180.0 cm 2 (mean, 57.82 cm 2) before operation, and it was 1.2-27.0 cm 2 (mean, 6.57 cm 2) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). Conclusion: Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.

SECTM1 promotes the development of glioblastoma and mesenchymal transition by regulating the TGFß1/Smad signaling pathway.

Objective: Secreted and transmembrane protein 1 (SECTM1) is a gene encoding a transmembrane protein. The role of SECTM1 in glioblastoma (GBM) is unclear. Here, we reported the abnormal expression of SECTM1 in GBM for the first time and studied the role and mechanism of SECTM1 in GBM. Methods: qRT-PCR, Western blotting and immunofluorescence were used to detect the expression of SECTM1 in gliomas of different grades and GBM cell lines. After the knockdown of SECTM1 expression in cell lines by shRNA, the effect of SECTM1 in GBM cell lines was verified by CCK-8, Transwell, EdU and wound healing experiments. We further investigated the effect and mechanism of SECTM1 on GBM in vitro and in vivo. The effect of SECTM1 on glioma growth was detected by subcutaneous tumor xenografts in nude mice in vivo. Results: The results showed that the knockdown of SECTM1 expression in cell lines significantly inhibited the proliferation, migration and invasion of GBM cells while inhibiting the progression of subcutaneous xenograft tumors in nude mice. However, the role and molecular mechanism of SECTM1 in GBM remain unclear. SECTM1 was found to promote GBM epithelial-mesenchymal transition (EMT) like processes. Bioinformatics analysis and Western blotting showed that SECTM1 regulates glioblastoma invasion and EMT-like processes mainly through the TGFß1/Smad signaling pathway. Conclusion: The low expression of SECTM1 has an inhibitory effect on GBM and is a potential target for GBM treatment. SECTM1 may also be a promising biomarker for the diagnosis and prognosis of GBM.

Hollow Cu2MoS4 nanoparticles loaded with immune checkpoint inhibitors reshape the tumor microenvironment to enhance immunotherapy for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to single-drug immunotherapy with PD-L1 (CD274) inhibitors. Here, we prepared mesoporous nanomaterials Cu2MoS4 (CMS)/PEG loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. In vitro experiments, CMS/PEG-B-P have a more substantial inhibitory effect on the expression of PD-L1 and CXCR4 as well as to promote the apoptosis of pancreatic cancer cells KPC and suppressed KPC cell proliferation were detected by flow cytometry, qPCR and Western blotting (WB). Promotes the release of the cytotoxic substance reactive oxygen species (ROS) and the production of the immunogenic cell death (ICD) marker calreticulin (CRT) in KPC cells. CMS/PEG-B-P was also detected to have a certain activating effect on mouse immune cells, dendritic cells (mDC) and macrophage RAW264.7. Subcutaneous tumorigenicity experiments in C57BL/6 mice verified that CMS/PEG-B-P had an inhibitory effect on the growth of tumors and remodeling of the tumor immune microenvironment, including infiltration of CD4+ and CD8+ T cells and polarization of macrophages, as well as reduction of immunosuppressive cells. Meanwhile, CMS/PEG-B-P was found to have different effects on the release of cytokines in the tumor immune microenvironment, including The levels of immunostimulatory cytokines INF-γ and IL-12 are increased and the levels of immunosuppressive cytokines IL-6, IL-10 and IFN-α are decreased. In conclusion, nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach. STATEMENT OF SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that has a low response to single-drug immunotherapy with PD-L1 (CD274) inhibitors. We preared PEG-modified mesoporous nanomaterials Cu2MoS4 (CMS) loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. Our study demonstrated that Nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach.

Prognostic value of serum ammonia in critical patients with non-hepatic disease: A prospective, observational, multicenter study.

Background and Objectives: Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU). Materials and Methods: This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia. Results: A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia (P < 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07-2.80, P = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, P < 0.001) remained the most predictive factor for patient prognosis by ROC analysis. Conclusion: Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.

Identification and validation of a novel necroptosis-related molecular signature to evaluate prognosis and immune features in breast cancer.

Necroptosis has been shown to play an important role in the development of tumors. However, the characteristics of the necroptosis-related subtypes and the associated immune cell infiltration in the tumor microenvironment (TME) of breast cancer (BRCA) remain unclear. In this study, we identified three clusters related to necroptosis using the expression patterns of necroptosis-relevant genes (NRGs), and found that these three clusters had different clinicopathological features, prognosis and immune cell infiltration in the TME. Cluster 2 was characterized by less infiltration of immune cells in the TME and was associated with a worse prognosis. Then, a necroptosis risk score (NRS) composed of 14 NRGs was constructed using the least absolute shrinkage and selection operator regression (LASSO) Cox regression method. Based on NRS, all BRCA patients in the TCGA datasets were classified into a low-risk group and a high-risk group. Patients in the low-risk group were characterized by longer overall survival (OS), lower mutation burden, and higher infiltration level of immune cells in the TME. Moreover, the NRS was significantly associated with chemotherapeutic drug sensitivity. Finally, the knockdown of VDAC1 reduced the proliferation and migration of BRCA cells, and promoted cell death induced by necroptosis inducer. This study identified a novel necroptosis-related subtype of BRCA, and a comprehensive analysis of NRGs in BRCA revealed its potential roles in prognosis, clinicopathological features, TME, chemotherapy, tumor proliferation, and tumor necroptosis. These results may improve our understanding of NRGs in BRCA and provide a reference for developing individualized therapeutic strategies.

[Percutaneous hollow screw internal fixation combined with cementoplasty in treatment of periacetabular metastasis].

Objective: To explore the percutaneous hollow screw internal fixation combined with cementoplasty in the treatment of periacetabular metastasis. Methods: A retrospective study was performed on 16 patients with periacetabular metastasis who were treated with percutaneous hollow screw internal fixation combined with cementoplasty between May 2020 and May 2021. There were 9 males and 7 females. The age ranged from 40 to 73 years, with an average of 53.6 years. The tumor involved around the acetabulum, and 6 cases were located on the left and 10 cases on the right. Operation time, frequency of fluoroscopy, bed rest time, and complications were recorded. Before operation, and at 1 weeks, 3 months after operation, the visual analogue scale (VAS) score was used to evaluate the pain degree, the short-form 36 health survey scale (SF-36) score was used to evaluate the quality of life. At 3 months after operation, the Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the functional recovery of patients. During follow-up, the loosening of internal fixator and bone cement leakage were observed by X-ray film. Results: All patients were performed operation successfully. The operation time ranged from 57 to 82 minutes, with an average of 70.4 minutes. The frequency of intraoperative fluoroscopy was 16-34 times, with an average of 23.1 times. After operation, 1 case of incision hematoma and 1 case of scrotal edema occurred. All patients felt the pain relieved after operation. The patients started walking at 1-3 days after operation, with an average of 1.4 days. All patients were followed up 6-12 months (mean 9.7 months). The VAS and SF-36 scores significantly improved after operation when compared with the preoperative scores, and the scores at 3 months after operation were significant better than those at 1 week after operation ( P<0.05). At 3 months after operation, the MSTS score ranged from 9 to 27, with an average of 19.8. Among them, 3 cases were excellent (18.75%), 8 cases were good (50%), 3 cases were fair (18.75%), and 2 cases were poor (12.5%). The excellent and good rate was 68.75%. And 11 patients returned to normal walking, 3 had mild claudication, and 2 had obvious claudication. Radiological examination showed that there were 2 cases of bone cement leakage after operation, and there was no internal fixator loosening or displacement. Conclusion: Percutaneous hollow screw internal fixation combined with cementoplasty can effectively relieve pain and improve the quality of life of patients with periacetabular metastasis.

Promotion of Egg Production Rate and Quality Using Limosilactobacillus oris BSLO 1801, a Potential Probiotic Screened from Feces of Laying Hens with Higher Egg Productive Performance.

In this experiment, laying hens were divided into a high productive group (group H) and a low productive group (group L). The purpose of this experiment was to screen and isolate a potential probiotic associated with the laying rate from group H by comparing the results via 16S rDNA high-throughput sequencing. The high-throughput sequencing analysis results showed that there were some differences in the composition of the gut microbiome between groups H and L on the Phylum and Genus levels. Through isolation and identification, we screened 16 lactobacilli strains. Among the 16 strains, S5 showed good acid tolerance, bile salt tolerance, and cholesterol degradation. Therefore, we chose strain S5 (identified as Limosilactobacillus oris, named Limosilactobacillus oris BSLO 1801) as a potential probiotic to promote the productivity of ordinary laying hens. During the animal experiment, 288 Hy-line white hens (30 weeks old) were divided into four groups, with six replications (n = 12) per group. The control group received the basic diet, and the treatment groups received the same basic diet supplemented with 107 CFU/kg, 108 CFU/kg, and 109 CFU/kg of BSLO 1801. The laying hens were acclimated to the environment for 1 week before the initiation of the experiment. Dietary supplementation with 107 CFU/kg and 109 CFU/kg of BSLO 1801 increased the laying rate significantly, and the potential probiotic improved the egg weight in all treatment groups. Additionally, the cholesterol content of the yolk dropped significantly in the 109 CFU/kg group, and the weight of egg yolk was significantly increased in all treatment groups. However, no significant differences in eggshell strength, eggshell thickness, protein height, and Haugh unit were observed among the four groups. These results revealed that lactobacilli spp. are important bacteria of the intestinal microbiome in highly productive laying hens, and BSLO 1801 was isolated as a potential probiotic. Through these animal experiments, we also found that adding BSLO 1801 to the basic diet of laying hens could effectively improve the laying rate, average egg weight, and yolk weight and reduce the cholesterol content in egg yolk.

Three-dimensional High-definition Exoscope in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Retrospective Cohort Study.

OBJECTIVES: The operative microscope (OM) has revolutionized the field of modern spine surgery, however, it remains limited by several drawbacks. Recently, the exoscope (EX) system has been designed to assistant spine surgery. It provides a three-dimensional (3D) high-definition (HD) operative experience and becomes an alternative to the OM. The aim of the study was to evaluate the clinical outcomes, advantages and limitations of EX-assisted minimally invasive transforaminal lumbar interbody fusion (EMIS-TLIF) and OM-assisted MIS-TLIF (OMIS-TLIF). METHODS: The clinical outcomes were assessed in 47 patients with lumbar degenerative diseases (LDD) who underwent MIS-TLIF assisted with the OM or EX between January 2019 and September 2020. A total of 22 were treated with EMIS-TLIF, and 25 received OMIS-TLIF. Perioperative parameters (including sex, age, number of fusion levels and body mass index), perioperative parameters (operation time, intraoperative blood loss, postoperative drainage, postoperative hospitalization stay, and duration of follow-up), visual analogue scale (VAS) of back pain, VAS of leg pain, Oswestry disability index (ODI) scores and clinical outcomes were assessed and compared. Image quality, handling of equipment, ergonomics, 3D glasses and educational usefulness were scored according to a questionnaire. RESULTS: Operation time in the OMIS-TLIF group (121.92 ± 16.92 min) was significantly increased compared with that in the EMIS-TLIF group (111.00 ± 19.87 min) (P < 0.05). The VAS of the back pain and ODI scores in the EMIS-TLIF group were significantly lower compared with the OMIS-TLIF group at 1 week postoperatively (P < 0.05). The good-excellent outcomes rate was 90.91% in the EMIS-TLIF group and 88.00% in the OMIS-TLIF group, and there was no significant difference. A total of 44 visits completed the questionnaire. The results of the questionnaire showed that the EX has exhibited advantages regarding handing of equipment, ergonomics and educational usefulness, and comparable image quality as compared with the OM, however, operating surgeons complained uncomfortable sensation when wearing 3D glasses. CONCLUSIONS: The EMIS-TLIF was a safe and effective procedure in the management of LDD as compared with the OMIS-LIF. Meanwhile, EMIS-TLIF might resulted in a short operation time.

Efficiently targeted therapy of glioblastoma xenograft via multifunctional biomimetic nanodrugs.

BACKGROUND: Glioblastoma multiforme (GBM) is a fatal malignant primary brain tumor in adults. The therapeutic efficacy of chemotherapeutic drugs is limited due to the blood-brain barrier (BBB), poor drug targeting, and short biological half-lives. Multifunctional biomimetic nanodrugs have great potential to overcome these limitations of chemotherapeutic drugs. METHODS: We synthesized and characterized a biomimetic nanodrug CMS/PEG-DOX-M. The CMS/PEG-DOX-M effectively and rapidly released DOX in U87 MG cells. Cell proliferation and apoptosis assays were examined by the MTT and TUNEL assays. The penetration of nanodrugs through the BBB and anti-tumor efficacy were investigated in the orthotopic glioblastoma xenograft models. RESULTS: We showed that CMS/PEG-DOX-M inhibited cell proliferation of U87 MG cells and effectively induced cell apoptosis of U87 MG cells. Intracranial antitumor experiments showed that free DOX hardly penetrated the BBB, but CMS/PEG-DOX-M effectively reached the orthotopic intracranial tumor through the BBB and significantly inhibited tumor growth. Immunofluorescence staining of orthotopic tumor tissue sections confirmed that nanodrugs promoted apoptosis of tumor cells. This study developed a multimodal nanodrug treatment system with the enhanced abilities of tumor-targeting, BBB penetration, and cancer-specific accumulation of chemotherapeutic drugs by combining chemotherapy and photothermal therapy. It can be used as a flexible and effective GBM treatment system and it may also be used for the treatment of other central nervous systems (CNS) tumors and extracranial tumors.