Radiotherapy and surgery remain effective treatment options for retroperitoneal MPNST: a retrospective study based on SEER database.

Introduction: The proportion of retroperitoneal malignant peripheral nerve sheath tumours (RMPNST) in retroperitoneal tumors is less than 5%, but the mortality rate is very high. However, there is no relevant research focused on RMPNST only. Methods: We retrospectively analyzed data from the SEER database of patients with primary RMPNST from 2000 to 2019, by leveraging the advantages of the Seer database, we can explore the prognosis of such rare diseases. Kaplan-Meier method was used to construct the survival curve, and cox regression model was used to analyze the factors affecting the prognosis of patients. In addition, a model was developed to distinguish high-risk and low-risk patients. Results: This study included a total of 52 patients, with a median survival time of 39 months (95% CI 12.740-65.260) and a 5-year survival rate of 44.2% (95% CI 0.299-0.565). Radiotherapy (p = 0.004, OR: 1.475, 95% CI 0.718-3.033), metastasis disease (p = 0.002, OR: 5.596, 95% CI 2.449-47.079) and surgery (p = 0.003, OR: 5.003, 95% CI 0.011-0.409) were associated with overall survival (OS). The 5-year distant metastasis rate was 36% (95% CI 0.221-0.499). We used the above risk factors to separate patients into high and low groups and evaluate the results through the receiver operating characteristic (ROC) curve. This model is beneficial for guiding the selection of treatment strategies. Conclusion: The majority of RMPNST patients have a good prognosis after surgery, and the establishment of high-low group is helpful for clinical decision-making.

Revealing the "Yin-Jing" mystery veil of Platycodon grandiflorum by potentiating therapeutic effects and lung-oriented guidance property.

ETHNIC PHARMACOLOGICAL RELEVANCE: "Yin-Jing" medicine (YJM) has been widely used by both ancient and modern Chinese medicine practitioners during long-term clinical practice. However, it remains unclear how to best guide other medicines to the targeted organs in a traditional Chinese medicine (TCM) prescription. Here, in an attempt to explain the scientific connotation of the YJM property (YJMP) attributed to a basic TCM theory, Platycodon grandiflorum (PG) was chosen as a case study to reveal the mystery of YJMP theory. AIM OF THE STUDY: The main purpose of this study is to employ modern chemical and molecular biology methods to confirm the "Yin-Jing" effect of PG, and further clarify its material basis and related possible mechanism. MATERIALS AND METHODS: The ammonia-induced lung injury rat model was utilized to determine the optimal dosage of traditional prescription Hui Yan Zhu Yu decoction (HYZYD) using Wright Giemsa staining, HE staining, Masson staining, and TUNEL analysis. With the same way, PG was confirmed to have potentiating therapeutic effect (PTE) by comparison with HYZYD and [HYZYD-PG]. TMT proteomics was used to reveal the "Yin-Jing" mechanism of action. Western blot assay (WB) was employed for verification of differentially expressed proteins. Additionally, four non-crossing fragmentations (Fr. A-D) were characterized by RPLC/SEC-ELSD and HILIC-ESI--Q-OT-IT-MS techniques. The PTE and guidance property assays were utilized to evaluate "Yin-Jing" functions by a compatible combination of hydroxysafflor yellow A (HYA) using qPCR, FCM, WB, HPLC, high content cell imaging (HCI) and high-resolution live-cell imaging (HRLCI) techniques. RESULTS: The HYZYD-M (medium dose group) significantly improved the lung injury level in a pneumonia model of rats. PG enhanced the therapeutic effect of HYZYD ascribed to Yin-Jing PTE functions. TMT proteomics revealed a category of differentially expressed proteins ascribed to Golgi-ER between HYZYD and [HYZYD-PG]. Fr. C (i.e., saponins) and Fr. D (i.e., lipids) were determined as therapeutic fragmentations via the LPS-induced A549 cell injury model; however, Fr. B (fructooligosaccharides and small Mw fructans) had no therapeutic effect. Further compatibility PTE assays confirmed Fr. B significantly improved efficiency by a combination of HYA. The guidance assays showed Fr. B could significantly increase the uptake and distribution of HYA into lung cells and tissues. HCI assays showed that Fr. B increased uptake of HYA accompanied by significant activation of Golgi-ER. Unlike Fr. B, HRLCI showed that Fr. A, C and D were not only unobvious activations of Golgi-ER but also insignificant facilitation of colocalizations between HYA and Golgi-ER. CONCLUSIONS: Fr. B is believed to be a key YJMP material basis of PG attributed to Yin-Jing PTE with characteristic of lung-oriented guidance property, whereas another abound Fr. C was determined to have synergistic effects rather than Yin-Jing material basis.

Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma.

Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis (n = 10), metabolomic analysis (n = 51), and lipidomic analysis (n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.

Heme oxygenase­1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1.

Endotoxin-induced acute kidney injury (AKI) is commonly observed in clinical practice. Renal tubular epithelial cell (RTEC) pyroptosis is one of the main factors leading to the development of endotoxin-induced AKI. Mitochondrial dysfunction can lead to pyroptosis. However, the biological pathways involved in the potential lipopolysaccharide (LPS)-induced pyroptosis of RTECs, notably those associated with mitochondrial dysfunction, are poorly understood. Previous studies have demonstrated that heme oxygenase (HO)-1 confers cell protection via the induction of PTEN-induced putative kinase 1 (PINK1) expression through PTEN to regulate mitochondrial fusion/fission during endotoxin-induced AKI in vivo. Therefore, the present study investigated the role of HO-1/PINK1 in maintaining mitochondrial function and inhibiting the pyroptosis of RTECs exposed to LPS. Primary cultures of RTECs were obtained from wild-type (WT) and PINK1-knockout (PINK1KO) rats. An in vitro model of endotoxin-associated RTEC injury was established following treatment of the cells with LPS. The WT RTECs were divided into the control, LPS, Znpp + LPS and Hemin + LPS groups, and the PINK1KO RTECs were divided into the control, LPS and Hemin + LPS groups. RTECs were exposed to LPS for 6 h to assess cell viability, inflammation, pyroptosis and mitochondrial function. In the LPS-treated RTECs, the mRNA and protein expression levels of HO-1 and PINK1 were upregulated. Cell viability, adenosine triphosphate (ATP) levels and the mitochondrial oxygen consumption rate were decreased, whereas the inflammatory response, pyroptosis and mitochondrial reactive oxygen species (ROS) levels were increased. The cell inflammatory response and the induction of pyroptosis were inhibited, whereas the levels of mitochondrial ROS were decreased. In addition, the cell viability and ATP levels were increased in the WT RTECs following the upregulation of HO-1 expression. These effects were reversed by the downregulation of HO-1 expression. However, no statistically significant differences were noted between the LPS and the Hemin + LPS groups in the PINK1KO RTECs. Collectively, the findings of the present study indicate that HO-1 inhibits inflammation and regulates mitochondrial function by inhibiting the pyroptosis of LPS-exposed RTECs via PINK1.

[Effects of Vegetation Restoration on Soil Organic Carbon Sequestration and Aggregate Stability in Water-Eroded Environment: A Meta-analysis].

In order to clarify the differences in the effects of vegetation restoration strategies on soil carbon sequestration and aggregate stability under different water-eroded environments, we collected experimental data from 91 papers and evaluated the response of soil organic carbon (SOC) stock and aggregate stability to vegetation restoration based on Meta-analysis. The results showed the following:① compared with cropland or bare land, forestland/grassland restoration was beneficial to increase SOC stock and improve aggregate stability, but the dominant functions of the two were different. The effect of forestland restoration on carbon sequestration was stronger than that of grassland reforestation, and the effect of grassland restoration on aggregate stability was stronger than that of forestland restoration. ② Multi-factor Meta-analysis showed that the factors that significantly affected SOC were restoration year, soil clay content, vegetation coverage, mean annual precipitation (MAP), mean annual temperature (MAT), and soil depth. The positive effect of vegetation restoration on SOC stock increased with the increase in vegetation coverage rate. Grassland restoration had a more significant effect on SOC stock when soil clay content was 20%-32%, it was more likely to promote the carbon sequestration effect of grassland when MAP>800 mm or MAT<15℃, and there was no significant change in SOC stock under different restoration years. However, the effect of forestland restoration on SOC stock was more significant when soil clay content was>32%. Climate conditions had no limited effect on SOC stock in forestland, and there was a positive effect between SOC stock under forestland restoration and restoration years. ③ Vegetation restoration had stronger significant positive effects on mean weight diameter (MWD) and mean geometric diameter (GMD) when the clay content was 20%-32%, and MWD and GMD increased with the increase in vegetation coverage. ④SOC stock growth could explain 25% and 24% of the variation in the effect value of MWD and GMD, respectively. These results indicated that the formation of SOC was the result of multiple factors, and soil aggregate stability was limited only by vegetation coverage and soil clay content. The increase in SOC stock could promote the improvement of water stability MWD and GMD. These results can clarify the carbon sequestration effect of different vegetation restoration measures in water-eroded environments and provide theoretical reference for the restoration and reconstruction of degraded ecosystems.

Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress.

After spinal cord injury, the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase, and levels of both correlate with injury severity. Tau inhibition is considered effective therapy for many central nervous system diseases, including traumatic brain injury and Alzheimer's disease. However, whether it can play a role in the treatment of spinal cord injury remains unclear. In this study, the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression. We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin-6 and interleukin-1ß. It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype, and reduced the amount of reactive oxygen species in the acute phase. Furthermore, the survival of residual neural cells around the injury epicenter, and neuronal and axonal regeneration were also markedly enhanced, which promoted locomotor recovery in the model rats. Collectively, our findings support the conclusion that tau inhibition can attenuate neuroinflammation, alleviate oxidative stress, protect residual cells, facilitate neurogenesis, and improve the functional recovery after spinal cord injury, and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

Comparison of the supraglottic airway device BlockBusterTM and laryngeal mask airway Supreme in anaesthetised, paralyzed adult patients: a multicenter randomized controlled trial.

BACKGROUND: This multicenter prospective, randomized controlled clinical trial compared the clinical performance of supraglottic airway device (SAD) BlockBusterTM and laryngeal mask airway (LMA) Supreme for airway maintenance in anesthetized, paralyzed adult patients. METHODS: A total of 651 adult patients scheduled for elective surgery in 13 hospitals were randomly allocated into BlockBuster group (n = 351) or Supreme group (n = 300). The primary outcome was oropharyngeal leak pressure (OLP). Duration and ease of insertion, fiberscopic view of positioning, airway manipulations, and complications were also assessed. RESULTS: The OLP was significantly higher in BlockBuster group compared with Supreme group (29.9 ± 4.2 cmH2O vs 27.4 ± 4.3 cmH2O, p < 0.001). Success rate of insertion at the first attempt (90.2% vs 85.1%, p = 0.027), rate of optimal fiberscopic view (p = 0.002) and satisfactory positioning of SAD (p < 0.001) were significantly increased in BlockBuster group. CONCLUSIONS: Both SAD BlockBusterTM and LMA Supreme are safe, effective, and easy-to-use devices for airway maintenance in anesthetized, paralyzed adult patients, but the SAD BlockBusterTM is superior to LMA Supreme in terms of OLP, success rate at the first attempt, and fiber-optic view of positioning. TRIAL REGISTRATION: The trial is registered at www.chictr.org.cn (ChiCTR-ONC-16009105).

Critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases.

BACKGROUND: Major adverse cardiac events (MACE) in elderly patients with biliary diseases are the main cause of perioperative accidental death, but no widely recognized quantitative monitoring index of perioperative cardiac function so far. AIM: To investigate the critical values of monitoring indexes for perioperative MACE in elderly patients with biliary diseases. METHODS: The clinical data of 208 elderly patients with biliary diseases in our hospital from May 2016 to April 2021 were retrospectively analysed. According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group. RESULTS: In the MACE compared with the non-MACE group, postoperative complications, mortality, hospital stay, high sensitivity troponin-I (Hs-TnI), creatine kinase isoenzyme (CK-MB), myoglobin (MYO), B-type natriuretic peptide (BNP), and D-dimer (D-D) levels were significantly increased (P < 0.05). Multivariate logistic regression showed that postoperative BNP and D-D were independent risk factors for perioperative MACE, and their cut-off values in the receiver operating characteristic (ROC) curve were 382.65 pg/mL and 0.965 mg/L, respectively. CONCLUSION: The postoperative BNP and D-D were independent risk factors for perioperative MACE, with the critical values of 382.65 pg/mL and 0.965 mg/L respectively. Consequently, timely monitoring and effective maintenance of perioperative cardiac function stability are of great clinical significance to further improve the perioperative safety of elderly patients with biliary diseases.

Regenerative and Anti-Inflammatory Potential of Regularly Fed, Starved Cells and Extracellular Vesicles In Vivo.

BACKGROUND: Mesenchymal stem/stromal cells (MSC) have been employed successfully in immunotherapy and regenerative medicine, but their therapeutic potential is reduced considerably by the ischemic environment that exists after transplantation. The assumption that preconditioning MSC to promote quiescence may result in increased survival and regenerative potential upon transplantation is gaining popularity. METHODS: The purpose of this work was to evaluate the anti-inflammatory and regenerative effects of human bone marrow MSC (hBM-MSC) and their extracellular vesicles (EVs) grown and isolated in a serum-free medium, as compared to starved hBM-MSC (preconditioned) in streptozotocin-induced diabetic fractured male C57BL/6J mice. RESULTS: Blood samples taken four hours and five days after injection revealed that cells, whether starved or not, generated similar plasma levels of inflammatory-related cytokines but lower levels than animals treated with EVs. Nonetheless, starved cells prompted the highest production of IL-17, IL-6, IL-13, eotaxin and keratinocyte-derived chemokines and induced an earlier soft callus formation and mineralization of the fracture site compared to EVs and regularly fed cells five days after administration. CONCLUSIONS: Preconditioning may be crucial for refining and defining new criteria for future MSC therapies. Additionally, the elucidation of mechanisms underpinning an MSC's survival/adaptive processes may result in increased cell survival and enhanced therapeutic efficacy following transplantation.

Dual-Graph Attention Convolution Network for 3-D Point Cloud Classification.

Three-dimensional point cloud classification is fundamental but still challenging in 3-D vision. Existing graph-based deep learning methods fail to learn both low-level extrinsic and high-level intrinsic features together. These two levels of features are critical to improving classification accuracy. To this end, we propose a dual-graph attention convolution network (DGACN). The idea of DGACN is to use two types of graph attention convolution operations with a feedback graph feature fusion mechanism. Specifically, we exploit graph geometric attention convolution to capture low-level extrinsic features in 3-D space. Furthermore, we apply graph embedding attention convolution to learn multiscale low-level extrinsic and high-level intrinsic fused graph features together. Moreover, the points belonging to different parts in real-world 3-D point cloud objects are distinguished, which results in more robust performance for 3-D point cloud classification tasks than other competitive methods, in practice. Our extensive experimental results show that the proposed network achieves state-of-the-art performance on both the synthetic ModelNet40 and real-world ScanObjectNN datasets.

Systematic evaluation of COVID-19 related Internet health rumors during the breaking out period of COVID-19 in China.

Background: To adapt the scientific evaluation tool for the confusion evaluation of health rumors and to test this tool to the confusion evaluation of coronavirus disease 2019 (COVID-19)-related health rumors on Chinese online platforms during the outbreak period of COVID-19in China. Methods: The design of our study was systematic evaluation of COVID-19-related health rumors. Retrieved from 7 rumor-repellent platforms, rumors about COVID-19 were collected during the publication from December 1, 2019, to February 6, 2020, and their origins were traced. Researchers evaluated rumors using the confusion evaluation tool in 6 dimensions(creators, evidence selection, evidence evaluation, evidence application, backing and publication platform, conflict of interest). Items were scored using a seven-point Likert scale. The scores were converted into percentages, and the median of rumors from different sources was compared with rank-sum test. Results: Our research included 127 rumors. Scores were converted to percentages, median and interquartile range are used to describe the data. The median score: creators 25.00%(interquartile range, IQR, 16.67-37.50%), evidence selection 27.78% (IQR, 13.89-44.44%),evidence evaluation 33.33% (IQR, 25.00-45.83%), evidence application 36.11% (IQR, 22.22-47.22%), backing and publication platform 8.33% (IQR, 4.17-20.83%), conflict of interest75.00% (IQR, 50.00-83.33%). Almost 40% rumors came from WeChat and the rumors with the lowest scores were concentrated on the WeChat platform. The rumors about prevention methods have relatively lower scores. Conclusion: Most rumors included were not highly confusing for evaluators of this project.WeChat is the "worst-hit area" of COVID-19 related health rumors. More than half rumors focus on the description of prevention methods, which reflects the panic, anxiety and blind conformity of the public under public health emergencies.

Fabrication of a Polylactide-Glycolide/Poly-ε-Caprolactone/Dextran/Plastrum Testudinis Extract Composite Anti-Inflammation Nanofiber Membrane via Electrospinning for Annulus Fibrosus Regeneration.

Tissue engineering is a promising approach for the treatment of chronic lower back pain (LBP) caused by intervertebral disc degeneration (IDD) resulting from degeneration and inflammation of annulus fibrosus (AF) tissue. However, scaffold with an anti-inflammatory effect on AF cells has not been reported. In this study, we fabricated a polylactide-glycolide (PLGA)/poly-ε-caprolactone (PCL)Zdextran (DEX) composite membrane loaded with plastrum testudinis extract (PTE), a Traditional Chinese Medicine herbal extract, via electrospinning. The membranes were characterized by mechanical measurements and scanning electron microscopy (SEM). Using an in vitro inflammation model induced by interleukin (IL)-1ß, the cytocompatibility and anti-inflammatory effects of the composites were investigated by CCK-8 assay and flow cytometry. Potential regulatory mechanisms were examined by RT-qPCR and Western blotting. The results showed that the P10P8D2 (PLGA 10 g, PCL 8 g, DEX 2 g) composite nanofiber membrane exhibited the most uniform diameter distribution, best mechanical properties, a moderate degradation rate, and the best cytocompatibility characteristics. The optimal concentration of PTE was 120 µg/mL. Importantly, P10P8D2 combined with PTE exhibited anti-inflammatory and cell proliferation promotion effects. Moreover, the NF-κBB/NLRP3/IL-ß signaling pathway was inactivated. Our findings suggested that the nanofiber membrane composed of P10P8D2 and PTE has anti-inflammatory and pro-proliferation effects on AF cells. It may provide an effective strategy for AF tissue regeneration.

[Up-Regulation of Bax/BCL-2 Ratio by 2-Methoxyestradiol Induces Apoptosis in Lymphoma Raji Cells].

OBJECTIVE: To investigate the effect of 2-methoxyestradiol (2-ME2) to lymphoma Raji cells and its mechanism. METHODS: Different concentrations of 2-ME2 were used to treat lymphoma Raji cells. CCK8 method was used to detect the effect of 2-ME2 to proliferation of Raji cells. Flow cytometry FITC/PI double labeling method was used to detect early apoptosis of the cells. Western blotting was used to detect the effect of 2-ME2 to the expression of BCL-2, Bax, Caspase-3 and C-myc proteins in Raji cells. RESULTS: 2-ME2 significantly inhibited the proliferation of Raji cells. The inhibition rate increased with the increasing of drug concentration, and increased significantly with the prolongation of drug treatment time (r=0.9215). Flow cytometry FITC/PI double staining showed that the apoptotic rate of 2.5 µmol/L 2-ME2 treatment group was (33.79±1.63) %, while the apoptosis rate of the 48 h group was (51.90±2.72) %, and that of the control group was (7.08±0.36) %. After treated with 2.5 µmol/L 2-ME2 for 12 h, the expression of Bax protein was up-regulated, BCL-2 protein was down-regulated, caspase-3 protein expression was up-regulated, and C-myc protein expression was down-regulated, all of them showed a time-dependent relationship. CONCLUSION: 2-ME2 shows obvious inhibitory effect on lymphoma Raji cells in a dose- and time-dependent manner. Its mechanism of treatment on lymphoma Raji cells may be related to up-regulation of Bax/BCL-2 ratio and activation of Caspase-3 to induce apoptosis in cancer cells. Down-regulation of C-myc protein expression also participates in the apoptotic process.

[Study on time-toxicity relationship and mechanism of Gardeniae Fructus extract on hepatoxicity in rats based on proteomics].

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.

Analysis of clinical prognosis in patients with non-hepatic hyperammonemia.

ABSTRACT: The aim of this study was to evaluate the association of non-hepatic hyperammonemia (NHH) with the prognosis of critically ill patients with NHH.According to the serum ammonia level, the patients with NHH (n = 498) were retrieved by us. The risk factors of the mortality with NHH patients were investigated by conducting univariate and multivariate logistic regression analyses. A nomogram to predict the risk of hospital mortality was constructed. Receiver operating characteristic curve (ROC) analysis was conducted to compare nomogram (ammonia into a prognostic model, P1) with the simplified acute physiology II (SAPSII) and quick sequential organ failure assessment (qSOFA).Five independent factors for the mortality in patients with NHH were identified, including age, platelets, bun, hemoglobin, and ammonia. Models P1 using ammonia showed good prediction power. The AUROC of P1 (AUROC, 0.755 [95% CI, 0.713-0.796]) was higher than that of qSOFA (AUROC, 0.500 [95% CI, 0.449-0.551]), and SAPS II (AUROC, 0.703[95% CI, 0.658-0.748]).Ammonia was an independent prognostic predictor of mortality for NHH patients. We developed a nomogram that can predict hospital mortality with patients. Nomogram had superior discriminative power to qSOFA and SAPS II, indicating that the nomogram may have clinical utility.

Study on time-toxicity relationship and mechanism of Gardeniae Fructus extract on hepatoxicity in rats based on proteomics / 中国中药杂志

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.

Up-Regulation of Bax/BCL-2 Ratio by 2-Methoxyestradiol Induces Apoptosis in Lymphoma Raji Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of 2-methoxyestradiol (2-ME2) to lymphoma Raji cells and its mechanism.@*METHODS@#Different concentrations of 2-ME2 were used to treat lymphoma Raji cells. CCK8 method was used to detect the effect of 2-ME2 to proliferation of Raji cells. Flow cytometry FITC/PI double labeling method was used to detect early apoptosis of the cells. Western blotting was used to detect the effect of 2-ME2 to the expression of BCL-2, Bax, Caspase-3 and C-myc proteins in Raji cells.@*RESULTS@#2-ME2 significantly inhibited the proliferation of Raji cells. The inhibition rate increased with the increasing of drug concentration, and increased significantly with the prolongation of drug treatment time (r=0.9215). Flow cytometry FITC/PI double staining showed that the apoptotic rate of 2.5 μmol/L 2-ME2 treatment group was (33.79±1.63) %, while the apoptosis rate of the 48 h group was (51.90±2.72) %, and that of the control group was (7.08±0.36) %. After treated with 2.5 μmol/L 2-ME2 for 12 h, the expression of Bax protein was up-regulated, BCL-2 protein was down-regulated, caspase-3 protein expression was up-regulated, and C-myc protein expression was down-regulated, all of them showed a time-dependent relationship.@*CONCLUSION@#2-ME2 shows obvious inhibitory effect on lymphoma Raji cells in a dose- and time-dependent manner. Its mechanism of treatment on lymphoma Raji cells may be related to up-regulation of Bax/BCL-2 ratio and activation of Caspase-3 to induce apoptosis in cancer cells. Down-regulation of C-myc protein expression also participates in the apoptotic process.

Clinicopathological analysis of 719 pediatric and adolescents' ocular tumors and tumor-like lesions: a retrospective study from 2000 to 2018 in China.

AIM: To describe the clinicopathologic features and classification of pediatric and adolescent ocular tumors and tumor-like lesions. METHODS: A total of 719 cases of pathologically confirmed ocular tumors and tumor-like lesions in a pediatric population from two academic institutions over an 18-year period were retrospectively analyzed. The main outcome measures were the clinical and pathological features of the cases. RESULTS: Benign tumors accounted for 92.1% of all cases while malignant tumors accounted for 7.9%. The most common ocular benign tumors were (epi-)dermoid cysts (19.8%), nevi (15.2%), corneal dermoid tumors (9.8%), and calcified epitheliomas (8.8%). The most common ocular malignant tumors were retinoblastoma (80.8%), and rhabdomyosarcoma (3.9%). Eyelid and ocular surface tumors comprised 73.3% of benign tumors while intraocular and orbital cavity comprised 94.2% of malignant tumors. For tumor site, the upper eyelid was up to 1.79 times more than lower eyelid (P<0.05). Age at surgery and sex also had an association with different lesions (P=0.006, P=0.035, respectively). CONCLUSION: Most ocular tumors and tumor-like lesions in children and adolescents are benign. Pediatric ocular tumors are distinct from those in adults in terms of histological origin. (Epi-)dermoid cysts are the most common benign tumors while retinoblastomas the most common malignant tumors.

HO-1/PINK1 Regulated Mitochondrial Fusion/Fission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury.

BACKGROUND: Endotoxin-associated acute kidney injury (AKI), a disease characterized by marked oxidative stress and inflammation disease, is a major cause of mortality in critically ill patients. Mitochondrial fission and pyroptosis often occur in AKI. However, the underlying biological pathways involved in endotoxin AKI remain poorly understood, especially those related to mitochondrial dynamics equilibrium disregulation and pyroptosis. Previous studies suggest that heme oxygenase- (HO-) 1 confers cytoprotection against AKI during endotoxic shock, and PTEN-induced putative kinase 1 (PINK1) takes part in mitochondrial dysfunction. Thus, in this study, we examine the roles of HO-1/PINK1 in maintaining the dynamic process of mitochondrial fusion/fission to inhibit pyroptosis and mitigate acute kidney injury in rats exposed to endotoxin. METHODS: An endotoxin-associated AKI model induced by lipopolysaccharide (LPS) was used in our study. Wild-type (WT) rats and PINK1 knockout (PINK1KO) rats, respectively, were divided into four groups: the control, LPS, Znpp+LPS, and Hemin+LPS groups. Rats were sacrificed 6 h after intraperitoneal injecting LPS to assess renal function, oxidative stress, and inflammation by plasma. Mitochondrial dynamics, morphology, and pyroptosis were evaluated by histological examinations. RESULTS: In the rats with LPS-induced endotoxemia, the expression of HO-1 and PINK1 were upregulated at both mRNA and protein levels. These rats also exhibited inflammatory response, oxidative stress, mitochondrial fission, pyroptosis, and decreased renal function. After upregulating HO-1 in normal rats, pyroptosis was inhibited; mitochondrial fission and inflammatory response to oxidative stress were decreased; and the renal function was improved. The effects were reversed by adding Znpp (a type of HO-1 inhibitor). Finally, after PINK1 knockout, there is no statistical difference in the LPS-treated group and Hemin or Znpp pretreated group. CONCLUSIONS: HO-1 inhibits inflammation response and oxidative stress and regulates mitochondria fusion/fission to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.

Administration of Human Non-Diabetic Mesenchymal Stromal Cells to a Murine Model of Diabetic Fracture Repair: A Pilot Study.

Individuals living with type 1 diabetes mellitus may experience an increased risk of long bone fracture. These fractures are often slow to heal, resulting in delayed reunion or non-union. It is reasonable to theorize that the underlying cause of these diabetes-associated osteopathies is faulty repair dynamics as a result of compromised bone marrow progenitor cell function. Here it was hypothesized that the administration of non-diabetic, human adult bone marrow-derived mesenchymal stromal cells (MSCs) would enhance diabetic fracture healing. Human MSCs were locally introduced to femur fractures in streptozotocin-induced diabetic mice, and the quality of de novo bone was assessed eight weeks later. Biodistribution analysis demonstrated that the cells remained in situ for three days following administration. Bone bridging was evident in all animals. However, a large reparative callus was retained, indicating non-union. µCT analysis elucidated comparable callus dimensions, bone mineral density, bone volume/total volume, and volume of mature bone in all groups that received cells as compared to the saline-treated controls. Four-point bending evaluation of flexural strength, flexural modulus, and total energy to re-fracture did not indicate a statistically significant change as a result of cellular administration. An ex vivo lymphocytic proliferation recall assay indicated that the xenogeneic administration of human cells did not result in an immune response by the murine recipient. Due to this dataset, the administration of non-diabetic bone marrow-derived MSCs did not support fracture healing in this pilot study.