Electroencephalography-based biological and functional characteristics of spinal cord injury patients with neuropathic pain and numbness.

Objectives: To identify potential treatment targets for spinal cord injury (SCI)-related neuropathic pain (NP) by analysing the differences in electroencephalogram (EEG) and brain network connections among SCI patients with NP or numbness. Participants and methods: The EEG signals during rest, as well as left- and right-hand and feet motor imagination (MI), were recorded. The power spectral density (PSD) of the θ (4-8 Hz), α (8-12 Hz), and ß (13-30 Hz) bands was calculated by applying Continuous Wavelet Transform (CWT) and Modified S-transform (MST) to the data. We used 21 electrodes as network nodes and performed statistical measurements of the phase synchronisation between two brain regions using a phase-locking value, which captures nonlinear phase synchronisation. Results: The specificity of the MST algorithm was higher than that of the CWT. Widespread non-lateralised event-related synchronization was observed in both groups during the left- and right-hand MI. The PWP (patients with pain) group had lower θ and α bands PSD values in multiple channels of regions including the frontal, premotor, motor, and temporal regions compared with the PWN (patients with numbness) group (all p < 0.05), but higher ß band PSD values in multiple channels of regions including the frontal, premotor, motor, and parietal region compared with the PWN group (all p < 0.05). During left-hand and feet MI, in the lower frequency bands (θ and α bands), the brain network connections of the PWP group were significantly weaker than the PWN group except for the frontal region. Conversely, in the higher frequency bands (ß band), the brain network connections of the PWP group were significantly stronger in all regions than the PWN group. Conclusion: The differences in the power of EEG and network connectivity in the frontal, premotor, motor, and temporal regions are potential biological and functional characteristics that can be used to distinguish NP from numbness. The differences in brain network connections between the two groups suggest that the distinct mechanisms for pain and numbness.

Purification of Photorhabdus Virulence Cassette (PVC) Protein Complexes from Escherichia coli for Artificial Translocation of Heterologous Cargo Proteins.

Contractile injection systems (CISs), one of the most important bacterial secretion systems that transport substrates across the membrane, are a collection of diverse but evolutionarily related macromolecular devices. Numerous effector proteins can be loaded and injected by this secretion complex to their specific destinations. One group of CISs called extracellular CIS (eCIS) has been proposed as secretory molecules that can be released from the bacterial cytoplasm and attack neighboring target cells from the extracellular environment. This makes them a potential delivery vector for the transportation of various cargos without the inclusion of bacterial cells, which might elicit certain immunological responses from hosts. We have demonstrated that the Photorhabdus virulence cassette (PVC), which is a typical eCIS, could be applied as an ideal vector for the translocation of proteinaceous cargos with different physical or chemical properties. Here, we describe the in-depth purification protocol of this mega complex from Escherichia coli. The protocol provided is a simpler, faster, and more productive way of generating the eCIS complexes than available methodologies reported previously, which can facilitate the subsequent applications of these nanodevices and other eCIS in different backgrounds.

Asiatic Acid Alleviates Lipopolysaccharide-Induced Acute Myocardial Injury by Promoting Mitophagy and Regulating Mitochondrial Dynamics in Broilers.

Acute myocardial injury (AMI) induced by lipopolysaccharide (LPS) can cause cardiovascular dysfunction and lead to death in poultry. Traditional antibiotic therapy has been found to have many limitations and negative effects. Asiatic acid (AA) is a naturally occurring pentacyclic triterpenoid that is extracted from Centella asiatica and has anti-inflammatory, antioxidant, and anticancer pharmacological properties. Previously, we studied the effect of AA on LPS-induced liver and kidney injury; however, the impact of AA on LPS-induced AMI remained unclear. Sixty 1-day-old broilers were randomly divided into control group, LPS group, LPS + AA 15 mg/kg group, LPS + AA 30 mg/kg group, LPS + AA 60 mg/kg group, and control + AA 60 mg/kg group. The histopathology of cardiac tissues was detected by hematoxylin and eosin (H&E) staining. The mRNA and protein expressions related to mitochondrial dynamics and mitophagy were detected by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemistry. Disorganized myocardial cells and fractured myocardial fibers were found in the LPS group, and obvious red-blood-cell filling can be seen in the gaps between the myocardial fibers in the low-dose AA group. Nevertheless, the medium and high dose of AA obviously attenuated these changes. Our results showed that AA significantly restored the mRNA and protein expressions related to mitochondrial dynamic through further promoting mitophagy. This study revealed the effect of AA on LPS-induced AMI in broilers. Mechanically, AA regulated mitochondrial dynamic homeostasis and further promoted mitophagy. These novel findings indicate that AA may be a potential drug for LPS-induced AMI in broilers.

El ácido asiático como mitigante de las lesiones miocárdicas agudas inducidas por lipopolisacáridos al promover la mitofagia y regular la dinámica mitocondrial en pollos de engorde. La lesión miocárdica aguda (con siglas en inglés IAM) inducida por lipopolisacáridos (LPS) puede causar disfunción cardiovascular y provocar la muerte en las aves comerciales. Se ha descubierto que la terapia tradicional con antibióticos tiene muchas limitaciones y efectos negativos. El ácido asiático (AA) es un triterpenoide pentacíclico natural que se extrae de la planta Centella asiática y que tiene propiedades farmacológicas antiinflamatorias, antioxidantes y anticancerígenas. Anteriormente, se estudió el efecto del ácido asiático sobre la lesión hepática y renal inducida por lipopolisacáridos; sin embargo, el impacto del ácido asiático en las lesiones miocárdicas agudas inducidas por lipopolisacáridos continua sin estar completamente determinada. Sesenta pollos de engorde de un día de edad se dividieron aleatoriamente en los siguientes grupos experimentales: grupo control, grupo que recibió LPS solamente, grupo LPS + ácido asiático 15 mg/kg, grupo LPS + ácido asiático 30 mg/kg, grupo LPS + ácido asiático 60 mg/kg y control + ácido asiático 60 mg./kg grupo. La histopatología de los tejidos cardíacos se detectó mediante tinción con hematoxilina y eosina (H&E). Las expresiones de ARN mensajero y proteínas relacionadas con la dinámica mitocondrial y la mitofagia se detectaron mediante PCR cuantitativa en tiempo real, inmunotransferencia Western, inmunofluorescencia e inmunohistoquímica. Se encontraron células miocárdicas desorganizadas y fibras miocárdicas fracturadas en el grupo que recibió lipopolisacáridos, y se puede observar un evidente acúmulo de glóbulos rojos en los espacios entre las fibras miocárdicas en el grupo de dosis bajas de ácido asiático. Sin embargo, las dosis medias y altas de ácido asiático obviamente atenuaron estos cambios. Nuestros resultados mostraron que el ácido asiático restableció significativamente las expresiones de ARN mensajero y proteínas relacionadas con la dinámica mitocondrial mediante la promoción adicional de la mitofagia. Este estudio reveló el efecto del ácido asiático sobre las lesiones miocárdicas agudas inducidas por lipopolisacáridos en pollos de engorde. Basicamente, el ácido asiático reguló la homeostasis dinámica mitocondrial y promovió aún más la mitofagia. Estos nuevos hallazgos indican que el ácido asiático puede ser un fármaco potencial para mitigar lesiones miocárdicas agudas inducidas por lipopolisacáridos en pollos de engorde.

Polystyrene nanoplastics and cadmium co-exposure aggravated cardiomyocyte damage in mice by regulating PANoptosis pathway.

Micro/nanoplastics (M/NPs) are the novel contaminants ubiquitous in the environment. Cadmium (Cd), a kind of heavy metal pollutant widely distributed, could potentially co-exist with PS-NPs in the environment. However, their combined effects on cardiomyocyte and its molecular mechanism in mammals remained ambiguous. Here, we examined whether PANoptosis, an emerging and complicated kind of programmed cell death, was involved in PS-NPs and Cd co-exposure-elicited cardiac injury. In this study, 60 male mice were orally subjected to environmentally relevant concentrations of PS-NPs (1 mg/kg) and/or CdCl2 (1.5 mg/kg) for 35 days. As we speculated, PS-NPs and Cd co-exposure affected the expression of pyroptosis(Caspase-1, Cleaved-Caspase-1, GSDMD, N-GSDMD, AIM2, Pyrin, NLRP3, IL-18, IL-1ß)-, apoptosis(Caspase-3, Cleaved-Caspase-3, Caspase-8, Cleaved-Caspase-8, Caspase-7, BAX)- and necroptosis (t-RIPK3, p-RIPK3, t-RIPK1, p-RIPK1, t-MLKL, p-MLKL, ZBP1)-related genes and protein, resulting in growth restriction and damaged myocardial microstructure in mice. Notably, the combined effects on Cd and PS-NPs even predominantly aggravated the toxic damage. Intriguingly, we fortuitously discovered PS-NPs and/or Cd exposure facilitated linear ubiquitination of certain proteins in mice myocardium. In summation, this study shed light toward the effects of Cd and PS-NPs on cardiotoxicity, advanced the understanding of myocardial PANoptosis and provided a scientific foundation for further exploration of the combined toxicological effects of PS-NPs and heavy metals.

High-Quality Assembly and Analysis of the Complete Mitogenomes of German Chamomile (Matricaria recutita) and Roman Chamomile (Chamaemelum nobile).

German chamomile (Matricaria chamomilla L.) and Roman chamomile (Chamaemelum nobile) are the two well-known chamomile species from the Asteraceae family. Owing to their essential oils and higher medicinal value, these have been cultivated widely across Europe, Northwest Asia, North America, and Africa. Regarding medicinal applications, German chamomile is the most commonly utilized variety and is frequently recognized as the "star among medicinal species". The insufficient availability of genomic resources may negatively impact the progression of chamomile industrialization. Chamomile's mitochondrial genome is lacking in extensive empirical research. In this study, we achieved the successful sequencing and assembly of the complete mitochondrial genome of M. chamomilla and C. nobile for the first time. An analysis was conducted on codon usage, sequence repeats within the mitochondrial genome of M. chamomilla and C. nobile. The phylogenetic analysis revealed a consistent positioning of M. chamomilla and C. nobile branches within both mitochondrial and plastid-sequence-based phylogenetic trees. Furthermore, the phylogenetic analysis also showed a close relationship between M. chamomilla and C. nobile within the clade comprising species from the Asteraceae family. The results of our analyses provide valuable resources for evolutionary research and molecular barcoding in chamomile.

Protein-Templated Ugi Reactions versus In-Situ Ligation Screening: Two Roads to the Identification of SARS-CoV-2 Main Protease Inhibitors.

Protein-templated fragment ligation was established as a method for the rapid identification of high affinity ligands, and multicomponent reactions (MCR) such as the Ugi four-component reaction (Ugi 4CR) have been efficient in the synthesis of drug candidates. Thus, the combination of both strategies should provide a powerful approach to drug discovery. Here, we investigate protein-templated Ugi 4CR quantitatively using a fluorescence-based enzyme assay, HPLC-QTOF mass spectrometry (MS), and native protein MS with SARS-CoV-2 main protease as template. Ugi reactions were analyzed in aqueous buffer at varying pH and fragment concentration. Potent inhibitors of the protease were formed in presence of the protein via Ugi 4CR together with Ugi three-component reaction (Ugi 3CR) products. Binding of inhibitors to the protease was confirmed by native MS and resulted in the dimerization of the protein target. Formation of Ugi products was, however, more efficient in the non-templated reaction, apparently due to interactions of the protein with the isocyanide and imine fragments. Consequently, in-situ ligation screening of Ugi 4CR products was identified as a superior approach to the discovery of SARS-CoV-2 protease inhibitors.

Tert-butylhydroquinone attenuates LPS-induced pyroptosis of IPEC-J2 cells via downregulating HMGB1/TLR4/NF-κB axis.

Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert-butylhydroquinone (TBHQ) is a food additive that has the effect of anti-inflammation and anti-oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC-J2) cells. Quantitative real-time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high-mobility group box 1/toll-like receptor 4/nuclear factor kappa-B (HMGB1/TLR4/NF-κB) axis. Localisation and expression of NOD-like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P-NF-κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 µM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose-dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC-J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens-1, occludin and claudin-1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF-κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF-κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P-NF-κB in LPS-induced injury of IPEC-J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS-induced pyroptosis in IPEC-J2 cells through downregulation of the HMGB1/TLR4/NF-κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.

N-acetylcysteine combined with insulin attenuates myocardial injury in canines with type 1 diabetes mellitus by modulating TNF-α-mediated apoptotic pathways and affecting linear ubiquitination.

The exact pathogenesis of type 1 diabetes mellitus (DM) is still unclear. Numerous organs, including the heart, will suffer damage and malfunction as a result of long-term hyperglycemia. Currently, insulin therapy alone is still not the best treatment for type 1 DM. In order to properly treat and manage patients with type 1 DM, it is vital to seek a combination that includes both insulin and additional medications. This study aims to explore the therapeutic effect and mechanism of N-acetylcysteine (NAC) combined with insulin on type 1 DM. By giving beagle canines injections of streptozotocin (STZ) and alloxan (ALX) (20 mg/kg each), a model of type 1 DM was created. The results showed that this combination could effectively control blood sugar level, improve heart function, avoid the damage of mitochondria and myocardial cells, and prevent the excessive apoptosis of myocardial cells. Importantly, the combination can activate nuclear factor kappa-B (NF-κB) by promoting linear ubiquitination of receptor-interacting protein kinase 1 (RIPK1) and NF-κB-essential modulator (NEMO) and inhibitor of NF-κB (IκB) phosphorylation. The combination can increase the transcription and linear ubiquitination of Cellular FLICE (FADD-like IL-1ß-converting enzyme) -inhibitory protein (c-FLIP), diminish the production of cleaved-caspase-8 p18 and cleaved-caspase-3 to reduce apoptosis. This study confirmed that NAC combined with insulin can promote the linear ubiquitination of RIPK1, NEMO and c-FLIP and regulate the apoptosis pathway mediated by TNF-α to attenuate the myocardial injury caused by type 1 DM. Meanwhile, the research served as a resource when choosing a clinical strategy for DM cardiac complications.

Co-exposure to environmentally relevant concentrations of cadmium and polystyrene nanoplastics induced oxidative stress, ferroptosis and excessive mitophagy in mice kidney.

Nanoplastics (NPs) are defined as a group of emerging pollutants. However, the adverse effect of NPs and/or heavy metals on mammals is still largely unclear. Therefore, we performed a 35-day chronic toxicity experiment with mice to observe the impacts of exposure to Cadmium (Cd) and/or polystyrene nanoplastics (PSNPs). This study revealed that combined exposure to Cd and PSNPs added to the mice's growth toxicity and kidney damage. Moreover, Cd and PSNPs co-exposure obviously increased the MDA level and expressions of 4-HNE and 8-OHDG while decreasing the activity of antioxidase in kidneys via inhibiting the Nrf2 pathway and its downstream genes and proteins expression. More importantly, the results suggested for the first time that Cd and PSNPs co-exposure synergistically increased iron concentration in kidneys, and induced ferroptosis through regulating expression levels of SLC7A11, GPX4, PTGS2, HMGB1, FTH1 and FTL. Simultaneously, Cd and PSNPs co-exposure further increased the expression levels of Pink, Parkin, ATG5, Beclin1, and LC3 while significantly reducing the P62 expression level. In brief, this study found that combined exposure to Cd and PSNPs synergistically caused oxidative stress, ferroptosis and excessive mitophagy ultimately aggravating kidney damage in mice, which provided new insight into the combined toxic effect between heavy metals and PSNPs on mammals.

Asiatic acid alleviates LPS-induced acute kidney injury in broilers by inhibiting oxidative stress and ferroptosis via activation of the Nrf2 pathway.

Asiatic acid (AA), a triterpenoid compound isolated from Centella asiatica, has anti-inflammatory, antioxidant and anticancer biological characteristics. To explore the effect of AA on LPS-induced acute kidney injury (AKI) in broilers, a total of 60 one-day-old broilers were randomly divided into 6 groups, including the normal group, AKI model group, AKI + AA 15 mg/kg group, AKI + AA 30 mg/kg group, AKI + AA 60 mg/kg group and normal + AA 60 mg/kg group. Hematoxylin-eosin staining was used to observe the histopathology in kidney tissue, and the mRNA and protein expressions related to oxidative stress and ferroptosis were tested by qPCR and western blotting respectively. AA mitigated vacuolar degeneration and enlarged glomerular space caused by LPS in kidney tissue. Additionally, AA significantly increased the mRNA levels of Nrf2, HO-1, NQO1, GCLC, GCLM, GPX4, SLC7A11 and FTH1, and decreased the mRNA levels of Keap1 and PTGS2 in LPS-induced AKI. Likewise, AA significantly upregulated the protein expressions of Nrf2, HO-1, NQO1, GPX4, SLC7A11 and FTH1, and downregulated the protein expressions of Keap1 and PTGS2 in LPS-induced AKI. These results suggested that AA alleviated LPS-induced AKI by inhibiting oxidative stress and ferroptosis through targeting regulation of the Nrf2 pathway in broilers.

Differences According to Sex in the Relationship between Social Participation and Well-Being: A Network Analysis.

This study aimed to explore the effects of different types of social participation on the components of well-being, as well as the differences according to sex in the relationship between social participation and well-being. This was a cross-sectional community study. Well-being was measured using the positive emotion, engagement, relationships, meaning, and accomplishment (PERMA) profile. Social participation included activities of daily life, sports and entertainment activities, and social service activities. The independent association between each type of social participation and the components of well-being was examined by using a network analysis in both males and females. Of all 1276 participants surveyed, 60% were females. The results of the network analysis showed that positive emotion-housework (0.263), positive emotion-games (0.102), engagement-housework (0.107), engagement-work (0.054), and meaning-socializing (0.085) had unique connections in males; the average predictability in the network was 0.417. For females, positive emotion-physical activity (0.102), engagement-associations or societies (0.071), relationships-physical (0.090), relationships-socializing (0.092), and relationships-volunteering activities (0.133) had significant connections; the average predictability in the network was 0.358. Different types of social participation may have different effects on the components of well-being. Furthermore, differences according to sex in the relationship between social participation and well-being should be considered when formulating interventions to improve well-being.

Psychological distress, emotion regulation, neuroticism, and sexual relationship on patients with temporary ejaculation failure in vitro fertilization-embryo transfer treatment.

Objective: Temporary ejaculation failure on the oocyte retrieval day might leading interruption of the oocyte retrieval procedure. The present study aims to understand the psychosocial factor that affects men with temporary ejaculation failure (TEF) in Vitro fertilization-embryo transfer (IVF-ET) patients, and thus provide new ideas for optimal clinical treatment. Study design: In a prospective study, the male patients during IVF treatment in a reproductive center of a tertiary hospital in Shandong were divided into two groups, 70 men with TEF and 79 normal controls. General population sociology and clinical disease were investigated, and the Kessler 10 scale, emotion regulation questionnaire, big five inventory questionnaire, and sex subscale of marriage quality were used to assess the psychological distress, emotion regulation, neuroticism, and satisfaction with sexual life. Results: The scores of perceived distress and neuroticism of the TEF group were higher than the non-TEF group (p < 0.001), and cognitive reappraisal and sexual relationship were significantly lower than those in the non-TEF group (p < 0.001). Psychological distress (OR 1.130, p = 0.031) and neuroticism (OR 1.096, p = 0.050) were risk factors for TEF, while cognitive reappraisal (OR 0.883, p = 0.004) and sexual relationship (OR 0.712, p < 0.001) was protective factors. Conclusion: The present study demonstrates that psychosocial factors influence TEF in IVF-ET patients, which provides the basis for the prevention of the occurrence of TEF in a male undergoing IVF-ET.

IAP-1 promoted cisplatin resistance in nasopharyngeal carcinoma via inhibition of caspase-3-mediated apoptosis.

Recurrent/metastatic nasopharyngeal carcinoma (NPC) is known for having a poor prognosis due to its unfavorable response to chemoradiotherapy. However, the specific processes involved remain poorly understood. This study focused on the cisplatin-resistance mechanism in NPC to help understand the occurrence of advanced NPC and aims to explore the potential therapeutic target for cisplatin-resistant NPC. Two cisplatin-resistant NPC cell lines, HNE-1/DDP and CNE-2/DDP, were established and the differentially expressed genes (DEGs) between parental and cisplatin-resistance cell lines, filtering from high-throughput sequencing results, were analyzed. Next, the effects of IAP-1 on cisplatin-resistant nasopharyngeal cancer cell proliferation, apoptosis, drug resistance and associated cell signaling were evaluated in vitro and in vitro. From our bioinformatic results, more than 15,000 differentially expressed genes (DEGs) were found between parental and resistant cell lines. Nine related DEGs were found in the classic platinum resistance pathway, three of which (ATM, IAP-1, and IAP-2) also appeared in the top five differentially expressed pathways, with elevated IAP-1 showing the highest fold change. Further studies revealed that high IAP-1 expression can lead to an increased cisplatin inhibitory concentration and apoptosis inhibition. IAP-1 silencing can induce upregulation of the caspase-3 and enhance the antiproliferation and proapoptotic effects of cisplatin. Clinical data also showed that IAP-1 overexpression was associated with a worse survival status. In summary, in vitro and in vivo experiments demonstrated that IAP-1 plays a vital role in cisplatin resistance by regulating caspase induced apoptosis and serve as a potential novel therapeutic target and a prognostic indicator for advanced NPC.

A Potential Role for the Gsdf-eEF1α Complex in Inhibiting Germ Cell Proliferation: A Protein-Interaction Analysis in Medaka (Oryzias latipes) From a Proteomics Perspective.

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in the mature medaka testis. As for the interaction with transforming growth factor ß-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired yeast 2-hybrid assay. Coimmunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastructural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (transforming growth factor ß) and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA, which may be fundamentally conserved across the phyla during sexual differentiation.

Endolymphatic sac tumor: case report and literature review.

BACKGROUND: Endolymphatic sac tumor (ELST) is one of neuroectodermal tumor which arising from endolymphatic sac and duct. It is actually quite rare, with less than 200 cases reported. Although ELST presents benign appearance in histopathology, it can present aggressive destructive behavior in clinical. The cornerstone of treatment for ELST is complete surgical excision. However, it is almost impossible to completely resect the advanced stage tumor. There is still controversy about other treatments, such as radiotherapy and gamma knife surgery. CASE PRESENTATION: A 47-year-old man was admitted in The First Affiliated Hospital of Fujian Medical University with a 7-year history of progressive hearing loss and near 6-month repeated attacks of headache. Preoperative CT revealed a massive intracranial lesion and associated hydrocephalus. MR scanning demonstrated a 7.2 cm × 4.6 cm × 4.2 cm bulky mass located in left-sided posterior cranial fossa and temporo-occipital region which showed hyperintensity on T1-weighted images and mixed signal intensity on T2-weighted images. There was no neither clinical manifestation nor family history of Von Hippel-Lindau syndrome (VHL).Due to the mass that was large and invading the bone of skull base, it was difficult to extirpate surgically, so the ventriculoperitoneal shunt combined with local biopsy was performed. The postoperative pathology and immunohistochemical findings confirmed the lesion was an endolymphatic sac tumor. After operation, the patient regularly received radiotherapy. CONCLUSION: The widely accepted management of ELST is complete surgical resection. However, it is difficult for surgeons to achieve radical resection with late-stage ELST. Currently, there is much dispute about the role of radiotherapy for the management of ELST in academic circles. In this case where the mass cannot be surgical removed, radiotherapy has the curative effect for ELST in terms of disease control and quality of life.

A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer.

Our previous study indicated that intravenous vitamin C (IVC) treatment concurrent with modulated electrohyperthermia (mEHT) was safe and improved the quality of life (QoL) of non-small-cell lung cancer (NSCLC) patients. The aim of this trial was to further verify the efficacy of the above combination therapy in previously treated patients with refractory advanced (stage IIIb or IV) NSCLC. A total of 97 patients were randomized to receive IVC and mEHT plus best supportive care (BSC) (n = 49 in the active arm, receiving 1 g/kg * d IVC concurrently with mEHT, three times a week for 25 treatments in total) or BSC alone (n = 48 in the control arm). After a median follow-up of 24 months, progression-free survival (PFS) and overall survival (OS) were significantly prolonged by combination therapy compared to BSC alone (PFS: 3 months vs 1.85 months, P < 0.05; OS: 9.4 months vs 5.6 months, P < 0.05). QoL was significantly increased in the active arm despite the advanced stage of disease. The 3-month disease control rate after treatment was 42.9% in the active arm and 16.7% in the control arm (P < 0.05). Overall, IVC and mEHT may have the ability to improve the prognosis of patients with advanced NSCLC.

A Retrospective Study of Gemcitabine and Carboplatin With or Without Intravenous Vitamin C on Patients With Advanced Triple-Negative Breast Cancer.

Background: This is a retrospective study to examine the effect of chemotherapy with or without intravenous vitamin C (IVC) on women with advanced triple-negative breast cancer (TNBC). Methods: From 2008 to 2016, a total of 113 patients with pathologically confirmed TNBC at Clifford Hospital were evaluated, and 70 patients were matched and divided into IVC (treatment group) and non-IVC groups (control group). The match was according to age, menopausal status, and metastatic sites. In the control group, 35 patients received gemcitabine and carboplatin. In the treatment group, 35 patients received the same chemotherapy plus IVC. Results: Baseline characteristics were not significantly different between the 2 groups. According to the criteria of RECIST 1.1 (Response Evaluation Criteria in Solid Tumors), enhanced computed tomography scan was compared after 2 cycles of chemotherapy. In the treatment group, 2/35 cases had a complete remission (CR), 15/35 cases had partial remission (PR), and 13/35 cases had stable disease (SD). The response rate was 48.6%. In the control group, there were no CR cases, 14/35 cases had PR, 14/35 cases had SD, and the response rate was 40.0% (P > .05). The median progression-free survival time and median overall survival time was 7 months (95% confidence interval [CI] =1.5-28.5 months) and 27 months (95% CI = 4-40 months) in the treatment group compared with 4.5 months (95% CI = 1.5-8 months) and 18 months (95% CI = 3-26 months) in the control group (P < .05). All patients experienced diverse reactions in the gastrointestinal tract and myelosuppression. The incidence of adverse reactions in the treatment group was significantly lower than that of the control group (P < .05). Conclusion: IVC may have an effect on improving the prognosis of patients with advanced TNBC.

A mobile app implementing the international classification of functioning, disability and health rehabilitation set.

BACKGROUND: The Chinese assessment standards of the International Classification of Functioning, Disability and Health Rehabilitation Set is available now. It is coming to be used as a basic functional evaluation tool in China. With data accumulating, a mobile application is needed to eliminate the extra cost of data entry, storage, and graphical presentation of trends. This study aimed to design, develop and test a mobile app based on the International Classification of Functioning, Disability and Health Rehabilitation Set Rehabilitation Set. METHODS: The study had three phases. The first involved specifying the functional requirements of the app. Then an app was designed and refined to meet those requirements. In a pilot test, the app was used by rehabilitation professionals in clinical practice and their comments were collected for its further modification in one-on-one interviews. RESULTS: The app met the initial requirements, and the pilot study showed it worked as designed. The pilot study also showed that the app is user-friendly and convenient to use in rehabilitation practice. Some feedback was given to improve the app. CONCLUSION: An Android mobile app implementing the International Classification of Functioning, Disability and Health Rehabilitation Set was successfully developed.

Comparing polyvalent bacteriophage and bacteriophage cocktails for controlling antibiotic-resistant bacteria in soil-plant system.

Antibiotic resistant pathogenic bacteria (ARPB) residual in soil-plant system has caused serious threat against public health and environmental safety. Being capable of targeted lysing host bacteria, phage therapy has been proposed as promising method to control the ARPB contamination in environments. In this study, microcosm trials were performed to investigate the impact of various phage treatments on the dissipation of tetracycline resistant Escherichia coli K-12 and chloramphenicol resistant Pseudomonas aeruginosa PAO1 in soil-carrot system. After 70 days of incubation, all the four phage treatments significantly decreased the abundance of the pathogenic bacteria and the corresponding antibiotic resistance genes (tetW and cmlA) in the soil-carrot system (p < 0.05), following the order of the cocktail phage treatment (phages ΦYSZ1 + ΦYSZ2) > the polyvalent phage (ΦYSZ3 phage with broad host range) treatment > host-specific phage (ΦYSZ2 and ΦYSZ1) treatments > the control. In addition, the polyvalent phage treatment also exerted positive impact on the diversity and stability of the bacterial community in the system, suggesting that this is an environmentally friendly technique with broad applications in the biocontrol of ARPB/ARGs in soil-plant system.

Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells.

Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues. However, the association of LDHA levels with glioma clinical grades and the possible mechanisms of LDHA in GBM progression have not been investigated. The present study showed that there is a significant positive correlation between LDHA expression levels and tumor clinical stages. The knockdown of LDHA inhibited cell growth by inhibiting cell cycle progression and inducing apoptosis in glioma cell lines. Upon investigating the molecular mechanism, LDHA knockdown via siRNA treatment was associated with decreased cyclin D1 expression, increased cleavage of PARP, and altered B-cell lymphoma 2 and B-cell lymphoma 2-associated protein X expression. In addition, LDHA knockdown led to the marked downregulation of matrix metalloproteinase (MMP)-2, MMP-9, VE-Cadherin and vascular endothelial growth factor expression levels. Furthermore, knock down of LDHA enhanced the chemosensitivity of glioma cells to temozolomide (TMZ), a second-generation alkylating agent with activity against recurrent high-grade glioma. These findings support LDHA as a novel target for developing effective therapeutic strategies to treat GBM.